Search

Cisplatin commonly used as a chemotheropotic agent however, it is associated with numerous side effects such as reproductive cytotoxicity. It causes spermatogenic cell death and DNA damage in spermatozoa via the formation of reactive oxygene species. Resveratrol (3,5,4'-trans-trihydroxystilbene), a natural phytoalexin, is a potent antioxidant agent, present in a wide variety of dietary sources including grapes, plums and peanuts. The aim of present study to evaluate the beneficial effects of resveratrol on cisplatin induced testis damage. Male Sprague Dawley rats were used in the study and four experimental groups were formed as: 1- saline applied control, 2- resveratrol applied control, 3- cisplatin and 4- cisplatin+resveratrol groups. Following a single dose of cisplatin (7 mg/kg i.p.), either saline or resveratrol (10 mg/kg, orally) was administered for 5 days. Testis samples were prepared for histopathological and ultrastructural evaluations, cell proliferation and apoptosis. Tissue malondialdehyde (MDA), glutathione (GSH) levels and myeloperoxidase (MPO) activity were determined biochemically. Degenerated and atrophic tubules of tissue, apoptotic cells, MDA level and MPO activity were increased although proliferation index and GSH level were decreased in cisplatin group. Degenerated tight junctions between the Sertoli cells and vacuole formation in germinal epithelial cells were also revealed at this group. However, resveratrol treatment reduced degenerated and atrophic tubules, apoptotic cells, vacuole formation in germinal epithelial cells, MDA level and MPO activity and increased proliferation index and GSH level in testis. These results showed that resveratrol ameliorates cisplatin induced testis injury by the impairment of oxidative stress and apoptosis. [ABSTRACT FROM AUTHOR]

Epidemiological studies have shown that regular exercise and increased aerobic fitness are associated with a decrease in allcause mortality and morbidity, including diseases related with high blood pressure. However, whether exercise has an antiinflammatory impact on the pathogenesis of hypertension was not elucidated yet. In the present study, to investigate the potential protective and therapeutic effects of exercise training (swimming for 30 min/day, 5 days/week for 9 weeks) on renovascular hypertension (RVH) 10-week-old male Wistar albino rats were divided into 4 groups as sham-operated sedentary control group, sedentary group with RVH (2-Kidney, 1-Clip Goldblatt) and two exercised RVH groups, which had 9-week training either before the surgery or after the surgery. Systolic blood pressures (SBP) were measured by the tail-cuff method on a weekly basis and at the end of 12 weeks, rats were decapitated to obtain kidneys. SBP were significantly higher in the sedentary RVH group than the control group, whereas in the trained RVH group measurements were not different than those of the control animals. In the renal tissues of the sedentary RVH group, malondialdehyde and myeloperoxidase levels were increased with a concomitant decrease in glutathione levels, while in the trained RVH group the levels were not different than those of the control group. Moreover, in the trained RVH group, superoxide dismutase and catalase levels measured as antioxidant parameters, were also significantly increased as compared with those of the sedentary RVH group. Current results demonstrate that regular moderate training controls high blood pressure in RVH, while RVH-induced oxidative damage in renal tissue is ameliorated through the modulation of oxidant-antioxidant balance. Exercise training does not only improve the circulatory functions, but it also initiates an anti-inflammatory process to defend against the angiotensin-II-induced renal injury. [ABSTRACT FROM AUTHOR]

Chronic renal failure (CRF) is associated with oxidative stress that promotes production of reactive oxygen species and cytokine release. We aimed to investigate the possible protective and antioxidant effects of aqueous garlic extract (AGE) in a rat model of CRF. Male Sprague-Dawley rats were randomly assigned as either CRF group with 5/6 reduction in the renal mass or sham-operated control group. CRF group received either saline or AGE (250 mg/kg/day/1 mL) orally for 3 weeks. At the end of the 3 weeks, rats were decapitated and trunk blood was collected. Creatinine, blood urea nitrogen (BUN) and lactate dehydrogenase (LDH) activity, and TNF-αα and IL-1ββ levels were measured in the serum samples, while malondialdehyde (MDA), glutathione (GSH) levels, and myeloperoxidase (MPO) activity were determined in the kidney, lung, and heart samples. CRF caused significant decreases in tissue GSH, which were accompanied with significant increases in MDA levels and MPO activities, while the circulating levels of the LDH activity, creatinine, BUN, TNF-αα, and IL-1ββ were elevated. AGE treatment alleviated CRF-induced oxidative changes in the injured tissues, while CRF-induced elevations in the blood levels of the pro-inflammatory cytokines and LDH were reduced. In conclusion, CRF-induced oxidative tissue injury occurs via the activation of pro-inflammatory mediators and by neutrophil infiltration into tissues and that the protective effects of garlic on CRF-induced injury can be attributed to its ability to inhibit neutrophil infiltration and pro-inflammatory mediators. These findings suggest that garlic, as a supplementary to diet, may have a potential therapeutic use in delimitating the systemic oxidant effects of CRF on remote organs. [ABSTRACT FROM AUTHOR]

The hormone melatonin (5-methoxy-N-acetyltryptamine) is synthesized primarily in the pineal gland and retina, and in several peripheral tissues and organs. The endogenous rhythm of secretion is generated by the suprachiasmatic nuclei and entr ained by the light and dark cycle. It helps regulate other hormones and maintains the body's circadian rhythm. Melatonin is ubiquitously distributed and because of its small size and amphiphilic nature it is able to reach easily all cellular and subcellular compartments. It is a natural occurring compound with well-known antioxidant properties and has been proven as a powerful cytostatic drug in vitro as well as in vivo. The efficacy of melatonin has been assessed as a treatment of ocular diseases, blood diseases, gastrointestinal tract diseases, cardiovascular diseases, diabetes, rheumatoid arthritis, fibromyalgia, chronic fatigue syndrome, infectious diseases, neurological diseases, sleep disturbances, aging and depression. This review summarizes the pharmacokinetic properties and physiologic and pharmacological effects of melatonin [ABSTRACT FROM AUTHOR]

In this study the role of free radicals in naphthalene-induced toxicity and the protection by erdosteine are investigated. Female Sprague-Dawley rats were treated with a single oral dose of 1100 mg naphthalene/kg in corn oil. Erdosteine was given 50 mg/kg/day orally for 3 days before naphthalene treatment and rats were decapitated 24 hours after naphthalene administration. Liver and kidney tissue samples were taken for determination of malondialdehyde (MDA), glutathione (GSH), Na+, K+-ATPase and myeloperoxidase (MPO) activities. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN) and creatinine levels and lactate dehydrogenase (LDH) activity were measured in the serum samples, while TNF-α, IL-1β, IL-6, 8-hydroxy-2'-deoxyguanosine (8- OHdG) and total antioxidant capacity (AOC) were assayed in plasma samples. Naphthalene administration caused a significant decrease in tissue GSH levels, Na+, K+-ATPase activity and plasma AOC levels, which was accompanied with significant increases in tissue MDA levels and MPO activity. Moreover the pro-inflammatory mediators (TNF-α, IL-β, IL-6), 8- OHdG, LDH activity, AST, ALT, creatinine and BUN levels were significantly increased in the naphthalene group. On the other hand erdosteine treatment prevented all these biochemical changes induced by naphthalene. In conclusion, it seems likely that erdostein protects tissues by inhibiting neutrophil infiltration, balancing the oxidant-antioxidant status and regulating the generation of inflammatory mediators. [ABSTRACT FROM AUTHOR]

The impact of sex dimorphism on chronic renal failure (CRF)-induced oxidative multiorgan damage and the effects of estradiol (E2) loss and E2 supplementation on the progress of CRF were studied. Sprague-Dawley rats underwent 5/6 nephrectomy (CRF), and a group of female rats had bilateral ovariectomy (OVX), while the sham-operated rats had no nephrectomy or OVX. Rats received either estradiol propionate (50 μg/kg/day) or vehicle for six weeks. Serum BUN levels were elevated in both male and female CRF groups treated with vehicle, while creatinine level was not significantly changed in the female CRF group. CRF-induced elevation in serum TNF-α of male rats was abolished when the animals were treated with E2, while OVX exaggerated TNF-α response. In OVX and male rats with CRF, E2 treatment reversed the malondialdehyde elevations in all the studied tissues (kidney, heart, lung, ileum, brain, liver, and gastrocnemius muscle), while depletion of glutathione in these tissues was prevented by E2 treatment. Similarly, increased levels of myeloperoxidase activity, lucigenin chemiluminescence, and collagen in most of the tissues were reversed by E2 treatment. The findings show that the extent of tissue injuries was relatively less in females, while ovariectomy exacerbated all the indices of oxidative injury. Moreover, the administration of E2, with its potent anti-oxidant and anti-inflammatory effects, markedly improved CRF-induced systemic inflammatory outcomes in both male and female rats by depressing tissue neutrophil infiltration and modulating the release of inflammatory cytokines. [ABSTRACT FROM AUTHOR]

Introduction. Oxygen free radicals are involved in pathophysiology of ischemia/reperfusion (I/R) injury. This study was designed to assess the possible protective effect of pycnogenol (PYC) against I/R-induced oxidative renal damage. Materials and methods. Wistar albino rats were unilaterally nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 3 h of reperfusion. PYC (10 mg kg-1, i.p.) or saline was administered at 15 min prior to ischemia and immediately before the reperfusion period. At the end of the 3 h, rats were decapitated and trunk blood was collected. Creatinine, blood urea nitrogen (BUN), and lactate dehydrogenase (LDH) activity were measured in the serum samples, while proinflammatory cytokines, TNF-α, IL-1β, and IL-6 levels were assayed in plasma samples. Kidney samples were taken for the determination of tissue malondialdehyde (MDA), glutathione (GSH) levels, Na+,K+-ATPase, and myeloperoxidase (MPO) activities, and the extent of tissue injury was analyzed microscopically. Results. Ischemia/reperfusion caused a significant decrease in tissue GSH level and Na+,K+-ATPase activity, which was accompanied with significant increases in the renal MDA level and MPO activity. Similarly, serum creatinine and BUN levels, as well as LDH and IL-1β, IL-6, and TNF-α levels, were elevated in the saline-treated I/R group as compared to saline-treated control group. On the other hand, PYC treatment reversed all these biochemical indices, as well as histopathological alterations that were induced by I/R. Conclusions. Findings of the present study suggest that pycnogenol exerts renoprotective effects, via its free radical scavenging and antioxidant activities, that appear to involve the inhibition of tissue neutrophil infiltration. [ABSTRACT FROM AUTHOR]

