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Objective: Nephrolithiasis is a common urological disease that can lead to renal failure. Oxidative stress has been shown to be a contributing factor for nephrolithiasis and many agents have been studied to prevent and treat oxidative stress-related nephrolithiasis and renal damage. Myrtus communis (MC) extract has been shown to be an important antioxidant in different animal models. In this study, MC extract was administered preventively or therapeutically to rats with kidney stones, and its effectiveness was investigated., Methods: Wistar albino rats were divided into four groups (n=8); control (C), ethylene glycol (EG), EG+preventive MC, and EG+curative MC groups. The nephrolithiasis model was created by adding 0.75% EG to drinking water for 8 weeks. Ultimately, 24-hour urine was collected to measure calcium, citrate, and creatinine levels. After decapitation, kidney tissues were harvested for histological analyses, measurement of osteopontin and 8-hydroxydeoxyguanosine (8-OHdG) levels, and N-acetyl-β-glucosaminidase (NAG), myeloperoxidase (MPO) and caspase-3 activities., Results: In 24-hour urine samples, calcium, citrate and creatinine levels were decreased in the EG group, while oxalate levels were increased and in treatment groups these parameters returned to control levels. MPO, 8-OHdG, caspase-3 and NAG activity were significantly increased in tissue and these changes were reversed in both MC groups. Histological findings also supported the biochemical parameters., Conclusion: MC can reduce oxidative stress and histopathological changes in kidney tissues in rat nephrolithiasis model when used as either a preventive or therapeutic agent. If supported with further clinical trials, MC might have clinical implications in preventing oxidative renal cell injury and ultimately kidney stone formation., Competing Interests: No conflict of interest was declared by the authors., (© Copyright 2024 by Istanbul Provincial Directorate of Health.)

Objectives: The aim of the study is to examine the effect of Ambroxol on TNF-α and IL-1β released after liver ischemia-reperfusion injury., Background: Many drugs are being tried to reduce ischemia-reperfusion injury, which is life threating problem after many liver surgeries. In this study, it was investigated whether Ambroxol reduces the release of pro-inflammatory cytokines released after liver ischemia-reperfusion injury., Methods: Twenty-four Wistar albino rats were divided into 3 groups as Control (CTR; n=8), hepatic ischemia reperfusion (H-IR; n=8) and hepatic ischemia reperfusion+Ambroxol (H-IR+AMB; n=8). In H-IR+AMB group, Ambroxol (30 mg/kg) was administered orally 30 minutes before ischemia period. In H-IR and H-IR+AMB groups underwent 45 minutes of hepatic ischemia followed by a 60-minute reperfusion period. After reperfusion period, tissue and blood samples were collected from euthanised animals. ALT, AST, ALP, LDH, TNF-α, IL-1β concentrations and liver tissues were evaluated., Results: Serum ALT, ALP, AST, LDH, TNF-α and IL-1β values were lower in the H-IR+AMB group compared to the H-IR group. In the histopathological examination, hepatocyte degeneration and congestion in the H-IR group were higher than in the H-IR+AMB group., Conclusion: It was determined that Ambroxol treatment suppressed the production of pro-inflammatory cytokines TNF-α and IL-1β in rats undergoing hepatic ischemia reperfusion (Tab. 1, Fig. 2, Ref. 28).

A review of the literature indicated that sirtuin-1 expression, a regulator of nitric oxide bioavailability in erectile dysfunction (ED) after melatonin therapy, has not yet been investigated. The objective of this study was to evaluate the protective effects of melatonin for erectile function with sirtuin-1 protein expression in type 1 diabetic rat models. Fifty male Sprague Dawley rats were placed into five groups. Except for those in the control group (C), each animal received a single dose (60 mg/kg) of streptozotocin to induce diabetes. The animals were placed into the diabetes (D) group, insulin (I) group (6 U/kg/day), melatonin (Mel) group (10 mg kg -1  day -1 ) and combined treatment (I + Mel) group. Ten weeks later, the serum testosterone levels, intracavernosal pressure (ICP), mean arterial pressure (MAP), malondialdehyde (MDA), cyclic guanosine monophosphate (c-GMP), 8-hydroxydeoxyguanosine (8-OHdG), nitric oxide synthase (NOS), caspase-3 activity, sirtuin-1 and endothelial nitric oxide synthase (eNOS) protein expression and histological findings were assessed. The mean ICP/MAP ratio for the D group was lower than the mean ratios for the other groups. The treatment groups, particularly the I + Mel group, exhibited lower 8-OHdG and MDA levels and caspase-3 activity than the D group. The sirtuin-1 and eNOS expression and cavernosal tissue (CT) histology seemed to have been preserved by the melatonin and/or insulin therapy. These results were indicative of a profound protective effect of melatonin by the activation of sirtuin-1 protein expression against hyperglycemia-induced oxidative CT injury., (© 2020 Blackwell Verlag GmbH.)

Objective: The present study aims to investigate the therapeutic effects of resveratrol (RES) on isoproterenol (ISO) induced myocardial injury rat model., Methods: Catecholamine-induced heart damage was induced by ISO treatment for 30 days. The rats were divided into four groups as follows: the control group received saline, the ISO group received 5.0 mg/kg ISO, the RES group received 10 mg/kg RES, and the ISO-RES group received 10 mg/kg RES and 5 mg/kg ISO treatments for 30 days. Following echocardiographic measurements and body weight recorded, the rats were decapitated. Plasma and cardiac tissue samples obtained by decapitation were analyzed using biochemical, histopathological, molecular and immunohistochemical methods., Results: In the ISO group, Na + /K + ATPase activity and ATP content, GSH, and caveolin-3 levels were low. LDH, CK and lysosomal enzyme activities, MDA level, and MPO activity were found to be high. It was determined that GSH and MDA levels and MPO, Na + /K + ATPase activity, ATP content caveolin-3 levels changes that arose from ISO treatment were suppressed by RES treatment., Conclusion: RES treatment has ameliorated all the functional and biochemical parameters. The results obtained in this study suggest that RES is a promising supplement against catecholamine exposure as it improves antioxidant defense mechanisms in the heart. In the light of above-mentioned data, RES can be assumed as a promising agent in ameliorating the oxidative injury of the myocardium., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (Copyright: © 2020 by Istanbul Northern Anatolian Association of Public Hospitals.)

