Effect of resveratrol on oxidative stress enzymes in rats subjected to 70% partial hepatectomy

This experimental study investigated the antioxidant status of rats after resveratrol (R) treatment following 70% partial hepatectomy. Thirty Wistar albino rats (200 to 250 g) were divided among: groups A and B (n = 10 each) underwent laparotomy and 70% partial hepatectomy (PH). Whereas rats in group A received resveratrol 60 mg/d per nasogastric tube for 7 days before and 3 days after PH (PH + R), those in group B underwent PH only. Rats in group C (n = 10) were subjected to a sham operation. Significant increases in tissue levels of reduced glutathione (GSH) and decreased malondialdehyde (MDA) levels were observed in the PH group receiving R compared with those of the PH group (P < .001 for all). Comparison of these parameters with those of the sham group revealed significantly higher tissue levels of GSH and lower MDA levels among sham-operated compared with PH + R and PH groups (P < .001 for all). Concerning the NO levels, a trend to a slightly decrease was observed in the PH + R group (P < .06). Interleukin-6 levels showed significant decreases in both PH + R and PH groups (P < .001 and P < .05, respectively). The tissue GSH levels were slightly decreased in PH + R (P < .05), and decreased in the PH group compared with the controls (P = .002). We have suggested that patients undergoing living donor liver transplantation would likely benefit from prophylactic treatment with foods having resveratrol.     

Protective effects of resveratrol on spleen and ileum in rats subjected to ischemia-reperfusion

Resveratrol is as an antioxidant with free radical-scavenging activity and finds its clinical application in the prevention of postischemic tissue injury following solid organ transplantation. This study investigates the effect of Resveratrol on spleen and ileum tissues subjected to hepatic ischemia-reperfusion (I/R) in rats. Twenty-four rats were recruited in the study as follows: group A: I/R (n = 8), group B: I/R + Resveratrol (n = 8), and group C: sham operation (n = 8). After intraperitonealy pretreatment of eight rats with resveratrol (15 mg/kg/d) for 5 days, 16 rats were subjected to 45 minutes of hepatic ischemia followed by 30 minutes reperfusion period. Resveratrol was given 15 minutes prior to ischemia and just before the reperfusion in rats. After reperfusion period all rats were sacrificed. Spleen and ileum tissues were examined spectrophotometrically to measure malondialdehyde (MDA), glutathione (GSH), and total nitrite, nitrate as an end product of nitric oxide (NO) levels. Concerning the spleen, statistically significant decrease of GSH and increase of MDA and NO levels were found group A when compared to groups B and C (P = .040, P = .004, and P = .001 group A vs group B; P = .05, P = .003, and P = .001 group A vs group C, respectively). Parallel results were obtained in ileum. A statistically significant decrease in GSH and an increase in MDA and NO levels in group A in respect to group B and group C was obtained (P = .048, P = .034, and P = .001 group A vs group B; P = .004, P = .001, and P = .003 group A vs group C, respectively). The result of this study shows that resveratrol has a protective effect on spleen and ileal mitochondrial oxidative stress in rats subjected to I/R.     

The effect of partial unilateral ureteral obstruction release and allopurinol on the renal malondialdehyde and glutathione levels

PURPOSE: The aim of the present study was to evaluate whether relief of partial unilateral ureteral obstruction (PUUO) with or without antioxidant drug affect renal tissue malonedialdehyde (MDA) and glutathion (GSH) levels. MATERIALS AND METHODS: A total of 25 rats were used in this PUUO study. Partial unilateral ureteral obstruction was created by the burial of the upper one-third of the left ureter in the psoas muscle. The rats were sacrificed on 28th day following PUUO. Relief of the obstruction was performed twenty minutes before sacrifice by cutting the proximal ureter in reperfusion group. 50 mg/kg intraperitoneal allopurinol was administered 20 minutes before relief of obstruction in the antioxidant group. Renal tissue MDA and GSH levels were measured in both kidneys. RESULTS: At the end of the study 5, 7 and 7 rats could only be interpreted in sham, reperfusion and antioxidant groups, respectively. While the mean left and right renal MDA and GSH levels were statistically different from each other in reperfusion group (P < 0.001), there were no significant differences in the sham (P > 0.05) and antioxidant (P > 0.05) group. Both the mean sham group left and right renal tissue MDA or GSH levels were significantly different from reperfusion group, but only the mean sham group left renal tissue MDA and right renal tissue GSH levels were not statistically different from antioxidant group (P < 0.05). The mean left or right renal MDA and GSH tissue levels of the antioxidant group were statistically different from reperfusion group (P < 0.05) except for the right renal tissue GSH level (P > 0.05). CONCLUSION: Partial unilateral ureteral obstruction leads to oxidative injury by relief of obstruction in both kidneys. The antioxidant allopurinol has a beneficial effect on renal MDA and GSH levels in both kidneys.     