Sprague Dawley rats of both sexes were injected with either saline or RVT (10 mg/kg) either before or after acetic acid ulcer induction and decapitated 3, 5 or 10 days after ulcer. In the saline-treated ulcer groups, macroscopically evident ulcers were observed, while RVT-pretreated or RVT-treated groups had lower macroscopic ulcer scores. Likewise, the microscopic damage scores were lower for the RVT-administered groups. Gastric myeloperoxidase activity, malondialdehyde, collagen and tumour necrosis factor-alpha levels, as well as luminol- and lucigenin-enhanced chemiluminescence levels that were elevated in the saline-administered ulcer groups, were depressed with both RVT-pretreatment and RVT-treatment. Moreover, depleted glutathione levels in the ulcer groups were increased back to control levels by both pre- and post-treatments of RVT. Results demonstrate that resveratrol has both protective and therapeutic effects on oxidative gastric damage by suppressing pro-inflammatory cascades, including the activation of pro-inflammatory cytokines, accumulation of neutrophils and release of oxygen-derived free radicals. [ABSTRACT FROM AUTHOR]

Abstract: Background: Reactive oxygen species and oxidative stress are implicated in hepatic stellate cell activation and liver fibrosis, which are initiated by recruitment of inflammatory cells and by activation of cytokines. Objective: The possible anti-oxidant and anti-inflammatory effects of ghrelin were evaluated in a hepatic fibrosis model in rats with bile duct ligation (BDL). Methods: Under anesthesia, bile ducts of Sprague Dawley rats were ligated, and half of the rats were subcutaneously administered with ghrelin (10 ng/kg/day) and the rest with saline for 28 days. Sham-operated control groups were administered saline or ghrelin. On the 28th day of the study, rats were decapitated and malondialdehyde (MDA) content – an index of lipid peroxidation, and myeloperoxidase (MPO) activity – an index of neutrophil infiltration – were determined in the liver tissues. Oxidant-induced tissue fibrosis was determined by collagen contents, while the hepatic injury was analyzed microscopically. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels and lactate dehydrogenase (LDH) levels were determined to assess liver function and tissue damage, respectively. Pro-inflammatory cytokines; TNF-α, IL-1β and IL-6 were also assayed in plasma samples. Results: In the saline-treated BDL group, hepatic MDA levels, MPO activity and collagen content were increased (p <0.001), suggesting oxidative organ damage, as confirmed histologically. In the ghrelin-treated BDL group, however, all of the oxidant responses were reversed significantly (p <0.05–p<0.001). Serum AST, ALT, LDH levels, and cytokines were elevated in the BDL group as compared to the control group, while this increase was significantly decreased by ghrelin treatment. Conclusion: Owing to the anti-inflammatory and anti-oxidant effect as demonstrated in our study, it is possible to speculate that exogenously administered ghrelin may possess an antifibrotic effect against biliary obstruction-induced liver fibrosis. Thus, it seems likely that ghrelin may be of potential therapeutic value in protecting the liver fibrosis and oxidative injury due to biliary obstruction. [Copyright &y& Elsevier]

Abstract: Antioxidant therapy may be useful in diseases with impaired oxidant–antioxidant balance such as pulmonary fibrosis. This study was designed to examine the effects of resveratrol, an antioxidant agents, against bleomycin-induced pulmonary fibrosis and oxidative damage. Wistar albino rats were administered a single dose of bleomycin (5mg/kg; via the tracheal cannula) followed by either saline or resveratrol (10mg/kg; orally) for 14 days. The effect of resveratrol on pulmonary oxidative damage was studied by cell count and analysis of cytokine levels (TGF-β, TNF-α, IL-1β and IL-6) in the bronchoalveolar lavage fluid (BALF) and biochemical measurements of malondialdehyde (MDA), an end product of lipid peroxidation; glutathione (GSH), a key antioxidant; and myeloperoxidase (MPO) activity, an index of neutrophil infiltration, in the lung tissue. Bleomycin-induced lung fibrosis was determined by lung collagen contents and also microscopically. Bleomycin caused a significant decrease in lung GSH, which was accompanied with significant increases in MDA level, MPO activity, and collagen contents of the lung tissue concomitant with increased levels of the pro-inflammatory mediators and cell count in BALF. On the other hand, resveratrol treatment reversed all these biochemical indices as well as histopathological alterations induced by bleomycin. The results demonstrate the role of oxidative mechanisms in bleomycin-induced pulmonary fibrosis, and resveratrol, by its antioxidant properties, ameliorates oxidative injury and fibrosis due to bleomycin. Thus, an effective supplement with resveratrol as an adjuvant therapy may be a very promising agent in alleviating the side effects of bleomycin, an effective chemotherapeutic agent. [Copyright &y& Elsevier]

Abstract: Severe burn induces the activation of an inflammatory cascade that contributes to the development of subsequent immunosuppression, increased susceptibility to sepsis, as well as generation of reactive oxygen radicals and lipid peroxidation, leading to multiple organ failure. In the present study, we investigated whether rosiglitazone, a peroxisome proliferator-activated receptor-gamma (PPAR-γ) ligand is protective against burn-induced remote organ injury. Under brief ether anaesthesia, shaved dorsum of the rats were exposed to 90°C (burn group) or 25°C (control group) water bath for 10s. Rosiglitazone (4mg/kg) or saline was administered intraperitoneally immediately after and at the 12th hour of the burn. Rats were decapitated 24h after injury and the tissue samples from lung, liver, and kidney were taken for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen contents. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels, and creatinine, blood urea concentrations (BUN) were determined to assess liver and kidney function, respectively. Serum levels of tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1β) and lactate dehydrogenase (LDH) were also assayed. Severe skin scald injury (30% of total body surface area) caused a significant decrease in GSH level, and significant increases in MDA level, MPO activity and collagen content of tissues. Similarly, serum ALT, AST and BUN levels, as well as LDH, IL-1β and TNF-α were elevated in the burn group as compared to the control group. Rosiglitazone treatment reversed all these biochemical indices. According to the findings of the present study, rosiglitazone possesses a anti-inflammatory effect that prevents burn-induced damage in remote organs and protects against organ damage. [Copyright &y& Elsevier]

Abstract: Chronic renal failure (CRF) is associated with oxidative stress that promotes production of reactive oxygen species and cytokine release. We aimed to investigate the possible protective effect of montelukast, a CysLT1 receptor antagonist, against oxidative damage in a rat model of CRF, induced by 5/6 reduction of renal mass. Male Wistar albino rats were randomly assigned to either the CRF group or the sham-operated control group, which received saline or montelukast (10mg/kg, i.p.) for 4 weeks. At the end of the 4 weeks, rats were decapitated and trunk blood was collected. Creatinine, blood urea nitrogen and lactate dehydrogenase (LDH) activity were measured in the serum samples, while leukotriene B4, TNF-α, IL-1β, IL-6, total antioxidant capacity (AOC) and leukocyte apoptosis were assayed in plasma samples. Kidney, lung, heart and brain tissue samples were taken for the determination of tissue malondialdehyde (MDA), glutathione (GSH) levels, and myeloperoxidase (MPO) activity. Oxidant-induced tissue fibrosis was determined by tissue collagen contents, and the extent of tissue injuries was analyzed microscopically. CRF caused significant decreases in tissue GSH and plasma AOC, which were accompanied with significant increases in MDA levels, MPO activities, and collagen contents of all the studied tissues, while the circulating levels of the pro-inflammatory mediators, LDH activity, creatinine and BUN were elevated. Montelukast treatment reversed all these biochemical indices, as well as histopathological alterations induced by CRF. Similarly, flow cytometric measurements revealed that leukocyte apoptosis was increased in CRF group, while montelukast reversed this effect. In conclusion, CRF-induced oxidative tissue injury occurs via the activation of pro-inflammatory mediators and by neutrophil infiltration into tissues, and that protective effects of montelukast on CRF-induced injury can be attributed to its ability to inhibit neutrophil infiltration and apoptosis, to balance oxidant-antioxidant status and to regulate the generation of pro-inflammatory mediators. [Copyright &y& Elsevier]

Abstract: Aim: Oxytocin was previously shown to have anti-inflammatory effects in different inflammation models. The major objective of the present study was to evaluate the protective role of oxytocin (OT) in protecting the kidney against ischemia/reperfusion (I/R) injury. Materials and methods: Male Wistar albino rats (250–300 g) were unilaterally nephrectomized, and subjected to 45 min of renal pedicle occlusion followed by 6 h of reperfusion. OT (1 mg/kg, ip) or vehicle was administered 15 min prior to ischemia and was repeated immediately before the reperfusion period. At the end of the reperfusion period, rats were decapitated and kidney samples were taken for histological examination or determination of malondialdehyde (MDA), an end product of lipid peroxidation; glutathione (GSH), a key antioxidant; and myeloperoxidase (MPO) activity, an index of tissue neutrophil infiltration. Creatinine and urea concentrations in blood were measured for the evaluation of renal function, while TNF-α and lactate dehydrogenase (LDH) levels were determined to evaluate generalized tissue damage. Formation of reactive oxygen species in renal tissue samples was monitored by chemiluminescence technique using luminol and lucigenin probes. Results: The results revealed that I/R injury increased (p <0.01–0.001) serum urea, creatinine, TNF-α and LDH levels, as well as MDA, MPO and reactive oxygen radical levels in the renal tissue, while decreasing renal GSH content. However, alterations in these biochemical and histopathological indices due to I/R injury were attenuated by OT treatment (p <0.05–0.001). Conclusions: Since OT administration improved renal function and microscopic damage, along with the alleviation of oxidant tissue responses, it appears that oxytocin protects renal tissue against I/R-induced oxidative damage. [Copyright &y& Elsevier]