Background/objective: The present study investigated the potent therapeutic effects of Ruscogenin, main steroid sapogenin of traditional Chinese plant called 'Ophiopogon japonicas', on chronic ulcer model established with acetic acid in rats., Methods: 24 rats were attenuated to the sham (2 ml/kg/day isotonic solution), control (untreated ulcer) and treatment (3 ml/kg/day ruscogenin) groups. After treatment for 2 weeks, gastric tissues were collected and prepared for light microscopic (H&E), immunohistochemical (Collagen I, III and IV) and biochemical analysis [Epidermal growth factor (EGF), Prostaglandin E2 (PGE2), Tumor Necrosis Factor alpha (TNF-α), Interleukin 6 and 8 (IL-6 and IL-8), Lipid Peroxidase (LPO), Myeloperoxidase (MPO), Glutathione (GSH) and Glutathione Peroxidase (GSH-Px)] and transmission electron microscopy (TEM)., Results: Macroscopic scoring showed that the ulceration area of ruscogenin-treated group decreased compared with control group. Immunohistochemical analysis revealed ruscogenin ameliorated and restored the levels of Collagen I and IV to the levels of sham group. Tissue levels of EGF and PGE2 enhanced significantly in untreated ulcer group while were higher in treated ulcer group than the control group. TNF-α, IL-6, IL-8, LPO, MPO levels increased significantly in control group whereas decreased in treated rats after ruscogenin treatment. However, levels of GSH and GSH-Px increased significantly in treatment group. TEM showed chief cells and parietal cells of ulcer group having degenerated organelles while ruscogenin group had normal ultrastructure of cells., Conclusion: There are potent anti-inflammatory and anti-oxidant effects of ruscogenin on gastric ulcer and may be successfully used as a safe and therapeutic agent in treatment of peptic ulcer., (Copyright © 2019. Published by Elsevier Taiwan LLC.)

Purpose: To determine the potential protective and therapeutic effects and action mechanism of ruscogenin on cerulein-induced acute pancreatitis (AP) model in rats., Methods: Overall, 32 rats were attenuated to the sham (2-mL/kg/day isotonic solution for 4 weeks), control (20-µg/kg cerulein-induced AP for 12 hours), prophylaxis groups (cerulein-induced AP following 3-mL/kg/day ruscogenin for 4 weeks) and treatment (3-mL/kg/day ruscogenin following cerulein-induced AP for 12 hours). Blood samples were collected for biochemical analysis of nitric oxide synthase 1 (NOS1/neuronal NOS), malondialdehyde (MDA) and intercellular adhesion molecule 1 (ICAM-1). After sacrification, pancreas tissues were collected and prepared for light microscopic (hematoxylin and eosin), immunohistochemical (nuclear factor kappa B) and biochemical analysis (tumor necrosis factor-alpha [TNF-α], interleukin-6 and 1β [IL-6 and IL-1β], CRP, high-sensitivity CRP [hs-CRP] amylase, lipase, and ICAM-1). Ultrastructural analysis was performed by transmission electron microscopy., Results: The protective and therapeutic actions of ruscogenin were accomplished by improvements in histopathology, by decreasing blood cytokine levels of CRP, hs-CRP levels, TNF-α, IL-6, IL-1β, ICAM-1, by reducing the pancreatic enzymes amylase and lipase in blood, and by suppressing the expression of nuclear factor kappa B, ICAM-1, and NOS-1, but not MDA in pancreatic tissues. Ruscogenin also improved cerulein-induced ultrastructural degenerations in endocrine and exocrine cells, especially in treatment group., Conclusion: The present findings have demonstrated the beneficial protective and therapeutical effects of ruscogenin, nominating it as a highly promising supplementary agent to be considered in the treatment of AP, and even as a protective agent against the damages induced by disease., Competing Interests: CONFLICTS OF INTEREST: No potential conflict of interest relevant to this article was reported., (Copyright © 2019, the Korean Surgical Society.)

Thermal skin burns cause local injury as well as triggers acute systemic inflammation response where the imbalance between oxidative and antioxidative system occurs. As an alternative treatment, various medicinal herbs are used to treat burn injuries in many countries. In this study, the possible protective role of oral or topical Myrtle (Myrtus communis L.) treatment against burn-induced damage was investigated. The dorsum of the Wistar Albino rats was shaved and exposed to 90 °C water bath in burn group or 25 °C water bath in control group for 10 s under ether anesthesia. Myrtle extract was applied 100 mg/kg/day for 2 days either orally or topically. In skin samples; malondialdehyde and glutathione levels, catalase, superoxide dismutase, nitric oxide and tissue factor activities were determined. Skin tissues were also examined by light microscopy. Severe thermal skin burn injury caused a significant decrease in glutathione level, superoxide dismutase, catalase and tissue factor activities as well as nitric oxide level, which was accompanied with significant increases in skin malondialdehyde level. Myrtle treatment reversed all these biochemical indices except topical Myrtle treated group's nitric oxide level, as well as histopathological alterations, which were induced by thermal trauma. Both oral and topical Myrtle extract treatment was found to have protective role in the burn induced oxidative injury, which may be attributed to the potential antioxidant effect of Myrtle. As a conclusion, Myrtle significantly diminishes burn-induced damage in skin., (Copyright © 2019 Elsevier Ltd and ISBI. All rights reserved.)

Radiotherapy (RT) for prostate cancer (PC) can cause erectile dysfunction (ED) by damaging neurovascular structures with oxidative stress. In this study, we evaluated the effects of resveratrol, an antioxidant, on post-RT ED. Fifty rats in five groups were evaluated; control (C), prostate-confined radiotherapy with short- and long-term vehicle or resveratrol treatment. Cavernosal tissues were obtained to analyze glutathione (GSH), nitric oxide (NO), cyclic guanosine monophosphate (cGMP), 8-hydroxy-2'-deoxy-guanosine (8-OHdG) levels and superoxide dismutase (SOD), caspase-3 activities, sirtuin-1, Foxo-3, nNOS, and eNOS protein expressions. Intracavernosal pressures (ICP) were measured for the long-term treatment group. In the RT + long-term vehicle treatment group, tissue GSH, NO, cGMP, and SOD activity were decreased while 8-OHdg levels and caspase-3 activities were increased. Radiotherapy caused a decrease in sirtuin-1, nNOS, and eNOS protein expressions. These parameters were reversed by resveratrol treatment. Foxo-3 protein expressions were unaltered in the RT + short-term vehicle treatment group and started to increase as a defense mechanism in the RT + long-term vehicle group; however, resveratrol treatment caused a significant increase in Foxo-3 expressions. Resveratrol preserved the metabolic pathways involved in erectile function and provided functional protection. Resveratrol can be used as a supplementary agent in patients undergoing radiotherapy to preserve erectile function.

Objectives: To examine the possible protective effect of quercetin (QT), which is well known for its antioxidant and protective effects in circumstances of oxidative stress, on urinary bladder tissue in a rat model of ischemia/reperfusion (I/R) injury, which is a known factor for the development of lower urinary tract dysfunction partly mediated by the generation of free radicals causing oxidative damage., Methods: Thirty male Sprague-Dawley rats were subjected to I/R injury through clamping the abdominal aorta for 30 min and then allowing reperfusion for the next 60 min. Quercetin (20 mg/kg; subcutaneously) or vehicle were given before ischemia and just before reperfusion. Findings of the isometric contraction studies in the organ bath and of the histological examinations along with oxidative stress markers were evaluated in bladder tissues., Results: Increased malondialdehyde (MDA) levels and myeloperoxidase (MPO) activities and decreased glutathione (GSH) levels and superoxide dismutase (SOD) activities in the I/R group were reduced by QT treatment. In the I/R group, pro-apoptotic marker caspase-3 was increased and anti-apoptotic bcl-2 protein was decreased, while QT treatment significantly reversed these parameters. In the I/R group contractile responses of the bladder strips to carbachol were significantly lower than those of the control group, which were reversed by QT treatment., Conclusion: Quercetin treatment protects bladder tissue contractility against acute I/R injury by decreasing oxidative stress and apoptosis induced by I/R., (© 2015 Wiley Publishing Asia Pty Ltd.)