Pyrrolidine dithiocarbamate prevents 60 minutes of warm mesenteric ischemia/reperfusion injury in rats

BACKGROUND: Pyrrolidine dithiocarbamate (PDTC) is a low-molecular-weight thiol antioxidant and potent inhibitor of nuclear factor-kappaB (NF-kappaB) activation. It has been shown to attenuate harmful effects of ischemia/reperfusion (I/R) injury in many organs. In recent animal studies, destructive effects of reperfusion injury has been demonstrated. In this study, we aimed to investigate whether PDTC prevents harmful effects of superior mesenteric I/R injury in rats. METHODS: Wistar-albino rats were randomly allocated into the following 4 groups: (1) sham-operated group--these animals underwent laparotomy without I/R injury (group I, n = 12); (2) sham+PDTC group--identical to sham-operated rats except for the administration of PDTC (100 mg/kg intravenous bolus) 30 minutes prior to the commencement of the experimental period (group II, n = 12); (3) I/R group--these animals underwent laparotomy and 60 minutes of ischemia followed by 120 minutes of reperfusion (group III, n = 12); (4) PDTC-treated group (100 mg/kg, intravenously, before the I/R, group IV, n = 12). All animals were killed, and intestinal tissue samples were obtained for investigation of intestinal mucosal injury, myeloperoxidase (MPO) activity, malondialdehyde (MDA) levels, glutathione (GSH) levels, and intestinal edema. RESULTS: There was a statistically significant decrease in GSH levels, along with an increase in intestinal mucosal injury scores, MPO activity, MDA levels, and intestinal tissue wet-to-dry weight ratios in group III when compared to groups I, II, and IV (P < .05). However, PDTC treatment led to a statistically significant increase in GSH levels, along with a decrease in intestinal mucosal injury scores, MPO activity, MDA levels, and intestinal tissue wet-to-dry weight ratios in group IV (P < .05). CONCLUSIONS: This study showed that PDTC treatment significantly prevented the reperfusion injury caused by superior mesenteric I/R. Further clinical studies are needed to clarify whether PDTC may be a useful therapeutic agent to use in particular operations where the reperfusion injury occurs.     

Protection of preconditioning, postconditioning and combined therapy against hepatic ishemia/reperfusion injury

Objective： To study the protective effect of ischenlic preconditioning （I-pre） and ischemic postconditioning （I- post） against ischenlia/reperfusion （I/R） injury in rat＇ s liver. Methods： Using rat model of hepatic segmental I/R injury, rats were divided into 5 groups： Group A （sham group）, Group B （I/R injury）, Group C （I-pre group）, Group D （I-post group ） and Group E （combined treatment of I-pre and I-post ）. Serum alanine aminotransferase （ ALT ）, aspartate aminotransferase （ AST）, malondiaidehyde （ MDA ）, glutathione （ GSH ）, superoxide dismutase （ SOD ）, glutathione peroxidase （GSH-Px） and myeloperoxidase （MPO） in hepatic tissues were determined, respectively. In addition, 7 days＇survival of Groups B, C, D and E were evaluated. Results. Compared with Group B, Groups C, D and E exhibited significantly decreased ALT and AST release, minimized tissue injury, suppressed values of MDA and MPO, increased activities of SOD, GSH-Px and GSH （P〈0.05 ）, as well as improved animal survival. The differences among Groups C, D and E were not statistically significant. Conclusions： I-pre, I-post and combined therapy of I-pre and I-post have protective effect against hepatic I/R injury, which is correlated with its function of reducing the production of reactive oxygen species, maintaining the activities of antioxidant systems and suppressing neutrophils recruitment. No additive effect can be obtained in Group E.     