Abstract: Mercury(II) is a highly toxic metal which induces oxidative stress in the body. In this study we aimed to investigate the possible protective effect of Ginkgo biloba (EGb), an antioxidant agent, against experimental mercury toxicity in rat model. Following a single dose of 5mg/kg mercuric chloride (HgCl2; Hg group) either saline or EGb (150mg/kg) was administered for 5days. After decapitation of the rats trunk blood was obtained and the tissue samples from the brain, lung, liver, and kidney were taken for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen contents. Formation of reactive oxygen species in the tissue samples was monitored by chemiluminescence (CL) technique. BUN, creatinin, ALT, and AST levels and tumor necrosis factor-α (TNF-α) and lactate dehydrogenase (LDH) activity were assayed in serum samples. The results revealed that HgCl2 induced oxidative damage caused significant decrease in GSH level, significant increase in MDA level, MPO activity and collagen content of the tissues. Treatment of rats with EGb significantly increased the GSH level and decreased the MDA level, MPO activity, and collagen contents. Similarly, serum ALT, AST and BUN levels, as well as LDH and TNF-α, were elevated in the Hg group as compared to control group. On the other hand, EGb treatment reversed all these biochemical indices. Our results implicate that mercury-induced oxidative damage in brain, lung, liver, and kidney tissues protected by G. biloba extract, with its antioxidant effects. [Copyright &y& Elsevier]

Oxidative stress, in particular lipid peroxidation, induces collagen synthesis and causes fibrosis. The aim of this study was to assess the antioxidant and antifibrotic effects of erdosteine on liver fibrosis induced by biliary obstruction in rats. Liver fibrosis was induced in Wistar albino rats by bile duct ligation (BDL). Erdosteine (10 mg/kg, orally) or saline was administered for 28 days. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) levels were determined to assess liver functions and tissue damage, respectively. Pro-inflammatory cytokines, TNF-α, IL-1β and IL-6 and antioxidant capacity (AOC) were assayed in plasma samples. Liver tissues were taken for determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen content. Production of reactive oxidants was monitored by chemiluminescence assay. Serum AST, ALT, LDH, and plasma cytokines were elevated in the BDL group as compared to controls and were significantly decreased by erdosteine treatment. Hepatic GSH level and plasma AOC, depressed by BDL, were elevated back to control level with erdosteine treatment. Furthermore, hepatic luminol and lucigenin chemiluminescence (CL), MDA level, MPO activity and collagen content in BDL group increased dramatically compared to control and reduced by erdosteine treatment. Since erdosteine administration alleviated the BDL-induced oxidative injury of the liver and improved the hepatic functions, it seems likely that erdosteine with its antioxidant and antifibrotic properties, may be of potential therapeutic value in protecting the liver fibrosis and oxidative injury due to biliary obstruction. [ABSTRACT FROM AUTHOR]

Abstract: Urinary tract infections may induce severe inflammation, transient impairment in renal function and scar formation, ranging in severity from acute symptomatic pyelonephritis to chronic pyelonephritis, which have a potential to lead to renal failure and death. The present study aimed to investigate the possible protective effect of montelukast, a selective antagonist of cysteinyl leukotriene receptor 1 (leukotriene CysLT1), against Escherichia coli-induced oxidative injury and scarring in renal tissue. Wistar rats were injected 0.1 ml of E. coli (ATCC 25922 1010 cfu/ml) or saline into left renal medullae. Six rats were assigned as the sham group and were given 0.1 ml 0.9% NaCl. Pyelonephritic rats were treated with either saline or montelukast immediately after surgery and at daily intervals. Twenty-four hours or one week after E. coli injection, rats were decapitated and the kidney samples were taken for histological examination or determination of renal malondialdehyde, glutathione (GSH) levels, myeloperoxidase (MPO) activity, and collagen contents. Formation of reactive oxygen species in renal tissue samples was monitored by using chemiluminescence technique with luminol and lucigenin probes. Creatinine, blood urea nitrogen and lactate dehydrogenase (LDH) activity were measured in the serum samples. E. coli inoculation caused significant increases in malondialdehyde level, MPO activity, chemiluminescence levels and collagen content, while GSH level was decreased in the renal tissues (p <0.05–0.001). On the other hand, serum TNF-alpha, LDH, blood urea nitrogen and serum creatinine levels were elevated in the pyelonephritic rats as compared to control group. Leukotriene CysLT1 receptor antagonist montelukast reversed all these biochemical indices, as well as histopathological alterations, that were induced by acute pyelonephritis. It seems likely that montelukast protects kidney tissue by inhibiting neutrophil infiltration, balancing oxidant–antioxidant status, and regulating the generation of inflammatory mediators suggesting a future role for leukotriene CysLT1 receptor antagonists in the treatment of pyelonephritis. [Copyright &y& Elsevier]

Regarding the mechanisms of renal scarring in pyelonephritis, several hypotheses have been put forward, among which oxidative stress is prominent. The present study investigated the possible protective effect of melatonin treatment against Escherichia coli-induced oxidative injury and scarring in renal tissue. For this purpose, 0.1 mL E. coli (ATCC 25922; 1010 colony-forming units/mL) or saline was injected directly into the renal parenchyma of Wistar rats. Pyelonephritic rats were treated with either saline or melatonin (10 mg/kg) intraperitoneally. Twenty-four hours or 1 wk after E. Coli injection, rats were decapitated and trunk blood samples were collected for BUN, creatinine, tumor necrosis factor- α (TNF- α) and lactate dehydrogenase (LDH) determination. In kidney samples, histological analysis was performed, and malondialdehyde (MDA), glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen contents were measured. Formation of reactive oxygen species was monitored using a chemiluminescence (CL) technique. Escherichia Coli inoculation caused a significant reduction in renal GSH levels, which was accompanied by significant increases in MDA levels, MPO activity, CL levels and collagen content of the renal tissues ( P < 0.05–0.001). Similarly, serum TNF- α and, LDH, BUN and creatinine levels were elevated in the pyelonephritic rats when compared with control animals. Melatonin treatment reversed all these biochemical indices, as well as histopathological alterations induced by acute pyelonephritis. The protective effects of melatonin can be ascribed to its ability to inhibit neutrophil infiltration, to balance the oxidant–antioxidant status, and to regulate the generation of inflammatory mediators, suggesting a future role for melatonin in the treatment of acute pyelonephritis. [ABSTRACT FROM AUTHOR]

Background: The present study was designed to examine whether resveratrol, a potent antioxidant, protects against renal ischemia-reperfusion (I/R) injury. Methods: Wistar albino rats were unilaterally nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 6 h of reperfusion. Resveratrol (RVT, 30 mg/kg, i.p.) or vehicle was administered twice, at 30 min prior to ischemia and immediately before the reperfusion period. At the end of the reperfusion period, rats were decapitated and kidney samples were taken for histological examination or determination of levels of renal malondialdehyde (MDA), an end product of lipid peroxidation; glutathione (GSH), a key antioxidant; and myeloperoxidase (MPO) activity, an index of tissue neutrophil infiltration. Formation of reactive oxygen species in hepatic tissue samples was monitored by using chemiluminescence (CL) technique with luminol and lucigenin probes. Renal tissue collagen content as a fibrosis marker was also determined, while serum creatinine and urea concentrations were measured for the evaluation of renal function. Tumor necrosis factor- (TNF-) and lactate dehydrogenase (LDH) were also assayed in serum samples. Results: Ischemia/reperfusion caused a significant decrease in tissue GSH level, which was accompanied by significant increases in the renal luminol and lucigenin CL values, MDA level, MPO activity and collagen content. Similarly, serum creatinine and BUN levels, as well as LDH and TNF-α, were elevated in the I/R group as compared to control group. On the other hand, resveratrol treatment reversed all these biochemical indices, as well as histopathological alterations that were induced by I/R. Conclusions: Findings of the present study suggest that resveratrol exerts renoprotective effects via its radical scavenging and antioxidant activities, which appear to involve the inhibition of tissue neutrophil infiltration. [Copyright &y& Elsevier]

Abstract: Oxidative stress has an important role in the development of multiorgan failure after major burn. This study was designed to determine the possible protective effect of experimental hypothyroidism in hepatic and gastrointestinal injury induced by thermal trauma. Sprague Dawley rats were administered saline or PTU (10mgkg−1 i.p.) for 15 days, and hypothyroidism was confirmed by depressed serum T3 and T4 concentrations. Under brief ether anesthesia, shaved dorsum of rats was exposed to 90°C (burn group) or 25°C (control group) water bath for 10s. PTU or saline treatment was repeated at the 12th hour of the burn. Rats were decapitated 24h after injury and tissue samples from liver, stomach and ileum were taken for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen contents. Formation of reactive oxygen species in tissue samples was monitored by using chemiluminescence (CL) technique with luminol and lucigenin probes. Tissues were also examined microscopically. Tumor necrosis factor (TNF)-α and lactate dehydrogenase (LDH) were assayed in serum samples. Severe skin scald injury (30% of total body surface area) caused a significant decrease in GSH level, which was accompanied with significant increases in MDA level, MPO activity, CL levels and collagen content of the studied tissues (p <0.05–0.001). Similarly, serum TNF-α and LDH were elevated in the burn group as compared to control group. On the other hand, PTU treatment reversed all these biochemical indices, as well as histopathological alterations induced by thermal trauma. Our results suggest that PTU-induced hypothyroidism reduces oxidative damage in the hepatic, gastric and ileal tissues probably due to hypometabolism, which is associated with decreased production of reactive oxygen metabolites and enhancement of antioxidant mechanisms. [Copyright &y& Elsevier]

