Search

Copyright of Marmara Pharmaceutical Journal is the property of Marmara University, Faculty of Pharmacy and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Marmara Pharmaceutical Journal is the property of Marmara University, Faculty of Pharmacy and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Traumatic injury to the central nervous system results in the delayed dysfunction and neuronal death. Impaired mitochondrial function, generation of reactive oxygen species (ROS), and lipid peroxidation occur soon after traumatic spinal cord injury (SCI), while the activation of compensatory molecules that neutralize ROS occurs at later time points. The aim of the current study was to investigate the putative neuroprotective effect of the COX2 inhibitor meloxicam in a rat model of SCI. In order to induce SCI, a standard weight-drop method that induced a moderately severe injury (100 g/cm force) at T10, was used. Injured animals were given either 2 mg/kg meloxicam or saline 30 min postinjury by intraperitoneal injection. At seven days postinjury, neurological examination was performed and rats were decapitated. Spinal cord samples were taken for histological examination or determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and DNA fragmentation. Formation of ROS in spinal cord tissue samples was monitored by using a chemiluminescence (CL) technique. SCI caused a significant decrease in spinal cord GSH content, which was accompanied with significant increases in CL, MDA levels, MPO activity, and DNA damage. On the other hand, meloxicam treatment reversed all these biochemical parameters as well as SCI-induced histopathological alterations. Furthermore, impairment of the neurological functions due to SCI was improved by meloxicam treatment. The present study suggests that meloxicam, reduces SCI-induced oxidative stress and exerts neuroprotection by inhibiting lipid peroxidation, GSH depletion, and DNA fragmentation. [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 present study was undertaken to determine whether resveratrol (RVT) could ameliorate ionizing radiation-induced oxidative injury. After a 10-days pre-treatment with RVT (10 mg/kg/day p.o.), rats were exposed to whole-body IR (800 cGy) and the RVT treatment was continued for 10 more days after the irradiation. Irradiation caused a significant decrease in glutathione level, while malondialdehyde levels, myeloperoxidase activity and collagen content were increased in the liver and ileum tissues. Similarly, plasma lactate dehydrogenase and pro-inflammatory cytokine levels, 8-hydroxy-2'-deoxyguanosine and leukocyte apoptosis were elevated, while antioxidant-capacity was reduced in the irradiated rats as compared with the control group. Furthermore, Na+, K+-ATPase activity was inhibited and DNA fragmentation was increased in the ileal tissues. Resveratrol treatment reversed all these biochemical indices, as well as histopathological alterations induced by irradiation. In conclusion, supplementing cancer patients with adjuvant therapy of resveratrol may have some benefit for a more successful radiotherapy. [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]

Oxidative stress has detrimental effects in several models of neurodegenerative diseases, including subarachnoid hemorrhage (SAH). This study investigated the putative neuroprotective effect of melatonin, a powerful antioxidant, in a rat model of SAH. Male Wistar albino rats were divided as control, vehicle-treated SAH, and melatonin-treated (10 mg/kg, i.p.) SAH groups. To induce SAH, 0.3 mL blood was injected into cisterna magna of rats. Forty-eight hours after SAH induction, neurological examination scores were measured and the rats were decapitated. Brain tissue samples were taken for blood–brain barrier (BBB) permeability, brain water content, histological examination, or determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO), and Na+-K+-ATPase activities. Formation of reactive oxygen species in brain tissue samples was monitored by using a chemiluminescence (CL) technique. The neurological examination scores were increased in SAH groups on the second day of SAH induction and SAH caused a significant decrease in brain GSH content and Na+-K+-ATPase activity, which was accompanied with significant increases in CL, MDA levels, and MPO activity. On the other hand, melatonin treatment reversed all these biochemical indices as well as SAH-induced histopathological alterations, while increased brain water content and impaired BBB were also reversed by melatonin treatment. This study suggests that melatonin, which can easily cross BBB, alleviates SAH-induced oxidative stress and exerts neuroprotection by preserving BBB permeability and by reducing brain edema. [ABSTRACT FROM AUTHOR]

