The role of alpha-tocopherol and allopurinol in lipid peroxidation and mitochondrial respiration in the ischemic rat liver

In the present study, the effects of alpha-tocopherol and allopurinol in liver ischemia and reperfusion injury on lipid peroxidation and mitochondrial respiratory function were investigated in rats. Ischemia was induced in the left and median liver lobes clamping the vessels for 90 minutes. After declamping reperfusion was continued for 60 minutes. Liver tissue was taken before and 90 minutes after ischemia and 60 minutes after reperfusion to measure lipid peroxides and mitochondrial respiratory function. In one group of rats alpha-tocopherol (10mg/kg) was given intraperitoneally for three consecutive days preoperatively and in the other group allopurinol (50mg/kg) was given intravenously 10 minutes before ischemia. alpha-Tocopherol caused inhibition of increase in lipid peroxides at reperfusion and improvement in lowering of mitochondrial respiratory function. This improvement was less than previously reported, probably due to not only reperfusion injury but also ischemic injury. Allopurinol, on the other hand, caused neither such inhibition nor such improvement, suggesting the other source of oxygen-derived free radicals than xanthine oxidase system.     

The role of oxygen-derived free radicals and the effect of free radical scavengers on skeletal muscle ischemia/reperfusion injury

The aim of this study was to clarify the role of oxygen-derived free radicals and the effect of free radical scavengers on skeletal muscle ischemia/reperfusion injury. Male Wistar rats were divided into a complete ischemia group (C-group) and an incomplete ischemia group (IC-group) and each animal was subjected to 2h of ischemia and 1h of reperfusion. In an attempt to decrease reperfusion injury, the rats were given free radical scavengers either as allopurinol 50 mg/kg for 2 days or as superoxide dismutase 60,000 units/kg plus catalase 500,000 units/kg. Tissue malondialdehyde, a product of lipid peroxidation, was measured as an indicator of free radicals, with higher levels indicating higher concentrations of free radicals. The malondialdehyde level in the gastrocnemius muscle after 1h of reperfusion increased significantly in both groups when compared to the levels before and 2h after ischemia, although there was no significant difference between the two groups. The water content of the gastrocnemius muscle and serum creatinine phosphokinase MM isoenzyme (CPK-MM) in both groups, and GOT in the C-group, increased significantly after 1h of reperfusion when compared the values before and 2h after ischemia. In the C-group, these values were significantly higher than in the IC-group. The administration of free radical scavengers suppressed the increase in malondialdehyde in the gastrocnemius muscle after reperfusion in both groups. The increase in water content and CPK-MM after reperfusion was also suppressed by free radical scavengers in the IC-group, but not in the C-group. These findings suggest that ischemic damage predominates in complete severe ischemia/reperfusion injury, whereas reperfusion injury predominates in incomplete mild ischemia/reperfusion injury.     

The Protective Effects of Ascorbic Acid against Renal Ischemia-Reperfusion Injury in Male Rats

There is increasing evidence to suggest that toxic oxygen radicals play an essential role in the pathogenesis of ischemia/reperfusion (I/R) injury in the kidney. This study was designed to investigate the effects of ascorbic acid (AA) in I/R-induced renal injury in rats. Thirty two male Sprague-Dawley rats were divided equally into four groups: group 1 (control; dissection of the right renal pedicle without nephrectomy), group 2 (sham operated; unilateral nephrectomy), group 3 (I/R; unilateral nephrectomy?+?I/R); and group 4 (AA+I/R; unilateral nephrectomy and I/R treated with ascorbic acid, 250mg kg^?1 i.p., for one hour prior to ischemia). On the 15th day following nephrectomy, groups 3 and 4 were subjected to 45 min of renal pedicle occlusion followed by 3 h of reperfusion. At the end of the treatment period, kidney samples were taken for histological examination or determination of the renal malondialdehyde (MDA) and glutathione (GSH) levels. Serum creatinine, blood urea nitrogen (BUN), and lactate dehydrogenase (LDH) concentrations were measured for the evaluation of renal function. I/R caused a significant decrease in GSH level, which was accompanied with a significant increase in MDA level of kidney tissues. Similarly, serum BUN and creatinine levels, as well as LDH, were elevated in the I/R group as compared to the control group. In group four, AA treatment reversed all the changes in these biochemical indices, as well as histopathological alterations normally induced by I/R. The findings imply that reactive oxygen species play a causal role in I/R-induced renal injury, and that AA exerts renoprotective effects, probably by radical scavenging and antioxidant activities.     