Protective effect of resveratrol against renal oxidative stress in cholestasis

BACKGROUND/AIMS: This experimental study was designed to evaluate histological changes of the kidney and renal tissue levels of malondialdehyde (MDA), reduced glutathione (GSH), and nitric oxide (NO) and the effect of resveratrol on these metabolites after bile duct ligation in rats. METHODS: Secondary biliary cirrhosis was induced by bile duct ligation for 28 days. Swiss albino rats were divided into three groups. Group 1: Sham (n=7), Group 2: Bile duct ligation (n=7), Group 3: Bile duct ligation plus resveratrol (n=7). Bile duct ligation (BDL) plus resveratrol group received 10 mgr/kg dose of resveratrol intraperitoneally daily throughout 28 days. Kidney tissues were harvested to determine the tissue levels of MDA, GSH, and NO activity. Liver and kidney tissues were removed for light microscopic evaluation. RESULTS: Cholestasis was determined by biochemical and pathologic examination. In the resveratrol-treated rats, levels of MDA were significantly lower than those of the BDL group (p < 0.04). The levels of GSH in the resveratrol-treated rats were significantly higher than those in the BDL group (p < 0.01). The levels of NO in the resveratrol group were significantly lower than those in the BDL group (p < 0.01). CONCLUSION: The present study demonstrates that intraperitoneal administration of resveratrol in bile duct ligated rats maintains antioxidant defenses and reduces kidney oxidative damage. This effect of resveratrol may be useful in the preservation of renal oxidative stress in cholestasis.     

The Evaluation of Protective Effects of FK-506 on Neural Ischemic-Reperfusion Injury: an Experimental Study

Abstract Objective: In this study, we aimed to delineate the mode of neuroprotective action of FK-506, and demonstrated that FK-506 could decrease oxidative stress and apoptotic cell death in an in vivo rat model of neural ischemia-reperfusion after hemorrhagic shock. Methods: Thirty rats were used as experimental subjects and divided into five equal groups. Group A rats (sham group, n = 6) were anesthetized and craniotomies were performed for collecting brain tissue samples. In group B ischemia-reperfusion (I/R + 1 h, n = 6), group C (I/R + 24 h, n = 6), group D (I/ R + 1 h FK-506, n = 6) and group E (I/R + 24 h FK-506, n = 6), systolic blood pressure of the rats decreased to 40–50% of the normal level via bleeding from the femoral vein. Thus, a hemorrhagic shock and ischemic neural tissue model was formed. The bloodwas retained and given to the remaining animals in groups B, C,Dand E via femoral vein for reperfusion 20 min after the procedure. In group D and E, 1 mg/kg FK-506 in 0.5 ml isotonic solution was administered to the rats 5 min before reperfusion. Group B and D rats were sacrificed after 1 h and group Cand E rats were sacrificed 24 h after reperfusion; the rats were sacrificed via bleeding associated with intracardiac puncture. Craniotomy was also performed in groups B, C, D and E and brain tissue samples were fixed using neutral buffered 10% formaldehyde solution for immunohistopathological examination as in group A. Brain tissue superoxide dismutase (SOD) activities, malondialdehyde (MDA) levels, tissue myeloperoxydase (MPO) activities and apoptotic cell analyses with Apo 2.7 immunohistochemically were also performed in all groups. Results: The result of the study revealed that the SOD activities were lower for groups B (I/R + 1 h) and C (I/ R + 24 h) than for group A (sham group) (p < 0.05). In addition, SOD activities were higher in groups D (I/ R + 1 h FK-506) and E (I/R + 24 h FK-506) than in groups B (I/R + 1 h) and C (I/R + 24 h) (p < 0.05). MDA levels, MPO activities and the number of apoptotic cells were lower in group A (sham group) than in groups B (I/R + 1 h) and C (I/R + 24 h) (p < 0.05). In addition to these MDA levels, MPO activities and the number of apoptotic cells were higher in groups B (I/R + 1 h) and C (I/R + 24 h) as compared to groups D (I/R + 1 h FK-506) and E (I/R + 24 h FK-506) (p < 0.05). Conclusion: The results suggest that the prophylactic use of FK-506 in an in situ ischemic neural tissue may prevent reperfusion injury.     