Abstract: Objective: This investigation confirms the role of free radicals in naphthalene-induced toxicity and elucidates the mechanism of resveratrol (RVT). Methods: Both male and female BALB-c mice were administered with naphthalene (100mg/kg, i.p.) for 30 days, either along with saline or along with RVT (10mg/kg, orally). At the end of the experiment, following treatment and sacrifice of animals by decapitation, lung, liver and kidney tissue samples were taken for histological examination or determination of malondialdehyde (MDA), glutathione (GSH), myeloperoxidase (MPO) activity and collagen contents. 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-β, IL-6 and total antioxidant capacity (AOC) were assayed in plasma samples. Results: Naphthalene administration caused a significant decrease in tissue GSH and plasma AOC, which was accompanied with significant increases in tissue MDA and collagen levels and MPO activity. Moreover, the pro-inflammatory mediators (TNF-α, IL-β, IL-6), LDH activity, AST, ALT, creatinine and BUN levels were significantly increased in the naphthalene group. On the other hand, RVT treatment reversed all these biochemical indices as well as histopathological alterations induced by naphthalene. Conclusions: Oxidative mechanisms play an important role in naphthalene-induced tissue damage, and RVT, by inhibiting neutrophil infiltration, balancing oxidant–antioxidant status, and regulating the generation of inflammatory mediators, ameliorates oxidative organ injury due to naphthalene toxicity. [Copyright &y& Elsevier]

Endosulfan is a chlorinated cyclodiene insecticide which induces oxidative stress. In this study, we investigated the possible protective effect of melatonin, an antioxidant agent, against endosulfan (Endo)-induced toxicity in rats. Wistar albino rats (n = 8) were administered endosulfan (22 mg/kg/day orally) followed by either saline (Endo group) or melatonin (10 mg/kg/day, Endo + Mel group) for 5 days. In other rats, saline (control group) or melatonin (10 mg/kg/day, Mel group) was injected for 5 days, following corn oil administration (vehicle of endosulfan). Measurement of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen content were performed in liver and kidney. Furthermore, aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and creatinine levels, lactate dehydrogenase (LDH) activity were measured in the serum samples, while tumor necrosis factor-α (TNF-α), interleukin-β (IL-β) and total antioxidant capacity (AOC) were assayed in plasma samples. Endosulfan administration caused a significant decrease in tissue GSH and plasma AOC, which was accompanied with significant rises in tissue MDA and collagen levels and MPO activity. Moreover, the proinflammatory mediators (TNF-α and IL-β), LDH activity, AST, ALT, creatinine and BUN levels were significantly elevated in the endosulfan-treated rats. On the other hand, melatonin treatment reversed all these biochemical alterations induced by endosulfan. Our results suggest that oxidative mechanisms play an important role in endosulfan-induced tissue damage and melatonin, by inhibiting neutrophil infiltration, balancing oxidant–antioxidant status and regulating the generation of inflammatory mediators, ameliorates oxidative organ injury as a result of endosulfan toxicity. [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]

Background/Aims: This investigation elucidates the role of free radicals in ethanol-induced gastric mucosal erosion and the protective effect of lipoic acid. Methods: After overnight fasting, Wistar albino rats were orally treated with 1 ml of absolute ethanol to induce gastric erosion. Lipoic acid (100 mg/kg) was given orally for 3 days before ethanol administration. Mucosal damage was evaluated 1 h after ethanol administration by macroscopic examination and histological analysis. Additional tissue samples were taken for measurement of malondialdehyde, glutathione (GSH), and myeloperoxidase activity. Production of reactive oxidants and oxidant-induced DNA fragmentation and Na+,K+-ATPase activity were also assayed in the tissue samples. Results: Generation of reactive oxygen species and lipid peroxidation associated with neutrophil infiltration play an important role in the pathogenesis of gastric mucosal damage induced by ethanol. Furthermore, oxidants depleted tissue GSH stores and impaired membrane structure as Na+,K+-ATPase activity was inhibited. On the other hand, lipoic acid treatment reversed all these biochemical indices as well as the histopathological changes induced by ethanol. Conclusion: These data suggest that lipoic acid administration effectively counteracts the deleterious effect of ethanol-induced gastric mucosal injury and attenuates gastric damage through its antioxidant effects. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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]

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]

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]

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]

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]

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: 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]

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]

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]

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]