Oxygen free radicals and glutathione in hepatic ischemia/reperfusion injury

Oxygen free radicals have been implicated as mediators of ischemia/reperfusion injury in a variety of organs. We investigated the role of oxidative injury and endogenous hepatic glutathione (GSH) in liver cell injury associated with complete hepatic ischemia and reperfusion. Forty-five minutes of complete hepatic ischemia followed by reperfusion caused an increase in serum GPT and a fall in hepatic GSH but no increase in hepatic lipid peroxidation products. Chemical depletion of hepatic GSH with diethyl maleate did not cause hepatocellular injury but augmented hepatic ischemia/reperfusion-induced SGPT release and promoted lipid peroxidation. Pretreatment with the selective, membrane-permeable oxygen radical scavenger dimethyl sulfoxide protected against the ischemia/reperfusion-induced drop in hepatic GSH but did not reduce SGPT release in normal rats. In rats sensitized to oxidative injury by depletion of endogenous GSH with diethyl maleate the oxygen radical scavenger protected against ischemia/reperfusion-induced lipid peroxidation and reduced the release of SGPT. These findings suggest that the rich hepatic supply with endogenous GSH has a crucial role in the protection against oxygen radical injury following short periods of total hepatic ischemia. Oxygen radical injury only occurs after depletion of these endogenous GSH stores.     

Protective Effect of Melatonin Against Ischemia/Reperfusion-Induced Oxidative Remote Organ Injury in the Rat

Purpose Oxygen free radicals are considered to be important components involved in the pathophysiological tissue alterations observed during ischemia/reperfusion (I/R). Based on the potent antioxidant effects of melatonin, we investigated the putative protective role of melatonin against I/R-induced oxidative remote organ injury.Methods Wistar albino rats were subjected to 1 h of infrarenal aortic occlusion followed by 1 h of reperfusion to induce I/R damage. Melatonin (10 mg/kg, s.c.) or vehicle was administered twice, 15 min prior to ischemia and immediately before the reperfusion period (I/R + Mel or I/R groups). At the end of the reperfusion periods, the rats were decapitated and hepatic, ileal, and lung tissue samples were removed for biochemical analyses of: malondialdehyde (MDA), an end product of lipid peroxidation; the glutathione (GSH) levels, a key antioxidant; and the myeloperoxidase (MPO) activity, as an indirect index of neutrophil infiltration. The serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were measured to evaluate the liver function. The wet/dry lung weight ratio was calculated to determine the extent of lung damage.Results The results revealed the occurrence of I/R-induced oxidative organ damage, as evidenced by increases in the MDA and MPO activity, and a decrease in GSH. Furthermore the AST, ALT levels, and the wet/dry lung weight ratio, which all increased due to I/R, were all observed to decrease after melationin treatment.Conclusion Since melatonin administration reversed these oxidant responses, it seems likely that melationin has a protective effect against oxidative organ damage induced by I/R.     