The effect of N-acetylcysteine on pulmonary lipid peroxidation and tissue damage

BACKGROUND: We aimed to investigate the effect of N-acetylcysteine (NAC) on pulmonary lipid peroxidation and tissue damage in experimental obstructive jaundice (OJ) stimulated by lipopolysaccharide (LPS) in this study. MATERIALS AND METHODS: We randomized 40 rats into five groups. Group A: Sham (n = 8); group B: OJ (n = 8); group C: OJ + lipopolysaccharide (LPS; n = 8); group D: OJ + NAC + LPS (n = 8); group E: OJ + LPS + NAC (n = 8). OJ was performed by common bile duct ligation and division in all groups except the sham group. At the fifth day, the rats were jaundiced. At the fifth day of OJ, LPS was injected 10 mg/kg intraperitoneally to the rats and at the tenth day, the rats were sacrificed in group C. In group D; at the fifth day of OJ, NAC was started 100 mg/kg subcutaneously and the same dose NAC injection repeated every day for 5 days. At the tenth day of OJ, LPS was injected 10 mg/kg intraperitoneally to the rats and then after 6 h they were sacrificed. In group E; 10 mg/kg LPS was administered intraperitoneally at fifth day of OJ and after then NAC was started 100 mg/kg subcutaneously and the same dose NAC injection repeated every day for 5 days and at the tenth day, the rats were sacrificed. Tissue samples were harvested through a midline incision, and lungs were resected and examined histopathologically and immunohistochemically for tissue damage scoring. The blood was taken by cardiac puncture and malondialdehyde (MDA), myeloperoxidase (MPO), and levels of total antioxidant status were detected with biochemical methods to evaluate lung tissue damage. RESULTS: Increase in lung and serum MDA and MPO levels, as well as decrease in total antioxidant status, were observed in groups B and C when compared with the sham group (P = 0.0001, for each comparison). Furthermore, the lung tissue damage was observed in the same groups by histopathological examination when compared with sham group. There was significant decrease at serum and lung MPO and MDA levels after the NAC application in groups D and E, when compared with group C (P = 0.0001, for each comparison). Antioxidant status in groups D and E were increased in the presence of NAC (P = 0.0001, for each comparison). Lung histology was prevented relatively in group D when compared with groups B and C. CONCLUSION: Results of the study indicate that NAC has protective effect on pulmonary lipid peroxidation and tissue damage before and after LPS administration.     

Pretreatment with Pentoxifylline and N-Acetylcysteine in Liver Ischemia Reperfusion-Induced Renal Injury

Background and Aims: Acute hepatic injury causes systematic inflammatory responses which may finally lead to functional disturbances in remote organs. In this study, the effects of an inhibitor of inflammatory cytokines (pentoxifylline, PTX) and a well-known antioxidant, N-acetylcysteine (NAC), were evaluated on renal damage and oxidative stress following liver ischemia reperfusion (IR). Method: Five groups of six male rats were used. Group 1 was sham operated. In group 2, 90 min liver partial ischemia was induced by a clamp around both hepatic artery and portal vein and then followed by 4 h of reperfusion. In groups 3 and 4, PTX or NAC was injected intraperitoneally before the ischemia, while in group 5 both drugs were co-administered. The levels of alanine amino-transferase (ALT), aspartate amino-transferase (AST), blood urea nitrogen (BUN), and creatinine in serum as well as malonyldialdehyde (MDA) and glutathione (GSH) levels and morphological changes in renal tissues were assessed. Results: Significant increase in the serum levels of ALT and AST in IR group is indicative of liver functional damages. Elevated BUN and renal tissue MDA, decreased GSH levels, and morphological damages in IR group demonstrate a significant kidney injury and oxidative stress comparing to sham group. Administration of PTX alone and PTX + NAC prevented the IR-induced increase in renal MDA levels. Administration of both drugs and their co-administration prevented the reduction in renal GSH levels and morphological changes. Conclusion: Pretreatment with PTX and NAC before liver IR may be useful to ameliorate renal oxidative damage by preservation of cellular GSH concentration and a reduction in MDA levels.     