Regarding the mechanisms of methotrexate (MTX) hepatotoxicity and nephrotoxicity, several hypotheses have been put forward, among which oxidative stress (including depletion of glutathione) is likely. This investigation elucidates the role of free radicals in MTX-induced toxicity and the protection by melatonin. Wistar albino rats were injected with MTX intraperitoneally. Following a single dose of MTX (20 mg/kg), either saline (MTX group) or melatonin (10 mg/kg, MTX + Mel group) was administered for 5 days. In other rats, physiologic saline (control group) or melatonin (10 mg/kg, Mel group) was injected for 5 days, following a single injection of saline. On the sixth day, rats were killed to obtain blood, liver, and kidney tissue samples. Malondialdehyde (MDA), an end product of lipid peroxidation, and glutathione (GSH), a key antioxidant, levels were evaluated in blood and tissue homogenates. Reactive oxygen metabolite-induced inflammatory changes in kidney and liver tissues were evaluated by measuring myeloperoxidase (MPO) activity, an index of neutrophil infiltration. MTX administration resulted in increased MDA levels and MPO activity and decreased GSH levels in the blood, liver, and kidney whereas melatonin reversed these effects. When melatonin was administered alone, no significant changes in biochemical parameters were noted. In conclusion, the present study suggests that melatonin may be of therapeutic benefit when used with MTX. [ABSTRACT FROM AUTHOR]

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 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]

Abstract: Mechanisms of burn-induced skin and remote organ injury involve oxidant generation and the release of pro-inflammatory cytokines. In this study the possible antioxidant and anti-inflammatory effects of ghrelin were evaluated in a rat model of thermal trauma. Wistar albino rats were exposed to 90°C bath for 10s to induce thermal trauma. Ghrelin, was administered subcutaneously (10ng/kg/day) after the burn injury and repeated twice daily. Rats were decapitated at 6h and 48h after burn injury and blood was collected for the analysis of pro-inflammatory cytokines (TNF-α and IL-1β), lactate dehydrogenase (LDH) activity and antioxidant capacity (AOC). In skin, lung and stomach tissue samples malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) and Na+–K+-ATPase activity were measured in addition to the histological analysis. DNA fragmentation ratio in the gastric mucosa was also evaluated. Burn injury caused significant increase in both cytokine levels, and LDH activity, while plasma AOC was found to be depleted after thermal trauma. On the other hand, in tissue samples the raised MDA levels, MPO activity and reduced GSH levels, Na+–K+-ATPase activity due to burn injury were found at control levels in ghrelin-treated groups, while DNA fragmentation in the gastric tissue was also reduced. According to the findings of the present study, ghrelin possesses a neutrophil-dependent anti-inflammatory effect that prevents burn-induced damage in skin and remote organs and protects against oxidative organ damage. [Copyright &y& Elsevier]

Abstract: Background: Urinary tract infection (UTI) may cause inflammation of the renal parenchyma and may lead to impairment in renal function and scar formation. Oxidant injury and reactive oxygen species (ROS) have been found responsible in the pathogenesis of UTI. The neurohypophyseal hormone oxytocin (OT) facilitates wound healing and is involved in the modulation of immune and inflammatory processes. We investigated the possible therapeutic effects of OT against Eschericia coli induced pyelonephritis in rats both in the acute and chronic setting. Methods: Twenty-four Wistar rats were injected 0.1ml solution containing E. coli ATCC 25922 1010 colony forming units/ml into left renal medullae. Six rats were designed as sham group and were given 0.1ml 0.9% NaCl. Pyelonephritic rats were treated with either saline or OT immediately after surgery and at daily intervals. Half of the pyelonephritic rats were decapitated at the 24th hour of E. coli infection, and the rest were followed for 7 days. Renal function tests (urea, creatinine), systemic inflammation markers [lactate dehydrogenase (LDH) and tumor necrosis factor alpha (TNF-α)] and renal tissue malondialdehyde (MDA) as an end product of lipid peroxidation, glutathione (GSH) as an antioxidant parameter and myeloperoxidase (MPO) as an indirect index of neutrophil infiltration were studied. Results: Blood urea, creatinine, and TNF-α levels were increased, renal tissue MDA and MPO levels were elevated and GSH levels were decreased in both of the pyelonephritic (acute and chronic) rats. All of these parameters and elevation of LDH at the late phase were all reversed to normal levels by OT treatment. Conclusion: OT alleviates oxidant renal injury in pyelonephritic rats by its anti-oxidant actions and by preventing free radical damaging cascades that involves excessive infiltration of neutrophils. [Copyright &y& Elsevier]