Objective: To evaluate the protective effects of melatonin (Mel) on an ethylene glycol (EG)-induced nephrolithiasis model in rats., Materials and Methods: Thirty-two Wistar albino rats were divided into 4 groups: control, EG, prevention Mel (Mel + EG + Mel), and therapeutic Mel (EG + Mel). EG (0.75%) was added to drinking water to create nephrolithiasis model. The EG group received EG and the Mel + EG + Mel group received both EG and Mel for 8 weeks. In the EG + Mel group, EG is given for 8 weeks and Mel is given for the last 4 weeks of the experiment. At the end of experimental period, urine, blood samples, and tissues were collected., Results: In 24-hour urine samples, calcium, citrate, and creatinine levels were decreased and oxalate levels were increased in the EG group, whereas Mel prevention and Mel treatment reversed these parameters back to control levels. Malondialdehyde, glutathione activities, myeloperoxidase, superoxide dismutase levels, and caspase-3 activity showed improvements in the Mel-treated groups when compared with the EG group. 8-Hydroxydeoxyguanosine, matrix metalloproteinase 9 levels, N-acetyl-β-glucosaminidase activity, and osteopontin mRNA expression were elevated in the EG group and decreased back to control levels in the Mel + EG + Mel and EG + Mel groups. Histological examination showed improvement in the Mel-treated groups when compared with the EG group., Conclusion: Mel can prevent crystalluria and kidney damage due to crystal formation and aggregation. It can be considered as a potential prophylactic and protective agent in high-risk patients with urinary stone formation or recurrence if supported by further clinical studies., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To compare bone healing in mandibular vertical body osteotomies (MVBO) after fixation with a resorbable 2.0mm-profile fixation system in the first and third postoperative months in rabbits., Methods: Twenty hemimandibles of ten rabbits were divided into two groups according to duration of resorbable fixation-one or three months. The MVBOs were performed and one four-hole, resorbable, 2.0mm mini-plate fixation system was used on each side. The computed tomography (CT) scans, scanning electron microscopy (SEM), and histomorphometric outcomes of groups I and II were compared., Results: Significant differences were found between the one- and three- month assessments in terms of newly formed bone ratio values (p<0.05). There was more new bone formation at the third month on both the CT and histomorphometric examinations. A better adaptation of the bone tissues to the resorbable mini-plate and screws was observed on SEM at three months., Conclusion: The resorbable mini-plates provided a fixation stable enough to allow immediate oral alimentation and callus formation in both groups.

Treatment for dental avulsion cases is early or late replantation of the traumatized teeth. Prognosis of the replanted tooth depends on the level of periodontal injury. Adipose tissue stem cells (ATSCs) were reported to improve periodontal ligament tissue (PDL) regeneration. Fibrin sealant (FS) contains thrombin and fibrinogen to form an adhesive fibrin clot routinely used in surgical procedures. Here, we aimed to investigate the effects of ATSCs + FS treatment on healing of PDL after tooth replantation in a rat model. After 60 min of extraction, maxillary central incisor teeth were replanted with ATSCs + FS. Two months later, the rats were sacrificed and hemimaxilla blocks were dissected out for histological analysis. The results showed that there was a significant improvement in histological findings of ATSCs + FS treated group compared to only FS treated and non-treated groups corresponding to reduced inflammatory resorption and increased new PDL formation. Furthermore, the ankylosis levels were lowered after ATSCs + FS treatment. Singular use of FS improved PDL healing moderately. Our results indicated that ATSCs + FS treatment improves PDL healing after tooth replantation suggesting a new therapeutic potential in the treatment of dental avulsion cases.

Estrogen or combinational hormone therapy can protect to menopausal symptoms but exogenous estrogen therapy has some potential risks which in turns lead to the appearance of various diseases. In recent years plants with high phytoestrogen content are recommended as therapeutic agents for postmenopausal hormonal treatment. In this research, we investigated the effects of Momordica charantia (MC) on the estrogen production and E2 as well as anti-oxidative and anti-apoptotic role on the ovariectomy rat model. The rats were ovariectomized and fed on 2 g/kg of fruit extra of MC for 30 days by gavage. 17-β estradiol (E2) and 8-OHdG levels in serum, markers of oxidative damage of ROS and ESRα, ESRβ and NF-kB gene levels were measured in uterus horn tissue. Caspase-3, caspase-9, TNF-α, IL-6, IL-10, Bcl-2 and Nf-kB proteins expression were assessed by western blotting. Structural changes in tissue were examined with H&E staining. MC administration also stimulated the E2 production and ESRα/ESRβ gene levels and the inhibited oxidative damage. Furthermore, MC treatment enhanced anti-apoptotic and anti-inflammatory process and tissue regeneration. Data herein support that MC directly regulates uterine estrogen response and may serve as a new phytoestrogenic substance for the treatment of post-menopausal symptoms.

Aim: To compare bacterial biofilm colonization in lacrimal stents following external dacryocystorhinostomy (EX-DCR), endoscopic dacryocystorhinostomy (EN-DCR), and transcanalicular dacryocystorhinostomy (TC-DCR) with multidiode laser., Methods: This prospective study included 30 consecutive patients with nasolacrimal duct obstruction who underwent EXT-, EN-, or TC-DCR. Thirty removed lacrimal stent fragments and conjunctival samples were cultured. The lacrimal stent biofilms were examined by scanning electron microscopy (SEM)., Results: Eleven (36.7%) of the 30 lacrimal stent cultures were positive for aerobic bacteria (most commonly Staphylococcus epidermidis and Pseudomonas aeruginosa). However anaerobic bacteria and fungi were not identified in the lacrimal stent cultures. Twenty-seven (90%) patients had biofilm-positive lacrimal stents. The conjunctival culture positivity after the DCR, biofilm positivity on stents, the grade of biofilm colonization, and the presence of mucus and coccoid and rod-shaped organisms did not significantly differ between any of the groups (P>0.05). However, a significant difference was found when the SEM results were compared to the results of the lacrimal stent and conjunctival cultures (P<0.001)., Conclusion: Type of dacryocystorhinostomy (DCR) surgery did not affect the biofilm colonization of the lacrimal stents. SEM also appears to be more precise than microbiological culture for evaluating the presence of biofilms on lacrimal stents.