Abstract: Methotrexate is an antifolate that is widely used in the treatment of rheumatic disorders and malignant tumors. The efficacy of methotrexate is often limited by severe side effects and toxic sequelae, where oxidative stress is noticeable. In the present study, the possible protective effect of β-glucan in methotrexate-induced toxicity was investigated. Following a single dose of methotrexate injection (20 mg/kg), either saline or β-glucan (50 mg/kg; orally) was administered for 5 days. After decapitation of the rats, trunk blood was obtained and the ileum, liver and kidney were removed to measure tissue malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen content, as well as histological examination. Methotrexate caused a significant decrease in GSH levels, while MDA levels, MPO activity and collagen content were increased in all the tissues (P <0.05–0.001). On the other hand, administration of β-glucan following methotrexate abolished the depletion of GSH and inhibited the increases in MDA, MPO activity and collagen content, while the histological analysis revealed that β-glucan attenuated the tissue damage. Stimulation index, an indicator of oxidative burst in the neutrophils, was decreased by methotrexate (P <0.001), while β-glucan abolished this effect. Furthermore, increased leukocyte apoptosis and cell death in methotrexate-treated animals were inhibited by β-glucan (P <0.05). Thus, the findings of the present study suggest that β-glucan, through its antioxidant and immunoregulatory effects, may be of therapeutic value in alleviating the leukocyte apoptosis, oxidative tissue injury and thereby the intestinal and hepatorenal side effects of methotrexate treatment. [Copyright &y& Elsevier]

Resveratrol (3,5,4′-trans-trihydroxystilbene), a natural phytoalexin, has various pharmacological effects, including anti-inflammatory properties via inhibition of oxidation, leukocyte priming, and expression of inflammatory mediators. The present study was aimed to investigate the possible beneficial activities of resveratrol on lung and kidney damage in a rat model of sepsis. Materials and methods: Sepsis was induced to Sprague–Dawley rats of both sexes (200–250 g) by cecal ligation and perforation. The rats were treated with resveratrol (30 mg/kg; i.p.) or saline after induction of sepsis and at 16 h. Twenty-four hours after the sepsis-induction, all rats were decapitated. Blood was collected for the measurement of tumor necrosis factor-α level and lactate dehydrogenase activity. Lung and kidney samples were taken for histological assessment and for the measurement of malondialdehyde, glutathione level, myeloperoxidase activity, and collagen content. Results: Sepsis caused a significant increase in malondialdehyde levels, myeloperoxidase activity, and collagen content of the lung and kidney tissues with a concomitant reduction in glutathione levels. Microscopic examination revealed severe destruction of regular morphology in both lung and kidney tissues. Serum tumor necrosis factor-α and lactate dehydrogenase levels also were higher in rats with sepsis compared to those of the sham group. Resveratrol treatment reversed these biochemical parameters and preserved tissue morphology as evidenced by histological evaluation. Conclusions: Resveratrol, a phenolic compound, reduces sepsis-induced remote organ injury, at least in part, through its ability to balance oxidant-antioxidant status, to inhibit neutrophil infiltration and to regulate the release of inflammatory mediators. [Copyright &y& Elsevier]

Abstract: Background: Oxygen free radicals are important components involved in the pathophysiological processes observed during ischemia/reperfusion (I/R). Objective: This study was designed to assess the possible protective effect of montelukast, a selective antagonist of cysteinyl leukotriene receptor 1 (CysLT1), on renal I/R injury. Methods: Wistar albino rats were unilaterally nephrectomized and subjected to 45min of renal pedicle occlusion followed by 6h of reperfusion. Montelukast (10mgkg−1, i.p.) or saline was administered at 15min prior to ischemia and immediately before the reperfusion period. At the end of the reperfusion period, following decapitation, kidney samples were taken for histological examination or for determination of renal malondialdehyde (MDA), an end product of lipid peroxidation; glutathione (GSH), a key antioxidant; and myeloperoxidase (MPO) activity, an index of tissue neutrophil infiltration. Formation of reactive oxygen species in renal tissue samples was monitored by using chemiluminescence (CL) technique with luminol and lucigenin probes. Creatinine, blood urea nitrogen and lactate dehydrogenase (LDH) activity were measured in the serum samples, while leukotriene B4, TNF-α, IL-β, IL-6 and total antioxidant capacity (AOC) were assayed in plasma samples. Results: Ischemia/reperfusion caused a significant decrease in renal GSH and plasma AOC, which was accompanied with significant increases in MDA level, MPO activity, and CL levels of the renal tissue concomitant with increased levels of the pro-inflammatory mediators, LDH activity, creatinine and BUN. On the other hand, montelukast treatment reversed all these biochemical indices as well as histopathological alterations induced by I/R. Conclusions: CysLT1 receptor antagonist montelukast reversed I/R-induced oxidant responses, improved microscopic damage and renal function. It seems likely that montelukast protects kidney tissue by inhibiting neutrophil infiltration, balancing oxidant–antioxidant status, and regulating the generation of inflammatory mediators. [Copyright &y& Elsevier]

Abstract: The aim of this study was to assess the antioxidant and antifibrotic effects of chronic administration of 2-mercaptoethane sulfonate (MESNA) on oxidative liver damage and fibrosis induced by biliary obstruction in rats. Liver fibrosis was induced in male Wistar albino rats by bile duct ligation and scission (BDL). MESNA (150mg/kg, i.p.) or saline was administered for 28 days. At the end of the experiment, rats were killed by decapitation. Serum aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels were determined to assess liver function. Tumor necrosis factor-alpha (TNF-α) and lactate dehidrogenase (LDH) were also assayed in serum samples. Liver tissues were taken for determination of the free radicals, hepatic malondialdehyde (MDA) levels, an end product of lipid peroxidation; glutathione (GSH) levels, a key antioxidant; myeloperoxidase (MPO) activity, as an indirect index of neutrophil infiltration. Hepatic collagen content, as a fibrosis marker was also determined. Serum AST, ALT, LDH and TNF-α levels were elevated in the BDL group as compared to control group, while this increase was significantly decreased by MESNA treatment. BDL caused a significant (p <0.05–0.001) decrease in GSH levels while MDA levels and MPO activity were increased in the liver tissue. These changes were reversed by MESNA treatment. Collagen contents of the liver tissue was increased by BDL (p <0.001), and reversed back to the control levels with MESNA. Since MESNA administration alleviated the BDL-induced oxidative injury of the liver and improved the hepatic functions, it seems likely that MESNA with its antioxidant and antifibrotic properties, may be of potential therapeutic value in protecting the liver fibrosis and oxidative injury due to biliary obstruction. [Copyright &y& Elsevier]

Abstract: Pressure ulcers (PU) cause morphological and functional alterations in the skin and visceral organs. In this study we investigated the role of oxidative damage in PUs and the probable beneficial effect of β-glucan treatment against this damage. β-glucan is known to have immunomodulatory effects. Experiments were carried on Wistar albino rats. PU was induced by applying magnets over steel plates that were implanted under the skin, to compress the skin and cause ischemia where removing the magnets cause reperfusion of the tissue. Within the first 12 h, rats were subjected to 5 cycles of ischemia/reperfusion (I/R), followed by 12 h ischemia. This protocol was repeated for 3 days. In treatment groups, twice a day during reperfusion periods, β-glucan was either applied locally (25 mg/kg) as an ointment on skin, or administered orally (50 mg/kg) as a gavage. At the end of the experimental periods, tissue samples (skin, liver, kidney, lung, stomach, and ileum) were taken for the measurement of malondialdehyde (MDA) – an index of lipid peroxidation – and glutathione (GSH) – a key antioxidant – levels. Neutrophil infiltration was evaluated by the measurement of tissue myeloperoxidase activity, while collagen contents were measured for the evaluation of tissue fibrosis. Skin tissues were also examined microscopically. Liver and kidney functions were assayed in serum samples. Local treatment with β-glucan inhibited the increase in MDA and MPO levels and the decrease in GSH in the skin induced by PU, but was less efficient in preventing the damage in visceral organs. However, systemic treatment prevented the damage in the visceral organs. Significant increases in creatinine, BUN, ALT, AST, LDH and collagen levels in PU group were prevented by β-glucan treatment. The light microscopic examination exhibited significant degenerative changes in dermis and epidermis in the PU group. Tissue injury was decreased especially in the locally treated group. Thus, supplementing geriatric and neurologically impaired patients with adjuvant therapy of β-glucan may have some benefits for successful therapy and improving quality of life. [Copyright &y& Elsevier]

Abstract: This investigation elucidates the role of free radicals in acetaminophen (AA)-induced toxicity and the possible protection by resveratrol (RVT). BALB-c mice were injected with a single dose of 900mg/kg AA to induce toxicity, while RVT administred in a dose of 30mg/kg i.p. following AA. Mice were sacrificed 4h after AA injection to determine serum ALT, AST and tumor necrosis factor-alpha (TNF-α) levels in blood, and glutathione (GSH), malondialdehyde (MDA) levels, myeloperoxidase (MPO) activity and collagen contents in liver tissues. Formation of reactive oxygen species in hepatic tissue samples was monitored by using chemiluminescence (CL) technique with luminol and lucigenin probe. ALT, AST levels and TNF-α were increased significantly after AA treatment, and reduced with RVT. AA caused a significant decrease in GSH levels while MDA levels and MPO activity were increased in liver tissues. On the other hand when RVT administered following AA, depletion of GSH and accumulation of MDA and neutrophil infiltration were reversed back to control. Furthermore increased luminol and lucigenin CL levels in the AA group reduced by RVT treatment. Our results implicate that AA causes oxidative damage in hepatic tissues and RVT, by its potent antioxidant effects protects the liver tissue. These data suggest that RVT may be of therapeutic use in preventing hepatic oxidative injury due to AA toxicity. [Copyright &y& Elsevier]