Effect of resveratrol and melatonin on oxidative stress enzymes, regeneration, and hepatocyte ultrastructure in rats subjected to 70% partial hepatectomy

AIM: We sought to compare the antioxidant effects of resveratrol (R) and melatonin (M) after 70% partial hepatectomy (PH) as evidenced by ultrastructural alterations and effects on hepatocyte proliferation and apoptosis. METHODS: Twenty-six male Wistar albino rats were randomized into four groups: group A (n = 8) resveratrol (R); group B (n = 8) melatonin (M); group C (n = 5) control PH; group D (n = 5) sham operated animals. The rats that received either R or M were sacrificed a week after PH. The malondialdehyde, glutathione, glutathione S-transferase, and nitric oxide levels were estimated in liver homogenates. The morphological changes were investigated using light and electron microscopy (EM). Cell proliferation was detected by immunohistochemical staining with monoclonal antibodies to Ki-67. Apoptosis was detected by the transferase-mediated dUTP nick end-labeling method. RESULTS: PH induced hepatic LP, decreased GSH and NO, and inhibited GST activity (P < .05). R and M completely prevented PH-induced lipid peroxidation, decreased hepatic GSH and NO levels (P < .05). The inhibition of GST activity was prevented by R (P < .05), but not with M (P > .05). In the PH group EM showed severe morphological changes: mitochondrial degeneration, vacuoles, lipid droplets, and myelin-like figures. In both the R and M groups, morphological alterations repaired protective effects more prominently in the R group. Ki-67 indices (KI) were increased in the PH group and decreased in both R and M groups (P < .001). In the M group, KI was the lowest, but the difference compared with R was not significant (P > .05). Apoptosis was slightly increased in PH, but in either the R or M groups, apoptosis was intensively increased (P < .001). Increased apoptosis was greatest in the M group and the difference compared with the R group was statistically significant (P < .05). CONCLUSION: R and M suppressed PH-induced oxidative damage, attenuated proliferation, and stimulated apoptosis. When we compared R and M, R showed more potent antioxidative effects and was morphologically more protective to hepatocytes. Antiproliferative effects of M were more potent. Because of their potent antioxidative effects, R and M can be effective for oxidative damage like ischemia-reperfusion injury; however, because of the adverse effects on proliferation and apoptosis more studies are needed in states in which regeneration is critical.     

The role of melatonin in prevention of intestinal ischemia-reperfusion injury in rats

BACKGROUND/PURPOSE: The aim of this study was to determine the effect of melatonin, a hormone that is known as an antioxidant, on the prevention of tissue damage during mesenteric ischemia/reperfusion (I/R). METHODS: A total of 40 young Wistar-albino rats were divided equally into 4 groups with varied treatment. Group 1 was control (sham), group 2 was I/R, group 3 was I/R plus melatonin (10 mg/kg) and group 4 was I/R plus melatonin (20 mg/kg). I/R was realized as follows: after laparatomy, a microvascular atraumatic clip was placed across the superior mesenteric artery (SMA) under general anaesthesia, and it was removed after ischemia for 30 minutes. The first dose of melatonin was applied intraperitoneally at the start of reperfusion. The second and third doses were applied intramuscularly on the first and second day. Only SMA dissection under general anaesthesia was carried out in the control group rats. On the third day of the study all the rats were killed, and their bowels were removed. Malondialdehyde (MDA) levels were assayed as an index of lipid peroxidation reflecting free radical reaction in the intestine. Histopathologic analysis was made using light microscopy in a blind fashion. RESULTS: The levels of tissue MDA were found to be significantly lower in groups 3 and 4 compared with group 2 (P < .05). The MDA levels of group 4 did not differ significantly from that of the control group (P > .05). The histopathologic results were consistent with the MDA levels. CONCLUSION: These results suggest that melatonin has a strong antioxidant effect in preventing intestinal I/R damage, and that this effect is exerted in a dose-dependent manner.     