Background: This study was designed to determine the possible protective effect of captopril treatment against oxidative damage in heart and lung tissues induced by burn injury., Methods: Under ether anesthesia, the shaved dorsum of Wistar albino rats was exposed to 90°C water bath for 10 seconds. Captopril was administered intraperitoneally (10 mg/kg) after the burn injury and repeated twice daily. In the sham group, the dorsum was dipped in a 25°C water bath for 10 seconds. At the end of the 24 hours, echocardiographic recordings were performed, then animals were decapitated and heart and lung tissue samples were taken for the determination of tumor necrosis factor-α (TNF-α) as a pro-inflammatory cytokine, malondialdehyde and glutathione levels and myeloperoxidase, caspase-3, and Na+,K+-ATPase activity in addition to the histological analysis., Results: Burn injury caused significant alterations in left ventricular function. In heart and lung tissues, TNF-α and malondialdehyde levels and myeloperoxidase and caspase-3 activities were found to be increased, while glutathione levels and Na+, K+-ATPase activity were decreased due to burn injury. Captopril treatment significantly elevated the reduced glutathione level and Na+, K+-ATPase activity, and decreased cytokine and malondialdehyde levels and myeloperoxidase and caspase-3 activities., Conclusion: Captopril prevents burn-induced damage in heart and lung tissues and protects against oxidative organ damage.

Objective: To evaluate the effects of the immunosuppressant tacrolimus as an antioxidant and analyze the histopathologic changes in rat uteri exposed to experimental ischemia-reperfusion (I/R) injury., Design: Experimental study., Setting: Experimental surgery laboratory in a university., Animal(s): Twenty-eight female rats exposed to experimentally induced uterine I/R injury., Intervention(s): Group I: control group; group II: uterine I/R injury-induced group; group III: pre-ischemia tacrolimus group; group IV: post-ischemia tacrolimus group., Main Outcome Measure(s): Uterine tissue malondialdehyde (MDA) level as a marker of lipid peroxidation and glutathione (GSH) level and superoxide dismutase (SOD) and catalase (CAT) activities as markers of tissue antioxidant capacity; histopathologic examination of all uterine rat tissue., Result(s): Following aortic I/R injury, MDA levels were significantly increased whereas GSH levels and CAT and SOD activities were found to be decreased compared with control animals. MDA levels were found to recover prominently after the administration of tacrolimus in both groups III and IV. Administration of tacrolimus improved uterine GSH levels and CAT activity in the tacrolimus-treated groups., Conclusion(s): Our results indicate that tacrolimus reduces oxidative damage in rat uteri exposed to I/R injury induced by distal abdominal aortic occlusion. Histologic evaluation reveals that tacrolimus attenuates the inflammatory response and protects the tissue damage induced by I/R injury., (Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Spinal cord injury (SCI) leads to an inflammatory response and generates oxidative stress, which has deleterious effects on the function of several organ systems, including the urinary bladder. The present study was designed to investigate the putative beneficial effect of quercetin against SCI-induced bladder damage., Materials and Methods: 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 20 mg/kg quercetin or vehicle 15 min post injury and repeated twice daily for 7 d. After decapitation, bladder strips were placed in organ bath and isometric contractions to carbachol (10(-8) to10(-4) M) were recorded. In order to examine oxidative tissue injury, luminol chemiluminescence, nitric oxide, malondialdehyde, and glutathione levels and superoxide dismutase, myeloperoxidase, and caspase 3 activities of bladder tissues were measured along with histologic evaluations. Proinflammatory cytokines tumor necrosis factor α, interleukin 1β, and interleukin 6 were also assayed in blood samples., Results: In the injured animals, the contractile responses of the bladder strips were lower than those of the control group and were reversed by treatment with quercetin. On the other hand, increase in nitric oxide, malondialdehyde, luminol chemiluminescence levels, and myeloperoxidase and caspase 3 activities of tissues in the SCI group were significantly reversed by quercetin treatment. Similarly, plasma cytokine levels, which were elevated in the vehicle-treated SCI group, were reduced with quercetin treatment. Furthermore, treatment with quercetin also prevented the depletion of tissue glutathione levels and superoxide dismutase activity seen in the SCI group., Conclusions: According to the results, quercetin exerts beneficial effects against SCI-induced oxidative damage through its anti-inflammatory and antioxidant effects., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Oxidative stress has been implicated in various pathological processes including burn induced multiple organ damage. This study investigated the effects of lycopene treatment against oxidative injury in rats with thermal trauma. Under ether anesthesia, shaved dorsum of the rats was exposed to 90°C bath for 10s to induce burn and treated either vehicle (olive oil) or lycopene (50mg/kg orally). Rats were decapitated 48 h after injury and the tissue samples from lung and kidney were taken for histological analysis and the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT) and caspase-3 activities. Proinflammatory cytokines, TNF-α and IL-1β, were assayed in blood samples. Severe skin scald injury caused a significant decrease in GSH levels, SOD and CAT activities, and significant increases in MDA levels, MPO and caspase-3 activities of tissues. Similarly, plasma TNF-α and IL-1β were elevated in the burn group as compared to the control group. Lycopene treatment reversed all these biochemical indices. According to the findings of the present study, lycopene possesses antiinflammatory, antiapoptotic and antioxidant effects that prevents burn-induced oxidative damage in remote organs., (Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.)

Aims: We evaluated effects of BoNT-A injections on bladder function and histomorphology in a male-rat-overactive-bladder model, created by partial urethral obstruction., Methods: A total of 45 male Sprague-Dawley rats were separated into 5 groups. Partial urethral obstruction (PUO) was created in all rats except the control group. At the 6th week after PUO, intradetrusor injections of 50 µl of saline (2 sham groups) or 50 µl BoNT-A (2 treatment groups) was performed. Treatment and sham groups were studied 5 and 30 days after injection and neuropharmacological and histomorphological findings on bladder tissues were compared to the control group., Results: Bladder muscle hypertrophy and connective tissue increase were detected at 5th and more prominent at 30th day after saline injection. Intradetrusor BoNT-A injection significantly reduced PUO-induced histological changes in the bladder tissue both at 5th and 30th day after injection. At 5th day after saline injection, a significantly increased contractile response to electrical field stimulation (EFS) and carbachol were recorded in the saline group and this effect disappeared at 30th day. There was no statistically significant difference between BoNT-A and control groups in terms of contractile responses to EFS and carbachol, both at 5th and 30th days., Conclusion: Partial urethral obstruction induces increased bladder tissue contractile responses to neurogenic and pharmacological stimulation and intradetrusor BoNT-A injections decrease these responses at 5th days after injection. As the unique finding of this study, intradetrusor BoNT-A injections appear to decrease bladder fibrosis secondary to PUO in the male rat model., (Copyright © 2012 Wiley Periodicals, Inc.)