Abstract: The potential protective effect of OT on a stress-aggravated colitis model in rats and the involvement of OT receptors were evaluated. Holeboard test performances of Sprague–Dawley rats were videotaped for 5min to evaluate their exploratory behavior as indices of anxiety levels. A subgroup of rats was exposed to a 30-min psychological stress procedure, “water avoidance stress”, for 5 consecutive days. Colitis was induced by intracolonic administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS, 30mg/ml), while the sham group was administered with intracolonic saline. Either OT (0.5mg/kg/day; subcutaneously) or OT + OT receptor antagonist atosiban, was given (1mg/kg/day; intraperitoneally) for 3 consecutive days after colitis induction. On the third day, holeboard tests were performed again and the rats were decapitated. Macroscopic lesions were scored and the degree of oxidant damage was evaluated by colonic myeloperoxidase activity (MPO), malondialdehyde (MDA) and glutathione (GSH) levels, and by histological analysis. Colitis induction inhibited exploratory behavior, indicating increased anxiety level, while exposure to stress further exaggerated the degree of anxiety. Macroscopic scores as well as MDA and MPO levels revealed that tissue damage is aggravated in the stressed group with colitis while antioxidant GSH levels were decreased in both colitis and stressed colitis groups. Oxytocin treatment decreased the exacerbated anxiety, MPO and MDA levels and inflammatory cell infiltration and submucosal edema while atosiban abolished all the protective effects of OT. Thus, the results showed that the anxiolytic and antioxidant effects of OT are mediated via its receptors, since atosiban reversed the protective impact of OT on colonic injury while blocking its stress-relieving effect. [Copyright &y& Elsevier]

Abstract: Regarding the mechanisms of ifosfamide (IFO)-induced urinary toxicity, several hypotheses have been put forward, among which oxidative stress and depletion of glutathione are suggested. This investigation elucidates the role of free radicals in IFO-induced toxicity and the protection by resveratrol, a natural phytoalexin. Wistar albino rats were injected intraperioneally with saline (0.9% NaCl; control), saline+resveratrol (RVT; 10 mg/kg/day), ifosfamide (IFO; 50 mg/kg/day) or IFO+RVT for 5 days. Urine was collected for 24 h during the 5th day, and at the 120th h after the first injections, animals were killed by decapitation and trunk blood was collected. Lactate dehydrogenase (LDH) activity, total antioxidant capacity (AOC) and pro-inflammatory cytokines TNF-α, IL-β and IL-6 were assayed in plasma samples. Kidney and bladder tissues were obtained for biochemical and histological analysis. Formation of reactive oxygen species in the tissue samples was monitored by using chemiluminescence (CL) technique with luminol and lucigenin probes. The results demonstrated that IFO induced a Fanconi syndrome characterized by increased urinary sodium, phosphate, glucose and protein, along with increased serum creatinine and urea levels. On the other hand, RVT markedly ameliorated the severity of renal dysfunction induced by IFO. Furthermore IFO caused a significant decrease in plasma AOC, which was accompanied with significant increases in the levels of the pro-inflammatory mediators and LDH activity, while RVT treatment reversed all these biochemical indices. In the saline-treated IFO group, glutathione levels were decreased significantly, while the malondialdehyde levels, myeloperoxidase activity and collagen content were increased in both tissues, which were in parallel with the increases in CL values. In the RVT-treated IFO group, all of these oxidant responses were prevented significantly. Our results suggest that IFO causes oxidative damage in the renal and bladder tissues and resveratrol, via its antioxidant effects, protects these tissues. Therefore, its therapeutic role in preventing the development of chemotherapeutic drug-induced major toxicity in the urinary system requires further elucidation. [Copyright &y& Elsevier]