Pressure ulcers (PU) cause morphological and functional alterations in the skin and visceral organs; the damage is believed to be due to ischemia/reperfusion (I/R) injury. In this study, we examined the role of oxidative damage in PU and the beneficial effect of treatment with the antioxidant melatonin. PU were induced by applying magnets over steel plates that were implanted under the skin of rats; this compressed the skin and caused ischemia. Within a 12-hr period, rats were subjected to five cycles of I/R (2 and 0.5 hr respectively), followed by an additional 12 hr of ischemia (to simulate the period at sleep at night). This protocol was repeated for 3 days. In treatment groups, twice a day during reperfusion periods, melatonin (5 mg per rat) was either applied locally as an ointment on skin, or administered i.p. (10 mg/kg). At the end of the experimental period, blood and tissue (skin, liver, kidney, lung, stomach, and ileum) samples were taken for determination of biochemical parameters and for histological evaluation. Local treatment with melatonin inhibited the increase in malondialdehyde levels; an index of lipid peroxidation, myeloperoxidase activity; an indicator of tissue neutrophil infiltration, and the decrease in glutathione; a key antioxidant, in the skin induced by PU, but was less efficient in preventing the damage in visceral organs. However, systemic treatment prevented the damage in the visceral organs. Significant increases in creatinine, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and collagen levels in animals with PU were prevented by melatonin treatment. The light microscopic examination exhibited significant degenerative changes in dermis and epidermis in the PU rats. Tissue injury was decreased especially in the locally treated group. Findings of the present study suggest that local and/or systemic melatonin treatment may prove beneficial in the treatment of PU. [ABSTRACT FROM AUTHOR]

Abstract: The present study was designed to determine the possible protective effects of Ginkgo biloba extract (EGb) against oxidative organ damage induced by irradiation (IR). Sprague–Dawley rats were exposed to whole-body IR (800cGy) after a 15-day pretreatment with either saline or EGb (50mg/kg/day), intraperitoneally, and treatments were repeated immediately after the IR. Then the rats were decapitated at either 6h or 72h after IR, where EGb or saline injections were repeated once daily. Lung, liver, kidney and ileum samples were obtained for the determination of malondialdehyde, glutathione levels, myeloperoxidase activity and collagen contents, while oxidant-induced DNA fragmentation was evaluated in the ileal tissues. All tissues were also examined microscopically and assayed for the production of reactive oxidants using chemiluminescence (CL). Lactate dehydrogenase (LDH)-an indicator of tissue damage and TNF-α were assayed in serum samples. In the saline-treated irradiation groups, glutathione levels were decreased significantly, while the malondialdehyde levels, myeloperoxidase activity and collagen content were increased in the tissues (p <0.01–0.001), which were in parallel with the increases in luminol and lucigenin CL values. In the EGb treated-IR groups, all of these oxidant responses were prevented significantly (p <0.05–0.01). LDH and TNF-α levels, which were increased significantly (p <0.01–0.001) following IR, were decreased (p <0.05–0.001) with EGb treatment. In conclusion, the present data demonstrate that EGb, through its free radical scavenging and antioxidant properties, attenuates irradiation-induced oxidative organ injury, suggesting that EGb may have a potential benefit in enhancing the success of radiotherapy. [Copyright &y& Elsevier]

Abstract: Thermal injury may lead to systemic inflammatory response, and multiple organ failure. Generation of reactive oxygen radicals and lipid peroxidation play important roles in burn-induced remote organ injury. In the present study, we investigated the putative protective effect of local or systemic β-glucan treatment on burn-induced remote organ injury. Wistar albino rats were exposed to 90 °C bath for 10 s to induce thermal trauma. β-glucan (3.75 mg/rat locally or 50 mg/kg orally) or saline was administered immediately after the trauma and were repeated twice daily in 48 h groups. Rats were decapitated either 6 or 48 h after burn injury and the skin, lung, liver, ileum and kidney tissues were taken for the measurement of malondialdehyde (MDA) — an index of lipid peroxidation — and glutathione (GSH) — a key antioxidant — levels. Neutrophil infiltration was evaluated by the measurement of tissue myeloperoxidase (MPO) activity, while the tumor necrosis factor-α (TNF-α) levels were measured in serum samples. Skin tissues were also examined microscopically. Severe skin scald injury (30% of total body surface area) caused significant decreases in GSH levels of the liver and intestinal tissues (p <0.01–<0.001), while MDA levels were significantly (p <0.01–p <0.001) increased at post-burn 6 and 48 h. Both local and systemic β-glucan treatments significantly reversed (p <0.01–p <0.001) the elevations in MDA levels, while reduced GSH levels were reversed back to control levels (p <0.01–p <0.001); and the raised MPO levels were significantly decreased (p <0.05–p <0.001). The results indicate that both systemic and local administration of β-glucan were effective against burn-induced oxidative tissue damage in the rat. β-glucans, besides their immunomodulatory effects, have additional antioxidant properties. Therefore, β-glucans merit consideration as therapeutic agents in the treatment of burn injuries. [Copyright &y& Elsevier]

Abstract: The efficacy of methotrexate (MTX), a widely used cytotoxic chemotherapeutic agent, is often limited by severe side effects and toxic sequelae. Regarding the mechanisms of these side effects, several hypotheses have been put forward, among which oxidative stress is noticeable. The present study was undertaken to determine whether taurine, a potent free radical scavenger, could ameliorate MTX-induced oxidative injury and modulate immune response. Following a single dose of methotrexate (20 mg/kg), either saline or taurine (50 mg/kg) was administered for 5 days. After decapitation of the rats, trunk blood was obtained and the ileum, liver, and kidney were removed to measure malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity, and collagen content, as well as histological examination. Our results showed that MTX administration increased the MDA, MPO activity, and collagen contents and decreased GSH levels in all tissues (P < 0.001), while these alterations were reversed in taurine-treated group (P < 0.05–0.01). Elevated (P < 0.001) TNF-α level observed following MTX treatment was depressed with taurine (P < 0.01). Oxidative burst of neutrophils stimulated by phorbol myristate acetate was reduced in saline-treated MTX group (P < 0.001), while taurine abolished this effect. Similarly, flow cytometric measurements revealed that leukocyte apoptosis and cell death were increased in MTX-treated animals, while taurine reversed these effects (P < 0.05). Reduced cellularity in bone marrow samples of MTX-treated group (P < 0.01) was reversed back to control levels in taurine-treated rats. Severe degeneration of the intestinal mucosa, liver parenchyma, glomerular, and tubular epithelium observed in saline-treated group was improved by taurine treatment. In conclusion, it appears that taurine protects against methotrexate-induced oxidant organ injury and inhibits leukocyte apoptosis and may be of therapeutic potential in alleviating the systemic side effects of chemotherapeutics. [Copyright &y& Elsevier]

Background and aim: Sepsis is commonly associated with enhanced generation of reactive oxygen metabolites, leading to multiple organ dysfunctions. The aim of this study was to examine the putative protective role of estradiol against sepsis-induced oxidative organ damage. Materials and methods: Sepsis was induced by cecal ligation and puncture method in Wistar albino rats. Sham-operated (control) and sepsis groups received saline or estradiol propionate (10 mg/kg) intraperitoneally immediately after the operation and at 12 h. Twenty-four hours after the surgery, rats were decapitated and malondialdehyde, glutathione levels, and myeloperoxidase activity were determined in the liver and ileum, while oxidant-induced tissue fibrosis was determined by collagen contents. Tissues were also examined microscopically. Serum aspartate aminotransferase, alanine aminotransferase levels, and lactate dehydrogenase were measured for the evaluation of liver functions and tissue damage, respectively. Tumor necrosis factor-α was also assayed in serum samples. Results: In the saline-treated sepsis group, glutathione levels were decreased significantly, while the malondialdehyde levels, myeloperoxidase activity, and collagen content were increased in the tissues (P &#60; 0.01 to P &#60; 0.001), suggesting oxidative organ damage, which was also verified histologically. In the estradiol-treated sepsis group, all of these oxidant responses were reversed significantly (P &#60; 0.05 to P &#60; 0.01). Liver function tests and tumor necrosis factor-α levels, which were increased significantly (P &#60; 0.001) following sepsis, were decreased (P &#60; 0.05 to P &#60; 0.001) with estradiol treatment. Conclusion: The results demonstrate the role of oxidative mechanisms in sepsis-induced tissue damage, and estradiol, by its antioxidant properties, ameliorates oxidative organ injury, implicating that treatment with estrogens might be applicable in clinical situations to ameliorate multiple organ damage induced by sepsis. [Copyright &y& Elsevier]

Abstract: There is increasing evidence to suggest that reactive oxygen metabolites (ROMs) play a role in the pathogenesis of ischemia/reperfusion injury (I/R) in the kidney. This study was designed to determine the possible protective effect of Ginkgo biloba extract (EGb) on renal ischemia/reperfusion (I/R) injury. Wistar albino rats were unilaterally nephrectomized, and 15 days later they were subjected to 45min of renal pedicle occlusion followed by 6h of reperfusion. Ginkgo biloba extract (EGb) (50mgkg−1 day−1) or saline was administered twice, 15min prior to ischemia and immediately before the reperfusion period. At the end of the treatment period, all rats were decapitated. Kidney samples were taken for histological examination or determination of the renal malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen content. Production of reactive oxidants was monitored by chemiluminescence (CL) assay. Creatinine and urea concentrations in blood were measured for the evaluation of renal function. Tumor necrosis factor-α (TNF-α) and lactate dehydrogenase (LDH) were also assayed in serum samples. Ischemia/reperfusion caused a significant decrease in GSH level, which was accompanied with significant increases in MDA level, MPO activity and collagen content of kidney tissues. Similarly, serum BUN and creatinine levels, as well as LDH and TNF-α, were elevated in the I/R group as compared to control group. On the other hand, EGb treatment reversed all these biochemical indices, as well as histopathological alterations, which were induced by I/R. The findings imply that ROMs play a causal role in I/R-induced renal injury and EGb exerts renoprotective effects probably by the radical scavenging and antioxidant activities. [Copyright &y& Elsevier]