Ebselen, a novel anti-oxidant compound, protects the rat liver from ischemia-reperfusion injury

The present study was designed to examine the in vivo effect of ebselen on reperfusion injury to the liver. Lipid peroxidation and glutathione (GSH) levels of the reperfused liver tissue, as well as hepatocellular damage (serum GOT, GPT, LDH, and histology) were examined. The production of thiobarbituric acid-reactive substance did not increase in the 60-min-reperfused liver tissue in the ebselen group. Ebselen completely suppressed the increase in lipid hydroperoxide production in the reperfused liver tissue. After the tissue GSH level was reduced by buthionine sulphoximine, ebselen failed to suppress the lipid peroxidation of the reperfused liver tissue. Serum levels of GOT, GPT, and LDH, histological analysis, and the tissue level of GSH clearly showed that ebselen protects the reperfused liver tissue, both structurally and functionally. We conclude that ebselen's primary effect on ischemia-reperfusion injury may be due to a GSH-peroxidase-like effect and/or the inhibitory effect of leukocyte infiltration. Received: 23 May 1996 Received after revision: 8 October 1996 Accepted: 28 October 1996     

Free radical scavengers to prevent reperfusion injury following experimental warm liver ischaemia. Is there a real physiological benefit?

Free radical scavengers have been utilized to prevent the consequences of ischemia, however, results do not seem conclusive. In our study we analyzed the blood flow, function, and histology of rat liver tissue after warm liver ischemia, in order to assess the effect of free radicals in liver reperfusion injury. N-acetyl cysteine (NAC), tocopherol, allopurinol, and superoxide dismutase (SOD), pharmacological agents expected to protect from injury mediated by free radicals, were investigated. Laser Doppler flowmetry and photometry were utilized to measure post-ischemic microcirculatory changes as an expression of ischemia-reperfusion injury in a model of segmental liver ischemia in the rat, with an ischemic time of 45 min. Galactose elimination capacity, ALT and histology were used to assess the functional and morphological consequences of ischemia after 24 h of reperfusion. The overall mean blood flow over 1 hour after reperfusion was of 33.9 % (SD 11.2) of the normal, non-ischemic control. NAC (31.2 % SD 10.9) did not show any protective effect and in some cases the effect seemed to be negative. Tocopherol (41.7 % SD 5.1) marginally improved post ischemic liver tissue blood flow. Treatment with allopurinol did not show any beneficial effects (37.5 % SD 14.2). Only animals treated with SOD showed an improvement of the post ischemic liver microcirculation (57.9 % SD 14.4)(P < 0.001) and function. Only SOD produced statistically significant differences in galactose elimination capacity, compared with those of the ischemic control group. This moderately protective effect of SOD is encouraging, however, the relevance of all these compounds in a broader pathophysiological setting remains unproven. Received: 24 August 1998 Received after revision: 14 December 1998 Accepted: 2 February 1999     

Glutathione protects the rat liver against reperfusion injury after prolonged warm ischemia

OBJECTIVE: To evaluate the potential of postischemic intravenous infusion of the endogenous antioxidant glutathione (GSH) to protect the liver from reperfusion injury following prolonged warm ischemia. BACKGROUND DATA: The release of reactive oxygen species (ROS) by activated Kupffer cells (KC) and leukocytes causes reperfusion injury of the liver after warm ischemia. Therefore, safe and cost-effective antioxidant strategies would appear a promising approach to prevent hepatic reperfusion injury during liver resection, but need to be developed. METHODS: Livers of male Lewis rats were subjected to 60, 90, or 120 minutes of normothermic ischemia. During a 120 minutes reperfusion period either GSH (50, 100 or 200 micromol/h/kg; n= 6-8) or saline (n= 8) was continuously administered via the jugular vein. RESULTS: Postischemic GSH treatment significantly prevented necrotic injury to hepatocytes as indicated by a 50-60% reduction of serum ALT and AST. After 1 hour of ischemia and 2 hours of reperfusion apoptotic hepatocytes were rare (0.50 +/- 0.10%; mean +/- SD) and not different in GSH-treated animals (0.65 +/- 0.20%). GSH (200 micromol GSH/h/kg) improved survival following 2 hours of ischemia (6 of 9 versus 3 of 9 rats; P < 0.05). Intravital fluorescence microscopy revealed a nearly complete restoration of sinusoidal blood flow. This was paralleled by a reduction of leukocyte adherence to sinusoids and postsinusoidal venules. Intravenous GSH administration resulted in a 10- to 40-fold increase of plasma GSH levels, whereas intracellular GSH contents were unaffected. Plasma concentrations of oxidized glutathione (GSSG) increased up to 5-fold in GSH-treated animals suggesting counteraction of the vascular oxidant stress produced by activated KC. CONCLUSIONS: Intravenous GSH administration during reperfusion of ischemic livers prevents reperfusion injury in rats. Because GSH is well tolerable also in man, this novel approach could be introduced to human liver surgery.     