Abstract: The protective effect of β-glucan against oxidative injury caused by acetaminophen was studied in mice liver. BALB-c mice (25–30 g) were pre-treated with β-d-glucan (50 mg/kg, p.o.) for 10 days and on the 11th day they received an overdose of acetaminophen (900 mg/kg, i.p.). Four hours after the acetaminophen injection, mice were decapitated and their blood was taken to determine serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and tumor necrosis factor-alpha (TNF-α) levels. Tissue samples of the liver were taken for histological examination or for the determination of levels of malondialdehyde, an end product of lipid peroxidation; glutathione (GSH), a key antioxidant; and myeloperoxidase activity, an index of tissue neutrophil infiltration. The formation of reactive oxygen species in hepatic tissue samples was monitored by using the chemiluminescence technique with luminol and lucigenin probes. Acetaminophen caused a significant decrease in the GSH level of the tissue, which was accompanied with significant increases in the hepatic luminol and lucigenin chemiluminescence values, malondialdehyde level, MPO activity and collagen content. Similarly, serum ALT, AST levels, as well as LDH and TNF-α, were elevated in the acetaminophen-treated group when compared with the control group. On the other hand, β-d-glucan treatment reversed all these biochemical indices, as well as histopathological alterations that were induced by acetaminophen. In conclusion, these results suggest that β-d-glucan exerts cytoprotective effects against oxidative injury through its antioxidant properties and may be of therapeutic use in preventing acetaminophen toxicity. [Copyright &y& Elsevier]

Reoxygenation of the ischemic tissue promotes the generation of various reactive oxygen metabolites (ROM) which are known to have deleterious effects on various cellular functions.This study was designed to determine the possible protective effect of mesna (2-Mercaptoethane Sulfonate) on renal ischemia/reperfusion (I/R) injury. Wistar albino rats were unilaterally nephrectomized, and 15 days later they were subjected to 45 min of renal pedicle occlusion followed by 6 h of reperfusion. Mesna (MESNA, 150 mg/kg, i.p.; an effective dose against I/R injury) or vehicle was administered twice, 15 min prior to ischemia and immediately before the reperfusion period. At the end of the reperfusion period, rats were killed by decapitation. Kidney samples were taken for histological examination or determination of the free radicals, renal malondialdehyde (MDA) and glutathione (GSH) levels, and myeloperoxidase (MPO) activity. Renal tissue collagen content, as a fibrosis marker was also determined. Creatinine and urea concentrations in blood were measured for the evaluation of renal function. The results demonstrated that renal I/R caused nephrotoxicity, as evidenced by increases in blood urea and creatinine levels, which was reversed by MESNA treatment. Increased free radical levels, as assessed by nitroblue-tetrazolium test were reduced with MESNA. Moreover, the decrease in GSH and increases in MDA levels, and MPO activity induced by I/R indicated that renal injury involves free radical formation. Treatment of rats with MESNA restored the reduced GSH levels while it decreased MDA levels as well as MPO activity. Increased collagen contents of the kidney tissues by I/R were reversed back to the control levels by MESNA treatment. Since MESNA administration reversed these oxidant responses, improved renal function and microscopic damage, it seems likely that MESNA protects kidney tissue against I/R induced oxidative damage. [Copyright &y& Elsevier]

Acutely increased intra-abdominal pressure (IAP) may lead to abdominal compartment syndrome (ACS), which ischaemia/reperfusion (I/R) injury plays an important role. The main goal of the management of ACS is to lower the intra-abdominal pressure despite reperfusion injury. Octreotide (OCT), a synthetic somatostatin analogue, lowers the splanchnic perfusion. The aim of this study was to investigate whether OCT improves the reperfusion injury after decompression of acute abdominal hypertension.Under anesthesia, a catheter was inserted intraperitoneally and using an aneroid manometer connected to the catheter, IAP was kept at 20 mmHg (ischemia group; I) for 1 h. In the I/R group, pressure applied for an hour was decompressed and 1 h reperfusion period was allowed. In another group of I/R, OCT was administered (50 μg/kg i.p.) immediately before the decompression of IAP. The results demonstrate that kidney and lung tissues of malondialdehyde (MDA; an end product of lipid peroxidation) levels and myeloperoxidase (MPO; index of tissue neutrophil infiltration) activity were elevated, while glutathione (GSH; a key to antioxidant) levels were reduced in I/R group (P<0.001). Moreover, OCT treatment applied in the I/R group reduced the elevations in blood urea nitrogen (BUN) and serum creatinine levels. Our results implicate that IAP causes oxidative organ damage and OCT, by reducing splanchnic perfusion and controlling the reperfusion of abdominal organs, could improve the reperfusion-induced oxidative damage. Therefore, its therapeutic role as a “reperfusion injury-limiting” agent must be further elucidated in IAP-induced abdominal organ injury. [Copyright &y& Elsevier]