This study investigated the effect of Urtica dioica, known as stinging nettle, seed oil (UDO) treatment on colonic tissue and blood parameters of trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. Experimental colitis was induced with 1 mL of TNBS in 40% ethanol by intracolonic administration with a 8-cm-long cannula with rats under ether anesthesia, assigned to a colitis group and a colitis+UDO group. Rats in the control group were given saline at the same volume by intracolonic administration. UDO (2.5 mL/kg) was given to the colitis+UDO group by oral administration throughout a 3-day interval, 5 minutes later than colitis induction. Saline (2.5 mL/kg) was given to the control and colitis groups at the same volume by oral administration. At the end of the experiment macroscopic lesions were scored, and the degree of oxidant damage was evaluated by colonic total protein, sialic acid, malondialdehyde (MDA), and glutathione levels, collagen content, tissue factor activity, and superoxide dismutase and myeloperoxidase activities. Colonic tissues were also examined by histological and cytological analysis. Pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-1β, and interleukin-6), lactate dehydrogenase activity, and triglyceride and cholesterol levels were analyzed in blood samples. We found that UDO decreased levels of pro-inflammatory cytokines, lactate dehydrogenase, triglyceride, and cholesterol, which were increased in colitis. UDO administration ameliorated the TNBS-induced disturbances in colonic tissue except for MDA. In conclusion, UDO, through its anti-inflammatory and antioxidant actions, merits consideration as a potential agent in ameliorating colonic inflammation.

We report a family with Marie Unna hereditary hypotrichosis (MUHH) from Turkey. MUHH is a distinct form of scalp and body hair loss characterized by the absence or scarcity of scalp hair, eyebrows, and eyelashes at birth. Coarse wiry hair begins to grow during childhood. Around puberty, progressive hair loss occurs in the affected patients. Recently, mutations were identified in U2HR, an inhibitory upstream open reading frame in the 5'-untranslated region of the human hairless gene (HR) as the underlying cause of MUHH. We are presenting hair loss of eyebrows in a Turkish family comprising eight affected and seven unaffected individuals. The pedigree is compatible with autosomal dominant inheritance. Linkage and haplotype analyses confirmed linkage of this family to the MUHH locus at cytoband 8p21. By sequencing U2HR, we identified the mutation c.2T>C (M1T) in all affected family members. We concluded that there may be considerable clinical variations in MUHH, and that eyebrow loss is an important clue for accurate diagnosis., (Copyright © 2010 Wiley-Liss, Inc.)

Hyperglycemia is a common defining feature in the development of endothelial dysfunction which plays a key role in the pathogenesis of both type 1 and type 2 diabetes. Caveolin-1 is the main structural component of caveolae which might be involved in the pathophysiology of macrovascular complications of diabetes. In this study we aimed to observe the effect of caveolin-1 on functional responses of aorta and corpus cavernosum in the streptozotocin and fructose-induced diabetes groups. Type 1 diabetes was induced by intraperitoneal administration of streptozotocin (60 mg/kg),. Type 2 diabetes by adding fructose in the rat's drinking water (10% (w/v)) for 8 weeks. For insulin treatment; rats were treated with insulin (6 U/kg) for 8 weeks. In Type I and Type II diabetic groups the contractile responses of corpus cavernosum strips to phenylephrine (EC(50):1.82 x 10(-5)M;1.47 x 10(-5)M, respectively)and relaxation responses to acetylcholine (EC(50):7.5 x 10(-5)M;4.48 x 10(-5)M, respectively)were significantly impaired. Contractile responses of aorticstrips to phenylephrine in diabetic groups were markedly decreased (EC(50):3.7.10(-7)M;2.61.10(-7)M respectively) and dose-dependent relaxation responses to acetylcholine were also attenuated (EC(50):3.23.10(-6)M; 2.0.10(-6)M respectively). Treatment with insulin improved the functional responses in the aorta and corpus cavernosum. Protein expression of caveolin-1 was increased in the aorta and corpus cavernosum of the diabetic groups, but this increase seen in the streptozotocin group was more significant than the fructose group. Our findings indicate that an attenuation of the functional responses in both diabetes groups were probably associated with an enhanced expression of caveolin-1, and therefore a decrease in the eNOS activity with a concomitant decrease in NO synthesis., (Copyright (c) 2010 Elsevier B.V. All rights reserved.)

To elucidate the putative neuroprotective effects of ghrelin in subarachnoid hemorrhage (SAH)-induced brain injury, Wistar albino rats (n = 54) were divided into sham-operated control, saline-treated SAH, and ghrelin-treated (10 microg/kg/d IP) SAH groups. The rats were injected with blood (0.3 mL) into the cisterna magna to induce SAH, and were sacrificed 48 h after the neurological examination scores were recorded. In plasma samples, neuron-specific enolase (NSE), S-100beta protein, TNF-alpha, and IL-1beta levels were evaluated, while forebrain tissue samples were taken for the measurement of malondialdehyde (MDA), glutathione (GSH), reactive oxygen species levels, myeloperoxidase (MPO), Na(+)-K(+)-ATPase activity, and DNA fragmentation ratio. Brain tissue samples containing the basilar arteries were obtained for histological examination, while cerebrum and cerebellum were removed for the measurement of blood-brain barrier (BBB) permeability and brain water content. The neurological scores were impaired at 48 h after SAH induction, and SAH caused significant decreases in brain GSH content and Na(+)-K(+)-ATPase activity, and increases in chemiluminescence, MDA levels, and MPO activity. Compared with the control group, the protein levels of NSE, S-100beta, TNF-alpha, and IL-1beta in plasma were also increased, while ghrelin treatment prevented all SAH-induced alterations observed both biochemically and histopathologically. The results demonstrate that ghrelin alleviates SAH-induced oxidative brain damage, and exerts neuroprotection by maintaining a balance in oxidant-antioxidant status, by inhibiting proinflammatory mediators, and preventing the depletion of endogenous antioxidants evoked by SAH.

The neuroprotective effect of alpha lipoic acid (ALA; 100 mg/kg, po), a dithiol antioxidant, on experimentally induced subarachnoid hemorrhage (SAH) was assessed in Wistar albino rats. Neurological examination scores recorded at the 48th h of SAH induction were increased in SAH groups, which were accompanied with significant increases in the formation of reactive oxygen species, DNA fragmentation ratios, malondialdehyde levels and myeloperoxidase activity, while significant decreases in the brain glutathione content and Na(+), K(+)-ATPase activity were observed. On the other hand, ALA treatment reversed all these biochemical indices as well as SAH-induced histopathological alterations. Increased brain edema, impaired blood-brain-barrier permeability and neurological scores were also improved by ALA treatment. The results demonstrate that ALA exerts neuroprotective effects via the enhancement of endogenous antioxidant enzyme activity, the inhibition of neutrophil accumulation and free radical generation, suggesting a therapeutic potential in reducing secondary injury after SAH in patients.

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 2009 Elsevier B.V. All rights reserved.)

Background: Oxidative stress is a mediator of secondary injury to the spinal cord following trauma., Objective: To investigate the putative neuroprotective effect of alpha-lipoic acid (LA), a powerful antioxidant, in a rat model of spinal cord injury (SCI)., Methods: Wistar albino rats were divided as control, vehicle-treated SCI, and LA-treated SCI groups. 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 50 mg/kg LA or saline at 30 minutes postinjury by intraperitoneal injection. At 7 days postinjury, neurologic examination was performed, and rats were decapitated. Spinal cord samples were taken for histologic examination or determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity, and DNA fragmentation. Formation of reactive oxygen species in spinal cord tissue samples was monitored by using a chemiluminescence (CL) technique., Results: SCI caused a significant decrease in spinal cord GSH content, which was accompanied with significant increases in luminol CL and MDA levels, MPO activity, and DNA damage. Furthermore, LA treatment reversed all these biochemical parameters as well as SCI-induced histopathologic alterations. Conversely, impairment of the neurologic function caused by SCI remained unchanged., Conclusion: The present study suggests that LA reduces SCI-induced oxidative stress and exerts neuroprotection by inhibiting lipid peroxidation, glutathione depletion, and DNA fragmentation.