Free Radical Scavenging Activity of Fullerenol on the Ischemia-reperfusion Intestine in Dogs

Fullerenol, a water-soluble C₆₀-fullerene derivative, has been demonstrated to have the capability to scavenge free radicals in vitro and in vivo. The purpose of this study was to investigate whether fullerenol can scavenge the free radicals that are massively induced during ischemia-reperfusion (I/R) injury of the small intestine, either preventively or therapeutically. Clamping the superior mesenteric artery and vein for 60 minutes to induce I/R injury was performed on male mongrel dogs. Thirty dogs were divided into three groups (10 in each): The control (C) group received no medication; the preventive (P) group received fullerenol (1 mg/kg) intravenously 30 minutes before ischemia; the therapeutic (T) group received the same dose of fullerenol immediately after reperfusion. This study was an experimental randomized trial. Intestinal segments were obtained 10, 20, 30, and 60 minutes after reperfusion; and blood samples and specimens of major organs were taken 60 minutes after reperfusion. Concentrations of lipid peroxidation products, including conjugated diene (CD) and malondialdehyde (MDA), and the level of glutathione (GSH) in intestinal tissue were determined. Serum indicators of liver and renal function were measured. Histologic examination of the small intestine and major organs were also performed. A significant increase in intestinal MDA and CD contents was detected at 30 and 60 minutes after reperfusion. The tissue GSH content, in contrast, was decreased 60 minutes after reperfusion. Administration of fullerenol diminished these changes both preventively and therapeutically. Liver and renal functions were within normal limits in all groups. Moreover no obvious histopathologic additional damage could be found in either the P or the T group. It is suggested that fullerenol can be considered a powerful scavenger for the free radicals induced by I/R injury of the small intestine.     

Gastric mucosal injury caused by hemorrhagic shock and reperfusion: protective role of the antioxidant glutathione

Oxygen free radicals have been implicated as mediators of gastric mucosal injury caused by ischemia/reperfusion. We investigated the role of exogenous and endogenous glutathione (reduced glutathione, GSH) in gastric mucosal injury associated with hemorrhagic shock and reperfusion. Mucosal GSH content was found to be consistently higher in the antrum than in the corpus. Ischemia (hemorrhage to 25 to 30 mm Hg) followed by retransfusion of shed blood, but not ischemia alone, caused a marked drop in gastric mucosal GSH and gross mucosal injury, which was confined to the corpus and spared the antrum. Chemical depletion of gastric mucosal GSH with diethylmaleate or inhibition of GSH synthesis with buthionine sulfoximine increased mucosal injury in the corpus and also rendered the antral mucosa susceptible to ischemia/reperfusion injury. Pretreatment with exogenous GSH provided marked protection against gross mucosal ischemia/reperfusion injury and prevented the ischemia/reperfusion-induced drop in mucosal GSH. These data suggest that the mucosal availability of the antioxidant GSH is an important protective factor against the development of gastric mucosal ischemia/reperfusion injury and supports a major role of oxygen radical release in the pathogenesis of gastric ischemia/reperfusion injury.     