Abstract: Sepsis leads to various organ damage and dysfunction. One of the underlying mechanisms is thought to be the oxidative damage due to the generation of free radicals. In this study, we investigated the putative protective role of β-glucan against sepsis-induced oxidative organ damage. Sepsis was induced by caecal ligation and puncture (CLP) in Wistar albino rats. Sham operated (control) and sepsis groups received saline or β-glucan (50 mg/kg, po) once daily for 10 days and 30 min prior to and 6 h after the CLP. Sixteen hours after the surgery, rats were decapitated and the biochemical changes were determined in the brain, diaphragm, kidney, heart, liver and lung tissues using malondialdehyde (MDA) content – an index of lipid peroxidation – glutathione (GSH) levels – a key antioxidant – and myeloperoxidase (MPO) activity – an index of neutrophil infiltration. Serum TNF-α levels were assessed by RIA method. Tissues were also examined under light microscope to evaluate the degree of sepsis-induced damage. The results demonstrate that sepsis significantly decreased GSH levels and increased the MDA levels and MPO activity (p &#60;0.05–p &#60;0.001) causing oxidative damage. Elevated plasma TNF-α levels in septic rats significantly reduced to control levels in β-glucan treated rats. Since β-glucan administration reversed these oxidant responses, it seems likely that β-glucan protects against sepsis-induced oxidative organ injury. [Copyright &y& Elsevier]

Abstract: Thermal injury elicits several systemic consequences, among them the systemic inflammatory response where the generation of reactive oxygen radicals and lipid peroxidation play important roles. In the present study, we investigated whether the leukotriene receptor blocker montelukast is protective against burn-induced remote organ injury. Under brief ether anaesthesia, shaved dorsum of the rats was exposed to 90°C (burn group) or 25°C (control group) water bath for 10s. Montelukast (10mg/kg) or saline was administered intraperitoneally immediately after and at the 12th hour of the burn injury. Rats were decapitated 24h after burn injury and the tissue samples from lung, liver, kidney and skin were taken for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen contents. Tissues were also examined microscopically. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels and creatinine, urea (BUN) concentrations were determined to assess liver and kidney function, respectively. Tumor necrosis factor-α (TNF-α) and lactate dehydrogenase (LDH) were also assayed in serum samples. Severe skin scald injury (30% of total body surface area) caused a significant decrease in GSH level, which was accompanied with significant increases in MDA level, MPO activity and collagen content of tissues. Similarly, serum ALT, AST and BUN levels, as well as LDH and TNF-α, were elevated in the burn group as compared to control group. On the other hand, montelukast treatment reversed all these biochemical indices, as well as histopathological alterations, which were induced by thermal trauma. Findings of the present study suggest that montelukast possesses an anti-inflammatory effect on burn-induced damage in remote organs and protects against oxidative organ damage by a neutrophil-dependent mechanism. [Copyright &y& Elsevier]

Background: Sepsis, commonly associated with enhanced generation of reactive oxygen metabolites, leads to multiple organ dysfunctions. The neurohypophyseal hormone oxytocin (OT), released during social contact, was recently shown to modulate the immune and inflammatory processes. We investigated the protective role of OT against sepsis-induced pelvic inflammation. Materials and methods: Under anesthesia, sepsis was induced in female Sprague-Dawley rats (200–250 g) by cecal ligation and perforation method. Sham-operated rats served as controls. Either saline or OT (1 mg/kg) was given subcutaneously immediately after and at the 16th hour, and rats were decapitated at the 24th hour of sepsis induction. Colon, uterus, and liver samples were obtained for the histopathological analysis of damage and for the measurement of myeloperoxidase (MPO) activity, indicating neutrophil infiltration, malondialdehyde (MDA), indicating lipid peroxidation, and glutathione (GSH), a key antioxidant, levels. Results: Colonic, uterine and liver MDA levels in the sepsis group were significantly increased (P &#60; 0.01-P &#60; 0.001), while colonic and uterine GSH levels were decreased (P &#60; 0.05-P &#60; 0.01) when compared to the control group. OT treatment reversed the MDA and GSH levels back to the control levels, while hepatic GSH levels were not altered. MPO activity in the colon and liver was increased by sepsis (P &#60; 0.05-P &#60; 0.001) while OT treatment abolished the elevated MPO activity. Collagen levels in the uterus and liver were increased by sepsis (P &#60; 0.01) and OT treatment reduced the collagen levels in both tissues (P &#60; 0.01-P &#60; 0.05). Serum TNF-α levels were significantly increased by sepsis (P &#60; 0.001) and OT treatment abolished the sepsis-induced increase in TNF-α levels. Conclusions: OT protects against sepsis-induced oxidative damage by acting as an antioxidant agent and its protective effect in the colon and liver appears to be dependent on its inhibitory effect on neutrophil infiltration. Our results suggest that OT may have a therapeutic value in limiting sepsis-associated multiple organ damage. [Copyright &y& Elsevier]

Abstract: Sepsis is a generalized inflammatory response, which involves organ systems remote from the locus of the initial infectious insult, accompanied by the release of cytokines and the subsequent formation of reactive oxygen and nitrogen species. The aim of this study was to investigate the possible protective effect of octreotide (OCT), a synthetic somatostatin analogue, against sepsis-induced oxidative damage in the uterine and ovarian tissues of rats. Sepsis was induced by caecal ligation and puncture method in female Wistar albino rats. Sepsis and sham operated (control) groups received either saline or OCT (50μg/kg, i.p.; Novartis) immediately after the operation and at 12h. Twenty-four hours after the surgery, rats were decapitated and serum TNF-α levels and tissue malondialdehyde (MDA) content, glutathione (GSH) levels and myeloperoxidase (MPO) activity were determined in the uterus and ovaries. Oxidant-induced tissue fibrosis was determined by tissue collagen contents, while the extent of tissue injuries was analyzed microscopically. Sepsis increased serum TNF-α levels and resulted in decreased GSH levels and increased MDA levels, MPO activity and collagen contents in both the uterus and the ovaries (p &#60;0.05–0.001) indicating the presence of the oxidative damage, as also confirmed by histological analysis. On the other hand, OCT administration reversed these oxidant responses and reduced the severity of microscopic damage (p &#60;0.001). In conclusion, OCT protects against sepsis-induced oxidative injury of the uterine and ovarian tissues by diminishing neutrophil infiltration, an important source of oxygen free radicals. Our results suggest that OCT may be of therapeutic value in ameliorating sepsis-associated pelvic inflammation. [Copyright &y& Elsevier]

Abstract: Oxytocin (OT), a nonapeptide produced in the paraventricular and the supraoptical nuclei in the hypothalamus has a wide range of effects in the body. However, the role of OT on the gastrointestinal (GI) tract has to be settled. OT may participate in the regulation of motility, secretion, blood flow, cell turnover and release of neurotransmitters and/or peptides in the GI tract, possesses antisecretory and antiulcer effects, facilitates wound healing and is involved in the modulation of immune and inflammatory processes. The present work was conducted to assess the possible therapeutic effects of OT against the acetic acid-induced colonic injury in the rat. Methods: Colitis was induced by intracolonic administration of acetic acid (5%) in Sprague–Dawley rats (200–250g). Either saline or OT (0.5mg/kg) was injected subcutaneously, immediately after the induction of colitis and repeated two times a day for 4 days. On the 4th day, rats were decapitated and distal 8cm of the colon were removed for the macroscopic and microscopic damage scoring, determination of tissue wet weight index (WI), malondialdehyde (MDA) levels, an end product of lipid peroxidation; glutathione (GSH) levels, a key antioxidant; and myeloperoxidase (MPO) activity, as an indirect index of neutrophil infiltration. Colonic collagen content, as a fibrosis marker was also determined. Lactate deydrogenase (LDH) and tumor necrosis factor-alpha (TNF-α) levels were assayed in serum samples. In the acetic acid-induced colitis, macroscopic and microscopic damage scores, WI, MDA and MPO levels were significantly increased, while GSH levels were decreased when compared to control group (p &#60;0.05–&#60;0.001). Treatment with OT abolished the colitis-induced elevations in damage scores, WI, MDA and MPO levels and restored the GSH levels (p &#60;0.05–0.001). Similarly, acetic acid increased the collagen content of colonic tissues and OT-treatment reduced this value to the level of the control group. Serum LDH and TNF-α levels were also elevated in the acetic acid-induced colitis group as compared to control group, while this increase was significantly decreased by OT treatment. The results suggest that OT, which improves the antioxidative state of the colonic tissue and ameliorates oxidative colonic injury via a neutrophil-dependent mechanism, requires further investigation as a potential therapeutic agent in colonic inflammation. [Copyright &y& Elsevier]