Radiation-induced enteritis is a well-recognized sequel of therapeutic irradiation. Therefore we examined the radioprotective properties of Punica granatum peel extract (PPE) on the oxidative damage in the ileum. Rats were exposed to a single whole-body X-ray irradiation of 800 cGy. Irradiated rats were pretreated orally with saline or PPE (50 mg/kg/day) for 10 days before irradiation and the following 10 days, while control rats received saline or PPE but no irradiation. Then plasma and ileum samples were obtained. Irradiation caused a decrease in glutathione and total antioxidant capacity, which was accompanied by increases in malondialdehyde levels, myeloperoxidase activity, collagen content of the tissue with a concomitant increase 8-hydroxy-2'-deoxyguanosine (an index of oxidative DNA damage). Similarly, pro-inflammatory cytokines (TNF-alpha, IL-1beta and IL-6) and lactate dehydrogenase were elevated in irradiated groups as compared to control. PPE treatment reversed all these biochemical indices, as well as histopathological alterations induced by irradiation. Furthermore, flow cytometric measurements revealed that leukocyte apoptosis and cell death were increased in irradiated animals, while PPE reversed these effects. PPE supplementation reduced oxidative damage in the ileal tissues, probably by a mechanism that is associated with the decreased production of reactive oxygen metabolites and enhancement of antioxidant mechanisms. Adjuvant therapy of PPE may have a potential to support a successful radiotherapy by protecting against radiation-induced enteritis.

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.

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.

Epidemiological and experimental studies have demonstrated that cigarette smoking intensifies gastric ulceration. Although nicotine can act as an anxiolytic and antidepressant, its withdrawal may also lead to increased anxiety and depression. In order to associate the toxic actions of nicotine on gastric mucosa with alterations of anxiety level and to evaluate the impact of nicotine withdrawal on the anxiety level and the severity of ulcer, an acetic acid-induced ulcer model was used. Male Sprague-Dawley rats were given either tap water or nicotine bitartarate (50μg/ml in drinking water) for 15 days, while another group of rats had 5 days of withdrawal following 10 days of nicotine treatment. Ulcer was induced by acetic acid on the 15th day of the treatments, and the rats were followed for 3 days until they were decapitated and the gastric tissues were obtained. Using the hole-board test, basal anxiety levels measured on the first day of the treatments were compared with the measurements made at the early and late phases of ulcer induction. Chronic administration of nicotine did not have a potentiating effect on acetic acid-induced gastric ulcer, since the gastric injury, as assessed by both macroscopic and microscopic evaluation and increased gastric myeloperoxidase activity indicating neutrophil recruitment, was not exaggerated or attenuated by nicotine intake. On the other hand, nicotine withdrawal attenuated gastric mucosal injury, despite an increased level of anxiety. Smoking cessation, which triggers the onset of depressive symptoms with nicotine withdrawal, still has a worthwhile positive effect on the gastric mucosa., (Copyright © 2008 Elsevier B.V. All rights reserved.)

The possible protective effects of resveratrol (RVT) against cardiotoxicity were investigated in Wistar albino rats treated with saline, saline+doxorubicin (DOX; 20 mg/kg) or RVT (10 mg/kg)+DOX. Blood pressure and heart rate were recorded on the 1st week and on the 7th week, while cardiomyopathy was assessed using transthoracic echocardiography before the rats were decapitated. DOX-induced cardiotoxicity resulted in decreased blood pressure and heart rate, but lactate dehydrogenase, creatine phosphokinase, total cholesterol, triglyceride, aspartate aminotransferase and 8-OHdG levels were increased in plasma. Moreover, DOX caused a significant decrease in plasma total antioxidant capacity along with a reduction in cardiac superoxide dismutase, catalase and Na+,K+-ATPase activities and glutathione contents, while malondialdehyde, myelopreoxidase activity and the generation of reactive oxygen species were increased in the cardiac tissue. On the other hand, RVT markedly ameliorated the severity of cardiac dysfunction, while all oxidant responses were prevented; implicating that RVT may be of therapeutic use in preventing oxidative stress due to DOX toxicity.

Background: The aim of this study was to assess the possible protective effect of proanthocyanidin against cerulein-induced acute pancreatic inflammation (AP) and oxidative injury., Methods: Sprague-Dawley rats were pretreated with proanthocyanidine (100 mg/kg, orally) or saline 15 min before cerulein was given by 20 µg/kg subcutaneously at 1-h intervals within 4 hours. Six hours after cerulein or saline injections, the animals were killed by decapitation. Blood samples were collected to analyze amylase, lipase, and proinflammatory cytokines (TNF-α and IL-1b). Pancreas tissues were taken for the determination of tissue glutathione (GSH) and malondialdehyde (MDA) levels, Na + , K + -ATPase and myeloperoxidase (MPO) activities. Formation of reactive oxygen species in pancreatic tissue samples was monitored by using chemiluminescence (CL) technique with luminol and lucigenin probes, while the extent of tissue injury was analyzed microscopically., Results: Acute pancreatitis caused a significant decrease in tissue GSH level and Na + , K + -ATPase activity, which was accompanied with significant increases in the pancreatic MDA, luminol and lucigenin chemiluminescences (CL) levels and MPO activity. Similarly TNF-α and IL-1β levels were elevated in the pancreatic group as compared to control group. On the other hand, proanthocyanidin treatment reversed all these biochemical indices, as well as histopathological alterations that were induced by cerulein., Conclusions: Proanthocyanidine can ameliorate pancreatic injury induced by cerulein in rats, this result suggests that proanthocyanidin may have utility in treating acute pancreatititis.

The impact of sex dimorphism on chronic renal failure (CRF)-induced oxidative multiorgan damage and the effects of estradiol (E(2)) loss and E(2) 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 microg/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-alpha of male rats was abolished when the animals were treated with E(2), while OVX exaggerated TNF-alpha response. In OVX and male rats with CRF, E(2) 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 E(2) treatment. Similarly, increased levels of myeloperoxidase activity, lucigenin chemiluminescence, and collagen in most of the tissues were reversed by E(2) 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 E(2), 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.

