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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).

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 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.)

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.

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.

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.

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

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

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

Oxygen free radicals are important components involved in pathophysiological tissue alteration observed during ischemia/reperfusion (I/R). This study was designed to determine the possible protective effect of aqueous garlic extract (AGE) on renal I/R injury. Wistar albino rats were unilaterally nephrectomized and subjected to 45 minutes of renal pedicle occlusion followed by 6 hours of reperfusion. AGE (1 mL/kg, i.p., corresponding to 500 mg/kg) or vehicle was administered twice: 15 minutes 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 levels of free radicals; renal malondialdehyde (MDA), an end product of lipid peroxidation; glutathione (GSH), a key antioxidant; and myeloperoxidase (MPO) activity, an index of tissue neutrophil infiltration. 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 revealed that I/R-induced nephrotoxicity, as evidenced by increases in blood urea and creatinine levels, was reversed by AGE treatment. The levels of free radicals, as assessed by the nitro blue tetrazolium test, were increased. Moreover, the decrease in GSH levels and the increases in MDA levels and MPO activity induced by I/R indicated that renal injury involves free radical formation. Treatment of rats with AGE (1 mL/kg) restored the reduced GSH levels, while it decreased free levels of radicals and MDA as well as MPO activity. Collagen contents of the kidney tissues increased by I/R were reversed back to the control levels with AGE. Since AGE administration reversed these oxidant responses and improved renal function and damage at the microscopic level, it seems likely that AGE protects kidney tissue against I/R-induced oxidative damage.

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.

The aim of the present study was to assess the role of endothelin (ET) in ischemia-reperfusion (I/R)-induced mucosal injury. Mucosal permeability ((51)Cr-EDTA clearance) and tissue myeloperoxidase (MPO) activity were significantly increased after 30 min of ischemia followed by 30 min of reperfusion. The I/R-induced increases in mucosal permeability and polymorphonuclear leukocyte (PMN) infiltration were significantly attenuated by pretreatments with ET(A) (BQ-485) and/or ET(B) (BQ-788) receptor antagonists. Monoclonal antibody (MAb) directed against intercellular adhesion molecule-1 (ICAM-1; MAb 1A29) and superoxide dismutase (SOD) pretreatments significantly attenuated the increased mucosal permeability and PMN infiltration in a similar manner as with ET receptor antagonists. Superior mesenteric artery blood flow was significantly reduced during the reperfusion period. Both ET receptor antagonists caused a significant rise in blood flow compared with an untreated I/R group. In conclusion, our data suggest that ET(A) and/or ET(B) receptors, ICAM-1, and superoxide play an important role in I/R-induced mucosal dysfunction and PMN infiltration. Furthermore, ET is involved in the pathogenesis of post-reperfusion-induced damage and beneficial effects of ET receptor antagonism are related to an improvement of disturbed blood flow during the reperfusion period.

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-infl ammatory cytokines TNF-α and IL-1β in rats undergoing hepatic ischemia reperfusion (Tab. 1, Fig. 2, Ref. 28). Text in PDF www.elis.sk [ABSTRACT FROM AUTHOR]