Alendronate (ALD) causes serious gastrointestinal adverse effects. The aim of this study was to investigate whether taurine (TAU), a semi-essential amino acid and an antioxidant, improves the alendronate-induced gastric injury. Rats were administered 20 mg/kg ALD by gavage for 4 days, either alone or following treatment with TAU (50 mg/kg, i.p.). On the last day of treatment, following drug administration, pylorus ligation was performed and 2 h later, rats were killed and stomachs were removed. Gastric acidity and tissue ulcer index values, lipid peroxidation and glutathione (GSH) levels, myeloperoxidase (MPO) activity as well as the histologic appearance of the stomach tissues were determined. Chronic oral administration of ALD induced significant gastric damage, increasing lipid peroxidation, MPO activity and collagen content, as well as decreasing tissue GSH levels. Treatment with TAU prevented the damage and also the changes in biochemical parameters. Findings of the present study suggest that ALD induces oxidative gastric damage by a local irritant effect, and that TAU ameliorates this damage by its antioxidant and/or membrane-stabilizing effects. [ABSTRACT FROM AUTHOR]

Animal models of thermal injury implicate oxygen radicals as causative agents in local wound response and distant organ injury following burn. In this study we investigated the putative protective effects of 2-mercaptoethane sulfonate (MESNA) against oxidative kidney damage in rats with thermal injury. Under ether anaesthesia, shaved dorsum of the rats was exposed to 90 °C bath for 10 s to induce burn injury. Rats were decapitated either 6 or 24 h after burn injury. MESNA was administered i.p. immediately after burn injury. MESNA injections were repeated once more 12 h after the first injection in the 24 h burn group. In the control group the same protocol was applied except that the dorsum was dipped in a 25 °C water bath for 10 s. Kidney tissues were taken for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, protein oxidation (PO), myeloperoxidase (MPO) activity and collagen contents. Creatinine, urea concentrations (BUN) and lactate dehydrogenase (LDH) in blood were measured for the evaluation of renal functions and tissue damage, respectively. Tissues were also examined microscopically. Severe skin scald injury (30% of total body surface area) caused significant decrease in GSH level, significant increase in MDA level, protein oxidation (PO), MPO activity and collagen content of renal tissue. Serum creatinine was slightly increased at the early phase of thermal trauma but not changed in 24 h groups. On the other hand BUN and LDH were significantly elevated by thermal trauma in both 6 and 24 h of burn groups. Treatment of rats with MESNA significantly increased the GSH level and decreased the MDA level, PO, MPO activity, collagen contents, BUN and LDH. Since MESNA reversed the oxidant responses seen in burn injury, it seems likely that MESNA could protect against thermal trauma-induced renal damage. [Copyright &y& Elsevier]

The anti-tumour drug methotrexate (MTX) induces intestinal mucosa injury resulting in malabsorption and diarrhoea. The purpose of this study was to investigate whether exogenous melatonin could protect the gut from MTX-induced damage in rats. A single dose of MTX (20 mg kg−1, i.p.) was followed by i.p. saline or melatonin injections (10 mg kg−1, MTX + Mel) for the next 5 days. On the fifth day, intestinal transit was assessed using charcoal propagation. Rats were decapitated and small intestinal segments were fixed for light (LM) and scanning electron microscope (SEM) examinations. Other intestinal segments were stored to measure glutathione (GSH) and malondialdehyde (MDA) levels, myeloperoxidase (MPO) and ATPase activity. MTX led to loss of more than 10% of the initial body weight ( p < 0.01). Conversely, weight loss was markedly less in the melatonin-treated MTX group ( p < 0.05). Bowel motility was increased in MTX-treated rats, while the transit index in the MTX-Mel group was not different from the control group. MTX caused decreases in GSH levels and ATPase activity, with increases in MDA levels and MPO activity. These changes were reversed in MTX-Mel-treated rats ( p < 0.05- p < 0.001). LM and SEM in the MTX group revealed desquamation of surface epithelium and glandular degeneration, while the epithelium was slightly damaged in the MTX-Mel group. In conclusion, the present study demonstrates that melatonin is capable of reversing MTX-induced intestinal dysfunctions, indicating that it may be beneficial in ameliorating the symptoms of chemotherapy-induced enteritis. Copyright © 2004 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Sepsis is commonly associated with enhanced generation of reactive oxygen metabolites, which lead to multiple organ dysfunction. The aim of this study was to examine the role of melatonin, a potent antioxidant, in protecting the intestinal and bladder tissues against damage in a rat model of sepsis. Sepsis was induced by cecal ligation and perforation (CLP) in Wistar Albino rats. Sham operated (control) and CLP group received saline or melatonin (10 mg/kg, ip) 30 minutes prior to and 6 hours after the operation. Sixteen hours after the surgery, rats were decapitated and the intestinal and urinary bladder tissues were used for contractility studies, or stored for the measurement of malondialdehyde (MDA) content -an index of lipid peroxidation-, glutathione (GSH) levels -a key antioxidant- and myeloperoxidase (MPO) activity- an index of neutrophil infiltration-. Ileal and bladder MDA levels in the CLP group were significantly increased (p < 0.001) with concomitant decreases in GSH levels (p < 0.01–p < 0.001) when compared to the control group. Similarly, MPO activity was significantly increased (p < 0.001) in both ileum and bladder tissues. On the other hand, melatonin treatment significantly reversed (p < 0.001) the elevations in MDA and MPO levels, while reduced GSH levels were increased back to the control levels (p < 0.01–p < 0.001). In the CLP group, the contractility of the ileal and bladder tissues decreased significantly compared with controls. Melatonin treatment of the CLP group restored these responses. In this study, CLP induced dysfunction of the ileal and bladder tissue of rats was reversed by melatonin treatment. Moreover, melatonin, as an antioxidant, abolished the elevation in lipid peroxidation products and myeloperoxidase activity, and reduction in the endogenous antioxidant glutathione and thus protected the tissues against sepsis-induced oxidative damage. [Copyright &y& Elsevier]

Alendronate causes serious gastrointestinal adverse effects. The aim of this study was to investigate whether octreotide, a synthetic somatostatin analogue, improves the alendronate-induced gastric injury. Rats were administered 20 mg/kg alendronate by gavage for 4 days, either alone or following treatment with octreotide (0.1 ng/kg, i.p.). On the last day, following drug administration, pilor ligation was performed and 2 h later, rats were killed and stomachs were removed. Gastric acidity and tissue ulcer index values, lipid peroxidation (as assessed by malondialdehyde, MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity as well as the histologic appearance of the stomach tissues were determined. Chronic oral administration of alendronate induced significant gastric damage, increasing lipid peroxidation (37.1±3.2 nmol/g) and myeloperoxidase activity (57.6±3.7 U/g), while tissue glutathione levels (0.9±0.1 μmol/g) decreased. Treatment with octreotide prevented this damage as well as the changes in biochemical parameters (MDA: 23.4±1.3 nmol/g; MPO: 31.68 U/g; GSH: 1.5±0.1 μmol/g). Findings of the present study suggest that alendronate induces oxidative gastric damage by a local irritant effect, and that octreotide ameliorates this damage by inhibiting neutrophil infiltration and reducing lipid peroxidation. Therefore, its therapeutic role as a “ulcer healing” agent must be further elucidated in alendronate-induced gastric mucosal injury. [Copyright &y& Elsevier]

This study was designed to study the effects of the potential radioprotective properties of pharmacological doses of melatonin against organ damage induced by whole-body irradiation (IR) in rats. A total of 32 male Sprague-Dawley rats were exposed to irradiation performed with a LINAC producing 6 MV photons at a focus 100 cm distant from the skin. Under ketamine anaesthesia, each rat received a single whole-body dose of 800 cGy. Immediately before and after IR, rats were treated with either saline or melatonin (20 mg/kg and 10 mg/kg, ip) and decapitated at 12-h after exposure to irradiation. Another group of rats was followed for 72-h after IR, where melatonin (10 mg/kg, ip) injections were repeated once daily. Tissue levels of malondialdehyde (MDA)-an index of lipid peroxidation-, glutathione (GSH)—a key to antioxidant- and myeloperoxidase (MPO) activity-an index of neutrophil infiltration—were estimated in liver, lung, colon and intestinal tissues. The results demonstrate that both 12-h and 72-h following IR, tissue leves of MDA were elevated (p<0.05–0.001), while GSH levels were reduced (p<0.05–0.001) in all organs. On the other hand, melatonin, reduced the levels of MDA and increased the GSH levels significantly, (p<0.05–0.001). MPO activity was increased significantly in the colonic tissue at the both 12-h and 72-h, and in the hepatic tissue at the 72-h following IR, which were reduced by melatonin (p<0.01–0.001). In the lung tissue enzyme activity was decreased at 72nd h of post-irradiation. In conclusion, the increase in MDA levels and MPO activity and the concomitant decrease in GSH levels demonstrate the role of oxidative mechanisms in irradiation-induced tissue damage, and melatonin, by its free radical scavenging and antioxidant properties, ameliorates irradiation-induced organ injury. Thus, supplementing cancer patients with adjuvant therapy of melatonin may have some benefit for successful radiotherapy. [Copyright &y& Elsevier]

Mercury exerts a variety of toxic effects in the body. Lipid peroxidation, DNA damage and depletion of reduced glutathione by Hg(II) suggest an oxidative stress-like mechanism for Hg(II) toxicity. Melatonin, the main secretory product of the pineal gland, was recently found to be a potent free radical scavenger and antioxidant. N-Acetylcysteine, a precursor of reduced glutathione and an antioxidant, is used in the therapy of acute heavy metal poisoning. In this study the protective effects of melatonin in comparison to that of N-acetylcysteine against Hg-induced oxidative damage in the kidney, liver, lung and brain tissues were investigated. Wistar albino rats of either sex (200–250 g) were divided into six groups, each consisting of 8 animals. Rats were intraperitoneally injected with 1) 0.9% NaCl, control (C) group; 2) a single dose of 5 mg/kg mercuric chloride (HgCl2), Hg group; 3) melatonin in a dose of 10 mg/kg, 1 hr after HgCl2 injection, Hg-melatonin group; 4) melatonin in a dose of 10 mg/kg one day before and 1 hr after HgCl2 injection, melatonin-Hg-melatonin group; 5) N-acetylcysteine in a dose of 150 mg/kg, 1 hr after HgCl2 injection, Hg-N-acetylcysteine group, and 6) N-acetylcysteine in a dose of 150 mg/kg one day before and 1 hr after HgCl2 injection, N-acetylcysteine-Hg-N-acetylcysteine group. Animals were killed by decapitation 24 hr after the injection of HgCl2. Tissue samples were taken for determination of malondialdehyde, an end-product of lipid peroxidation; glutathione (GSH), a key antioxidant, and myeloperoxidase activity, an index of neutrophil infiltration. The results revealed that HgCl2 induced oxidative tissue damage, as evidenced by increases in malondialdehyde levels. Myeloperoxidase activity was also increased, and GSH levels were decreased in the liver, kidney and the lungs. All of these effects were reversed by melatonin or N-acetylcysteine treatment. Since melatonin or N-acetylcysteine administration reversed these responses, it seems likely that melatonin or N-acetylcysteine can protect all these tissues against HgCl2-induced oxidative damage. [ABSTRACT FROM AUTHOR]