Introduction: This study aims to investigate gadolinium chloride (Gd) pre-treatment with/without splenectomy (Splx) in the setting of renal ischemia/reperfusion (IR) injury in rats., Materials and Methods: Under anesthesia, male Wistar albino rats with or without splenectomized (Splx) were right nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 3 h of reperfusion. Gadolinium chloride (10 mg kg(-1)) or saline was administered 24 hours prior to ischemia via penile vein. Right nephrectomy and intravenous saline administration was performed in the control group. At the end of the reperfusion period, following decapitation, kidney samples were taken for histological examination or determination of renal malondialdehyde (MDA) and glutathione (GSH) levels and myeloperoxidase (MPO) and Na(+)-K(+) ATPase activities. Creatinine, blood urea nitrogen (BUN), lactate dehydrogenase (LDH), TNF-alpha, and IL-1 beta were assayed in the serum samples., Results: Ischemia/reperfusion caused significant increases in the serum TNF-alpha, IL-1 beta, BUN, creatinine, AST, ALT, LDH, and tissue MDA levels and MPO activity, while either Gd pre-treatment or Splx decreased these parameters significantly. On the other hand, IR induced a decrease in the tissue GSH, and Na(+)-K(+) ATPase activity was restored by both gadolinium and Splx. Furthermore, histopathological alterations induced by IR were also reversed., Conclusion: The extent of renal IR injury depends on the pro-inflammatory cytokine response. Gd pre-treatment decreases macrophage-derived cytokine secretion and thereby effectively limits the extent of renal IR injury in rats similar to Splx. Further studies needed to define an optimal way of decreasing macrophage-derived cytokine release due to the clinical limitations of Gd.

Cysteinyl leukotrienes play a part in inflammatory reactions such as asthma and inflammatory bowel diseases. The leukotrienes exert their actions by binding to and activating various receptors. Montelukast, a leukotriene receptor antagonist, which is used in the treatment of asthma has been shown to be effective in inhibiting the action or formation of leukotrienes. Many skin disorders, such as atopic dermatitis and psoriasis, worsen during stress and seem to be related to infiltration and activation of mast cells that are releasing vasoactive and pro-inflammatory mediators. The aim of the present study was to investigate the effects of montelukast on the degranulation of mast cells in the dermis that is induced by water avoidance stress (WAS). Wistar albino rats were divided into four groups of 8 animals each. Control rats were injected with (1) the vehicle solution or (2) the montelukast solution in the absence of WAS. (3) the WAS group of rats was administered vehicle solution following WAS exposure for 2h daily for 5 days. (4) The WAS+ML group was administered montelukast 10mg/kg; i.p. following WAS exposure for 2h daily for 5 days. Dermal mast cell numbers were determined with toluidine blue and tryptase immunohistochemistry and observed using a light microscope. Numbers of both granulated and degranulated mast cells were significantly increased in the WAS group when compared to control rats. Montelukast treatment decreased the number of both mature granulated and degranulated mast cells in rats subjected to WAS. In conclusion, chronic montelukast treatment reduced WAS-induced infiltration and activation of mast cells in the dermis and may provide a useful therapeutic option in stress-induced skin disorders.

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.

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 (100 mg/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-alpha, IL-beta, 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-alpha, IL-beta, 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.

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 degrees C bath for 10 s to induce thermal trauma. Ghrelin, was administered subcutaneously (10 ng/kg/day) after the burn injury and repeated twice daily. Rats were decapitated at 6 h and 48 h after burn injury and blood was collected for the analysis of pro-inflammatory cytokines (TNF-alpha and IL-1beta), 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.

At the cellular level, spinal cord injury (SCI) provokes an inflammatory response that generates substantial secondary damage within the cord, but also may contribute to its repair. The aim of this study was to investigate the effects of inflammatory response associated with SCI in cutaneous wound healing and on expression of transforming growth factor-beta1 (TGF-beta1) and platelet-derived growth factor (PDGF)-A at the wound site in rats. At the 14th day analysis, the mean TGF-beta1 score in trauma group (I) was significantly lower than that in control group (C) (2.60 +/- 0.90 vs. 3.64 +/- 0.37, respectively; p < 0.05). The mean score for PDGF-A expression in group I was similar to the corresponding value in group C (2.42 +/- 0.74 vs. 2.94 +/- 0.72, respectively). Compared to group C, group I had significantly lower mean scores for epidermal and dermal regeneration, but higher mean scores for granulation tissue thickness and similar scores for angiogenesis. The dermal layer contains diffuse deposition of collagen fibers that are not organised as in control rat skin, and intraepidermal and subepidermal vasocongestion is distinct. Based on the results on the parameters evaluated in the study, experimental SCI in rats results in delay in wound healing and low intensity of TGF-beta1 in the dorsal wound-tissue specimens.

We investigated the role of montelukast (ML), a cysteinyl leukotriene-1 receptor antagonist, on the water avoidance stress (WAS)-induced degeneration of the rat gastric, ileal and colonic mucosa. One group of Wistar albino rats were exposed to chronic WAS (WAS group) 2h daily for 5 days. Another group was administered ML (10mg/kg; i.p.; WAS+ML group) following every WAS exposure for 5 days. Control rats were injected with the vehicle solution only. The stomach, ileum and colon were dissected and investigated for histopathological changes with a light microscope as well as for topographical changes with a scanning electron microscope. The levels of malondialdehyde (MDA, a biomarker of oxidative damage) and glutathione (GSH, a biomarker of protective oxidative injury) were also determined in all dissected tissues. In the WAS group, the stomach epithelium showed ulceration in some areas, dilatations of the gastric glands, degeneration of gastric glandular cells, and prominent congestion of the capillaries. In a similar fashion, degenerated epithelium and severe vascular congestions were observed in the ileum and colon. In all the tissues dense inflammatory cell infiltration and mast cell degranulation in mucosa were observed. The levels of MDA were significantly increased whereas those of GSH were significantly decreased in all test tissues in the WAS group compared to the control group. The morphology of gastric, ileal and colonic mucosa in WAS+ML group showed a significant amelioration showing a reduction in inflammatory cell infiltration and mast cell degranulation. Increased MDA and decreased GSH levels in the WAS group were also ameliorated with ML treatment. Based on the results, ML supplement seems attenuated inflammatory effects of WAS induction in gastrointestinal mucosa.

1. Oxygen free radicals are important components involved in the pathophysiological processes observed during ischaemia-reperfusion (I/R). The present study was designed to assess the possible protective effect of alpha-lipoic acid (ALA) on renal I/R injury. 2. Wistar albino rats were unilaterally nephrectomized and subjected to 45 min renal pedicle occlusion followed by 24 h reperfusion. Saline or ALA (100 mg/kg, i.p.) was administered 15 min prior to ischaemia and immediately before the reperfusion period. At the end of 24 h, rats were decapitated and trunk blood was collected. Creatinine, blood urea nitrogen (BUN) and lactate dehydrogenase (LDH) activity were measured in serum samples, whereas tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, 8-hydroxydeoxyguanosine (8-OHdG) and total anti-oxidant capacity (AOC) were assayed in plasma samples. 3. Kidney samples were taken for the determination of tissue malondialdehyde (MDA) and glutathione (GSH) levels, as well as Na(+)/K(+)-ATPase and myeloperoxidase (MPO) activity. The formation of reactive oxygen species in renal tissue samples was monitored using a chemiluminescence (CL) technique with luminol and lucigenin probes. Oxidant-induced tissue fibrosis was determined by tissue collagen content and the extent of tissue injury was analysed microscopically. 4. Ischaemia-reperfusion caused a significant increases in blood creatinine, BUN, LDH, IL-1beta, IL-6, TNF-alpha and 8-OHdG, whereas AOC was decreased. In kidney samples from the I/R group, MDA, MPO, collagen and CL levels were found to be increased significantly; however, glutathione levels and Na(+)/K(+)-ATPase activity were decreased. Conversely, ALA treatment reversed all these biochemical indices, as well as histopathological alterations induced by I/R. 5. In conclusion, these data suggest that ALA reverses I/R-induced oxidant responses and improves microscopic damage and renal function. Thus, it seems likely that ALA protects kidney tissues by inhibiting neutrophil infiltration, balancing the oxidant-anti-oxidant status and regulating the generation of inflammatory mediators.