Protective effect of erythropoietin on renal ischemia and reperfusion injury

BACKGROUND: Multiple protective effects of erythropoietin (EPO), such as antiapoptotic, antioxidant, angiogenic and neuroprotective effects, against ischemia have been demonstrated in cell culture and animal models. Genistein is also a potent tyrosine kinase inhibitor. The aims of the present study were to evaluate the effects of EPO on renal ischemia/reperfusion injury and to determine the role of the tyrosine kinase pathway on this process. METHODS: Sprague-Dawley rats were assigned to five groups: (i) sham (Group I); (ii) control with renal ischemia (right nephrectomy and clamping on the left renal pedicle for 45 min and reperfusion; Group II); (iii) EPO + ischemia (Group III); (iv) genistein (an inhibitor of tyrosine kinase) + ischemia (Group IV); and (v) EPO + genistein + ischemia (Group V). Recombinant human EPO (1000 IU/kg) and genistein (10 mg/kg) were given 2 hours before ischemia. Blood samples and the left kidney were obtained after 45 min of reperfusion from half of the rats and after 24 h from the other half. RESULTS: The blood urea nitrogen, creatinine, tumour necrosis factor-alpha (P < 0.05) and interleukin-2 (P < 0.01) levels, and renal tissue lipid peroxidation (P < 0.05) were significantly lower in Group III than in Group II at 45 min of reperfusion. Following 24 h of reperfusion, EPO decreased tissue peroxidation and histopathological injury, whereas genistein reversed it. The most prominent ischemic injury was observed in Group IV in which genistein was administered. There was no significant difference between Groups II and V. CONCLUSIONS: These results suggest that EPO is effective in attenuating renal ischemia/reperfusion injury, and this effect may be related to tyrosine kinase activity.     

大鼠小肠缺血再灌注后肾脏损伤

通过对２０只大鼠小肠缺血再灌注模型和肾组织中脂质过氧化物的测定,并结合病理改变,以探讨小肠缺血再灌注后肾损伤的病理机制。结果表明：大鼠小肠缺血再灌注后,血脂质过氧化物明显升高,同时关浆内脂质过氧物明显高于对照组。提示小肠缺血再灌注后肾组织细胞确有明显损伤,其中氧自由基对肾组织的破坏可能是肾脏病理生理改变的主要因素。     

Protective Effect of MESNA (2-Mercaptoethane Sulfonate) Against Hepatic Ischemia/Reperfusion Injury in Rats

Purpose Reoxygenation of ischemic tissue generates various reactive oxygen metabolites (ROMs), which have a deleterious effect on various cellular functions. We evaluated the possible protective effect of 2-mercaptoethane sulfonate (MESNA) on hepatic ischemia/reperfusion (I/R) injury.Methods Wistar albino rats were subjected to 45-min hepatic ischemia, followed by 60-min reperfusion. 2-Mercaptoethane sulfonate, 150 mg/kg, or saline was given intraperitoneally (i.p.) twice, 15 min before ischemia and immediately before reperfusioin. We measured serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels to assess liver function. Liver tissue samples were taken to measure the levels of malondialdehyde (MDA), an end-product of lipid peroxidation; glutathione (GSH), a key antioxidant; and myeloperoxidase (MPO) activity, as an indirect index of neutrophil infiltration. We also measured hepatic collagen content, as a fibrosis marker.Results Plasma ALT and AST levels were higher in the I/R group than in the control group, but this increase was significantly decreased by MESNA treatment. Hepatic GSH levels, which were significantly depressed by I/R, increased back to the control levels in the MESNA-treated I/R group. Increases in tissue MDA levels and MPO activity caused by I/R injury decreased back to the control levels after MESNA treatment. Similarly, the increased hepatic collagen content in the I/R group decreased to the level of the control group after MESNA treatment.Conclusion The fact that MESNA alleviated I/R-induced injury of the liver and improved hepatic structure and function suggests that its antioxidant and oxidant scavenging properties may be of therapeutic value in protecting the liver against oxidative injury caused by I/R.     