Abstract: Acutely increased intra-abdominal pressure (IAP) can lead to multiple organ failure. As blood flow to intra-abdominal organs is reduced by high venous resistance, ischemia-reperfusion (I/R) injury plays an important role in the pathogenesis of abdominal compartment syndrome (ACS) following IAP. Melatonin, a secretory product of the pineal gland, is known to have free radical scavenging and antioxidative properties in several oxidative processes. The objective of this study was to examine the potential protective properties of melatonin on the oxidative organ damage in a rat model of ACS. Under ketamine anesthesia, an arterial catheter was inserted intraperioneally (i.p.) and using an aneroid manometer connected to the catheter, IAP was kept at 20 mmHg (ischemia group; I) for 1 hr. In the ischemia/reperfusion (I/R) group, pressure applied for an hour was decompressed and a 1-hr reperfusion period was allowed. In another IR group, melatonin was administered (10 mg/kg, i.p.) immediately before the decompression of IAP. The results demonstrate that tissue levels of malondialdehyde (MDA) and myeloperoxidase activity (MPO; index of tissue neutrophil infiltration) were elevated, while glutathione (GSH; a key to antioxidant) levels were reduced in both I and I/R groups (P < 0.05–0.001). Melatonin treatment in I/R rats reversed these changes (P < 0.01–0.001). Moreover, melatonin given to the I/R group reduced the elevations in serum aspartate aminotransferase, alanine aminotransferase and blood urea nitrogen levels and abolished the increase in serum creatinine levels. Our results indicate that melatonin, because of antioxidant and free radical scavenging properties, ameliorates reperfusion-induced oxidative organ damage. In conclusion, the results of the present study suggest that the therapeutic value of melatonin as a ‘reperfusion injury-limiting’ agent must be considered in ACS. [ABSTRACT FROM AUTHOR]

Abstract: Acetaminophen (AA) is a commonly used analgesic and antipyretic drug; however, when used in high doses, it causes fulminant hepatic necrosis and nephrotoxic effects in both humans and experimental animals. It has been reported that the toxic effects of AA are the result of oxidative reactions that take place during its metabolism. In this study we investigated if melatonin, vitamin E or N -acetylcystein (NAC) are protective against AA toxicity in mice. The doses of the antioxidants used were as follows: melatonin (10 mg/kg), vitamin E (30 mg/kg) and NAC (150 mg/kg). Blood urea nitrogen (BUN), serum creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels in blood, and glutathione (GSH), malondialdehyde (MDA), oxidized protein levels and myeloperoxidase (MPO) activity in liver and kidney tissues were measured. BUN and serum creatinine, ALT and AST levels which were increased significantly following AA treatment decreased significantly after pretreatment with either vitamin E, melatonin or NAC; however, they were not reduced to control levels. ALT and AST levels were significantly higher at 4 hr compared with the 24 hr levels after AA administration. However, BUN and creatinine levels were significantly elevated only at 24 hr. GSH levels were reduced while MDA, MPO and oxidized protein levels were increased significantly following AA administration. These changes were reversed by pretreatment with either melatonin, vitamin E or NAC. Liver toxicity was higher at 4 hr, whereas nephrotoxicity appeared to be more severe 24 hr after treatment with AA. Vitamin E was the least efficient agent in reversing AA toxicity while melatonin, considering it was given as at lower dose than either vitamin E or NAC, was the most effective. This may be the result of the higher efficacy of melatonin in scavenging various free radicals and also because of its ability in stimulating the antioxidant enzymes. [ABSTRACT FROM AUTHOR]

Oxygen free radicals have been implicated in mediating various pathological processes including burn-induced organ damage. This study was designed to determine the possible protective effect of aqueous garlic extract against oxidative organ damage distant from the original burn wound. Under ether anaesthesia, rats were subjected to severe skin scald injury covering 30% of total body surface area. Rats were decapitated either 2 h or 24 h after burn injury. Aqueous garlic extract (1 ml/kg) was administered i.p. immediately after burn injury. In the 24-h burn group injection was repeated once more (at 12 hour) following the burn injury. Liver, intestine and lung tissues were taken for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and protein oxidation (PO). Burn injury caused a significant decrease in GSH level, and significant increases in MDA and PO levels, and MPO activity at post-burn 2 and 24 hours. Since garlic extract reversed these oxidant responses it seems likely that garlic extract protects tissues against oxidative damage. [Copyright &y& Elsevier]

The local thermal trauma activates a number of systemic mediator cascades, e.g. a complement activation, cytokine production, resulting in a generalized sequestration and a priming of local and systemic neutrophils and macrophages. We aimed to determine the possible protective effect of octreotide (OCT), a synthetic somatostatin analogue, against burn-induced intestinal tissue damage possibly by inhibiting neutrophil infiltration.Under brief ether anaesthesia, shaved dorsum of the rats was exposed to 90 °C bath for 10 s to induce burn injury. Rats were decapitated either 3, 24 or 72 h after burn injury. Octreotide (10 μg/kg) or saline was administered subcutaneously (s.c.) immediately after the burn injury. In the 24- and 72-h burn groups, OCT injections were repeated three times daily. In the sham group the same protocol was applied except that the dorsum was dipped in a 25 °C water bath for 10 s Malondialdehyde (MDA) and glutathione (GSH) levels and myeloperoxidase (MPO) activity were determined in the intestinal tissue. The results demonstrate that burn injury results in significant neutrophil accumulation, as evidenced by increases in MPO activity. The increase in MDA and the concomitant decrease in GSH levels demonstrate the role of oxidative mechanisms in burn injury. OCT may have some beneficial therapeutic effects by reducing neutrophil-dependent injury and related lipid peroxidation following burn trauma. [Copyright &y& Elsevier]

Animal models of burn injury indicate oxygen radicals as causative agents in the local wound response, as well as in the development of burn shock and distant organ injury. This study was designed to determine the possible protective effect of melatonin treatment against oxidative damage in the liver, lung and intestine induced by burn injury. Under ether anaesthesia, the shaved dorsum of rats was exposed to a 90 °C bath for 10 s to induce burn injury. Rats were decapitated either 3 or 24 h after burn injury. Melatonin was administered i.p. immediately after burn injury. In the 24 h burn group, melatonin injections were repeated for two more occasions. In the sham group the same protocol was applied except that the dorsum was dipped in a 25 °C water bath for 10 s. Liver, lung and intestine tissues were taken for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and protein oxidation (PO). Severe skin scald injury (30% of total body surface area) caused a significant decrease in GSH level, significant increases in MDA and PO levels, and MPO activity at postburn 3 and 24 h. Treatment of rats with melatonin (10 mg/kg) significantly elevated the reduced GSH levels while it decreased MDA and PO levels as well as MPO activity. [Copyright &y& Elsevier]

Animal models of thermal trauma implicate oxygen radicals as causative agents in local wound response and distant organ injury following burn . This study was designed to determine the effect of melatonin treatment on levels of glutathione (GSH), malondialdehyde (MDA), protein oxidation (PO) and myeloperoxidase (MPO) activity in the kidney tissues of rats with thermal injury. Under ether anaesthesia, shaved dorsum of the rats was exposed to 90 °C bath for 10 s to induce burn injury. Rats were decapitated either 3 h or 24 h after burn injury. Melatonin was administered i.p. immediately after burn injury. In the 24-h burn group melatonin injections were repeated for two more occasions. In the sham group the same protocol was applied except that the dorsum was dipped in a 25 °C water bath for 10 s. Severe skin scald injury (30% of total body surface area) caused a significant decrease in GSH level, and significant increases in MDA and PO levels, and MPO activity at post-burn 3 and 24 hours. Treatment of rats with melatonin (10 mg/kg) significantly elevated the reduced GSH levels while it decreased MDA and PO levels as well as MPO activity. [Copyright &y& Elsevier]

AbstractIntroductionMethodsResultsConclusionPostmenopausal diabetes is a condition that affects millions of women and their quality of life. Also, kidney and small intestine tissues are damaged due to diabetes. The present study aimed to examine the protective effects of an extract prepared from Myrtus communis leaves on kidney and small intestine tissues against experimentally created postmenopausal diabetes.For this purpose, experimental rats were randomly divided into six groups (Control; ovariectomy:OVX, diabetic:D, ovariectomy + diabetic:OVX + D, ovariectomy + diabetic + oestrogen:OVX + D+E2, ovariectomy + diabetic + MC: OVX + D+MC) and kidney and small intestine tissues were taken after the experimental procedure.Evaluations of biochemical parameters (glutathione and glutathione-related enzymes, antioxidant enzymes, etc.) showed that MC had a protective effect on kidney and small intestine tissues in diabetes and ovariectomy groups.It can be suggested that MC extract has a protective effect on small intestine and kidney tissues in postmenopausal diabetes and may be a good herbal source for this purpose. [ABSTRACT FROM AUTHOR]