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., ((c) 2008 S. Karger AG, Basel.)

We investigated the effect of aqueous garlic extract (AGE) on water avoidance stress (WAS)-induced degeneration of the gastric and ileal mucosa and liver parenchyma. Wistar albino rats were exposed to WAS (WAS group) for 5 days. After exposure of the animals to WAS, a 1 ml/kg aqueous garlic extract (AGE) was injected i.p. (WAS+AGE group). The stomach, ileum, and liver samples were investigated under light microscope for general morphology. Topography of gastric and ileal mucosa was investigated by scanning electron microscopy, and hepatocyte ultastructure by transmission electron micsroscopy. Malondialdehyde (MDA) and glutathione (GSH) levels of all tissues were also determined. In the WAS group, the epithelium of the stomach showed ulceration in some areas, dilatations of the gastric glands, and degeneration of gastric glandular cells. Severe vascular congestion and degeneration of ileal epithelium were observed. Prominent vascular congestion and dilated sinusoids, activated Kupffer cells with prominent morphology, dilated granular endoplasmic reticulum membranes, and focal picnotic nuclei were observed in liver parenchyma. AGE treatment reduced the degeneration of the gastric and ileal mucosa and liver parenchyma. Increased MDA levels and decreased GSH levels in the WAS group were reversed to control values after AGE treatment. Based on these results, AGE treatment significantly prevented WAS-induced degeneration in both morphology and biochemistry of gastrointestinal mucosa and liver parenchyma due to its potent free radical scavenging and antioxidant properties.

After intracolonic administration of trinitrobenzene sulphonic acid (TNBS), Sprague-Dawley rats were treated orally either with saline or erdosteine (100 mg/kg per day), a sulfhydryl-containing antioxidant, for 3 days. On the 4th day, rats were decapitated and distal colon was removed for the macroscopic and microscopic damage scoring, for the measurement of malondialdehyde (MDA), glutathione (GSH) and collagen levels, myeloperoxidase (MPO) activity, luminol and lucigenin chemiluminescence (CL) and DNA fragmentation. Lactate dehydrogenase (LDH) activity, tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, and antioxidant capacity were assayed in blood samples. Colitis caused significant increases in the colonic CL values, macroscopic and microscopic damage scores, MDA and collagen levels, MPO activity and DNA fragmentation, along with a significant decrease in tissue GSH level. Similarly, serum cytokines and LDH were elevated in the saline-treated colitis group as compared with the control group. On the other hand, erdosteine treatment reversed all these biochemical indices, and histopathologic alterations induced by TNBS, suggesting that erdosteine protects the colonic tissue via its radical scavenging and antioxidant activities.

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-alpha, IL-beta 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.

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-alpha 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-alpha 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.

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 10(10) 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.

This investigation elucidated the role of free radicals in naphthalene-induced toxicity and protection by Ginkgo biloba extract (EGb). BALB-c mice of either sex were administered with naphthalene (100 mg/kg; i.p.) for 30 days, along with either saline or EGb (150 mg/kg, orally). At the end of the experiment, following 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. In addition, proinflammatory cytokines (TNF-alpha and IL-beta) and total antioxidant capacity (AOC) were assayed in the plasma, while lactate dehydrogenase (LDH) activity was assayed in serum samples. The results revealed that naphthalene caused a significant decrease in GSH level, and significant increases in MDA level, MPO activity and collagen content of tissues. Similarly, plasma cytokines, as well as serum LDH activity, were elevated while AOC was decreased in the naphthalene group compared with the control group. On the other hand, EGb treatment reversed all these biochemical indices. The results demonstrate that EGb extract, by balancing the oxidant-antioxidant status and inhibiting the generation of proinflammatory cytokines and neutrophil infiltration, protects against naphthalene-induced oxidative organ injury.

In this study, we investigated the protective effect of β-glucan against nicotine induced oxidative damage in urinary bladder and kidney tissues. Wistar albino rats were injected i.p. with nicotine hydrogen bitartarate (0.6mg/kg daily for 21 days) or saline. β-Glucan (50mg/kg, p.o.) was administered alone or with nicotine injections for 21 days. After decapitation, the urinary bladder and kidney tissues were taken for the measurement of malondialdehyde (MDA) and glutathione (GSH) levels, and myeloperoxidase (MPO) activity. Tissue samples were also examined histologically. In serum samples MDA, GSH, BUN, creatinine, TNF-α levels and LDH activity were analyzed. Chronic nicotine administration caused a significant decrease in GSH levels and increases in MDA levels and MPO activity in kidney and bladder tissues, suggesting oxidative organ damage, which was also histologically verified. Furthermore, β-glucan restored the reduced GSH levels, while it significantly decreased MDA levels and MPO activity. Renal function tests, LDH and TNF-α levels, which were increased significantly due to nicotine administration, were decreased with β-glucan treatment. The present data suggest that β-glucan supplementation effectively counteracts the chronic nicotine toxicity and attenuates oxidative damage of bladder and kidney tissues possibly by its antioxidant effects., (Copyright © 2006 Elsevier B.V. All rights reserved.)

We studied the potential effects of taurine, a free radical scavenger, on chronic water avoidance stress (WAS)-induced degeneration of the mucosa of the urinary bladder in experimental rats. Wistar albino rats were exposed to WAS for 2h/day, for 5 days (WAS group). Before exposing them to WAS, taurine (50mg/kg) (WAS+taurine group) was injected intraperitonally into the animals. Samples of urinary bladder were then investigated by light and scanning electron microscopy. Lipid peroxidation and gluthathione levels were also measured in the urinary bladder. In the WAS-only group, inflammatory cell infiltration, increased number of mast cells in the mucosa and ulcerated areas were observed. In the WAS+taurine group, relatively normal urothelial topography with microvilli, moderate inflammatory cell infiltration and decreased numbers of mast cells in the mucosa were observed. The increased lipid peroxidation and decreased glutathione levels in WAS rats were reversed by taurine treatment. We conclude that taurine protects against WAS-induced oxidant urinary bladder injury, and thus may be a possible therapeutic agent against interstitial cystitis, the symptoms of which are aggravated by stress conditions.