The effect of caffeic acid phenethyl ester on ischemia-reperfusion injury in comparison with alpha-tocopherol in rat kidneys

Oxygen-derived free radicals have been implicated in the pathogenesis of renal injury after ischemia-reperfusion. Caffeic acid phenethyl ester (CAPE), an active component of propolis extract, exhibits antioxidant and anti-inflammatory properties. To determine whether CAPE offers any advantage over α-tocopherol, we compared their effects on an in vivo model of renal ischemia-reperfusion injury in rats. CAPE at 10 μmol/kg or α-tocopherol at 10 mg/kg was administered intraperitoneally before reperfusion. Acute administration of CAPE suppressed ischemia-reperfusion induced renal lipid peroxidation and tissue injury more than α-tocopherol. CAPE may therefore offer a therapeutic advantage in acute injury settings. Received: 9 October 2000 / Accepted: 23 February 2001     

Protective effect of N-acetylcysteine on renal ischemia/reperfusion injury in the rat

BACKGROUND: Oxygen free radicals are important components involved in the pathophysiological tissue alterations observed during ischemia/reperfusion (I/R). METHODS: The protective effect of N-acetylcysteine (NAC) against the damage inflicted by reactive oxygen species during renal I/R was investigated in Wistar Albino rats using biochemical parameters. Animals were unilaterally nephrectomized, and subjected to 45 min of renal pedicle occlusion followed by lh of reperfusion. N-acetylcysteine (150 mg/kg, i.p.) 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. For biochemical analysis, the lipid peroxidation product malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and protein oxidation (PO) were tested. Serum creatinine and BUN concentrations were measured for the evaluation of renal function. RESULTS: I/R induced nephrotoxicity, as evidenced by increases in BUN and creatinine, was reversed by NAC. The decrease in GSH and increases in MDA, MPO and PO induced by I/R indicated that renal injury involves free radical formation. CONCLUSIONS: Since NAC reversed these oxidant responses, and protected rat renal proximal tubules from in vitro simulated reperfusion injury, it seems that NAC protects kidney tissue against oxidative damage.     

盐酸氟桂利嗪对再灌注损伤时鼠肝细胞线粒体的作用

目的 盐酸氟桂利嗪对大鼠肝脏缺血／再灌注香肝细胞线粒体的影响。方法：将Ｗｉｓｔａｒ大鼠随机分为三组,每组１２只。Ａ组为对照组,Ｂ组缺血／再灌注组组,Ｃ组为盐酸氟桂利嗪组。其中Ｂ,Ｃ两组均阻断肝门造成肝脏完全缺血３０分钟后再灌注９０分钟。测定各组动物血清中ＡＬＴ,ＬＤＨ含量,肝细胞线粒体脂质过氧化物（ＬＰＯ）含量、行超微结构的观察。结果 与Ａ组比较,Ｂ组血清ＡＬＴ,ＬＤＨ活性显著加（Ａ,Ｂ二组,ＡＬ     

Role of angiotensin and endothelin in testicular ischemia reperfusion injury

Objectives: To determine whether angiotensin and endothelin have any role in testicular ischemia reperfusion injury by investigating the effects of the angiotensin converting enzyme inhibitor enalapril, selective non‐peptide angiotensin‐II type I blocker losartan and dual endothelin receptor blocker bosentan. Methods: Rats were anesthetized with thiopental sodium (50 mg/kg i.p.) before the operation. The left testicular artery and vein of rats were occluded for 1 h; before the bilateral orchiectomy, the organ was allowed to reperfuse for 3 h or 24 h. Enalapril (20 mg/kg i.p.), losartan (30 mg/kg i.p.), bosentan (10 mg/kg i.p.) or vehicle (saline) were given 30 min before reperfusion. Malondialdehyde level was measured in testicular tissue after 3 h of reperfusion. Histological examination was carried out after 24 h of reperfusion. Results: Ischemia reperfusion caused a significant increase in malondialdehyde level of ipsilateral testis, and histopathological injury in both ipsilateral and contralateral testes. Enalapril, losartan and bosentan treatments prevented the ischemia reperfusion‐induced augmentation in malondialdehyde levels. Only bosentan treatment ameloriated ischemia reperfusion‐induced histopathological alterations. Conclusions: Endothelin might play a more important role in pathogenesis of testicular ischemia reperfusion injury when compared with angiotensin.     

The cytoprotective effects of verapamil and iloprost (ZK 36374) on ischemia/reperfusion injury of kidneys

We investigated the cytoprotective effects of verapamil, a Ca channel blocker, and of iloprost (ZK 36374), a stable prostacyclin analogue, on ischemia/reperfusion (I/R) injury in Wistar albino rat kidneys that were subjected to 60 min of warm ischemia and reperfusion. The groups included sham, ischemia-untreated (ISCH), verapamil-treated (VER), iloprost-treated (ILO), and verapamil + iloprost (VER+ILO)-treated rats. The 7-day survival of all the treated groups was better than that of the ISCH group. The creatinine concentration on the 3rd day was significantly lower in the VER+ILO group than in the ISCH group. Serum creatinine on day 3 was also low in the VER+ILO groups compared to the ISCH group, although the differences were not significant. The creatinine values on day 7 were significantly lower in the VER and ILO group than in the control, VER, or ILO groups. The malondialdehyde (MDA) concentrations of the kidney cortex tissue after reperfusion in all groups were higher than normal. The tissue-reduced glutathione (GSH) concentrations of the kidneys sampled immediately after reperfusion were significantly lower in the ISCH group than in all of the other treated groups. These results indicate that although verapamil and iloprost have independent cytoprotective effects on 60-min warm ischemia/reperfusion injury of rat kidneys, the protection afforded when both drugs are combined is synergistic. The mechanism of cytoprotection is not limited to the suppression of lipid peroxidation, and a nearly complete protection of reperfusion injury can be obtained by such an intervention.     

Protective role of dehydroascorbate in rat liver ischemia-reperfusion injury

BACKGROUND: Oxidative stress plays an important role in liver ischemia/reperfusion (I/R) injury. Thus, enhancing the liver antioxidant capacity could be a promising therapeutic strategy. Ascorbate (AA) is considered the perfect antioxidant, but its therapeutic efficacy is greatly limited by its slow achievement of high intracellular levels. This might be circumvented by administering dehydroascorbate (DHA), which presents a several-fold greater uptake than AA, and undergoes rapid intracellular reduction to AA. Thus, our aim was to assess the protective role of DHA in liver I/R injury. MATERIALS AND METHODS: Wistar rats (200-300 g bw) were pretreated iv with different doses of AA or DHA 20 min before liver ischemia, followed by 6 h reperfusion. Liver damage was assessed by biochemical and morphological indices. RESULTS: DHA pretreatment induced a rapid increase in liver ascorbate levels, significantly higher than findings for AA, without any significant reduction in glutathione levels. Liver damage during I/R in controls showed significant increases in serum transaminases and hepatic thiobarbituric acid reactive substances with alterations of liver morphology. DHA administration induced a clear, significant protection against I/R injury, whereas liver damage was only moderately prevented by AA. CONCLUSIONS: DHA might represent a simple, effective therapeutic option to prevent liver damage associated with ischemia/reperfusion.     

供体小肠缺血再灌注损伤中bcl-2基因mRNA表达水平的研究

目的探讨bcl-2基因对供体小肠缺血再灌注损伤的调控作用及机制。方法以大鼠模型模拟供体小肠热、冷缺血及再灌注损伤过程,采用逆转录-定量聚合酶链式反应（RT－Q－PCR）技术检测bcl-2基因mRNA转录水平。结果bcl-2基因mRNA转录水平在热缺血再灌注各组中无明显差异;冷缺血再灌注后24小时bcl-2基因mRNA转录水平明显降低。结论RT－Q－PCR是一种灵敏、准确、快速的检测mRNA转录水平的方法。热缺血再灌注损伤不引起bcl-2基因mRNA转录水平的改变;冷缺血再灌注24小时bcl-2基因mRNA转录水平明显降低并可促进细胞凋亡的发生。