抗氧化剂对去卵巢大鼠骨生物力学和血清生化指标的影响

目的 研究抗氧化剂VitC、VitE及还原璎谷光甘肽(GSH)不同配伍用药方法 对去卵巢骨质疏松症大鼠骨生物力学及血清生化指标的影响,探讨抗氧化剂不同方案对去卵巢大鼠骨质疏松症的治疗作用.方法 4个月龄雌性SD大鼠70只,随机取50只行双侧卵巢切除术,20只行假手术.3个月后随机从手术组和假手术组各取10只大鼠检测体质量、子宫湿蕈、左侧股骨及腰椎骨密度、生物力学特性和血清生化指标Ca<'2+>、肌肝(Cr)、碱性磷酸酶(ALP)水平,以确定骨质疏松模型建立成功.确定模型建立成功后,其余动物分为A(假手术)、B(去卵巢生理盐水对照组,OVX control)、C(VitC+VitE)、D(GSH)、E(VitC+VitE+GSH)五组,每组10只.VitC[750 mg/(kg·d)]、GSH[125 mg/(kg·d)]腹腔注射,VitE[250 mg/(kg·d)]灌胃,模型组每天以生理盐水腹腔注射.3个月后,检测各组动物左侧股骨及第5腰椎生物力学特性和血清生化指标. 结果 检测骨质疏松模型实验中,模型组动物同假手术组相比,体质量明显增加,子宫萎缩,子宫湿重显著降低,左侧股骨及腰椎骨密度明显降低,左侧股骨生物力学最大载荷显著降低,血清Ca<'2+>、ALP、Cr水平升高.抗氧化剂治疗3个月后,与模型组相比,治疗组D、E组左侧股骨最大载荷、弹性载荷以及第5腰椎最大载荷均明显增加;血清ALP各组均显著降低;超氧化物歧化酶(SOD)、谷光苷肽过氧化物酶(GSH-Px)水平和血清抑制OH<'->能力D、E组显著升高;丙二醛水平C、D组显著降低;各组血清Ca<'2+>水平无明显改变. 结论 抗氧化刺崩药组合GSH和GSH+VitC+VitE能明显改善骨生物力学最大载荷和弹性载荷及血清抗氧化指标抑制OH<'->能力、SOD和GSH-Px,对骨质疏松具有较显著改善作用.     

Can preconditioning reduce laparoscopy-induced tissue injury?

Background: Pneumoperitoneum (P) created to facilitate laparoscopy (L) is associated with splanchnic perfusion, ischemia/reperfusion (I/R) injury, and oxidative stress. In this randomized controlled experimental study with blind outcome assessment, we evaluated the effect of preconditioning (PRE) on L-induced I/R injury. Methods: The subjects were 40 Sprague-Dawley male rats. P was created in all except controls, using carbondioxide (CO₂) insufflation under a pressure of 15 mmHg. PRE consisted of 10 min of P, followed by 10 min of deflation (D). The rats were randomized to the following groups: Group P was subjected to 60 min of P. Group P/D was subjected to 60 min of P, followed by 45 min of D. Group PRE/P was subjected to PRE, followed by 60 min of P. Group PRE/P/D was subjected to PRE, followed by 60 min of P and 45 min of D. Group C (control) was subjected to a sham operation, without P. Its anesthesia time was equal to that for group PRE/P/D. At the end of the experiments, the rats were killed; blood, liver, and kidney samples were then obtained and coded. Plasma alanine aminotransferase (ALT) and malondialdehyde (MDA), as well as homogenized tissue MDA levels and glutathione (GSH) activities, were measured; tissue samples were assessed for histopathological evidence of injury; all assessments were done by investigators blinded to the study design. The results were decoded and analyzed statistically with the Kruskal-Wallis and Mann Whitney tests. A p < 0.05 was considered significant. Results: Plasma ALT as well as plasma, liver, and kidney MDA levels and liver and kidney injury scores were increased, whereas liver and kidney GSH values were decreased in groups P and P/D, as compared to group C. Rats subjected to PRE before P had plasma ALT, kidney MDA, and kidney and liver GSH levels comparable to controls; their kidney and liver injury scores were higher than controls but significantly lower than nonpreconditioned animals. PRE enabled decreased plasma, kidney, and liver MDA as well as increased kidney GSH if applied before P; its efficacy on oxidative stress was limited to providing decreased kidney MDA and increased kidney GSH if applied before P/D. However, PRE significantly attenuated kidney and liver injury after P as well as P/D. Conclusion: PRE consisting of 10 min of P followed by 10 min of D decreases the oxidative stress induced by sustained P in the plasma, liver, and kidney. PRE significantly limits liver and kidney injury after prolonged P and P/D. After further studies to define its ideal timing, PRE before L incorporating P may have clinical relevance, especially for elderly patients or those with impaired hepatic and/or renal function or perfusion. Presented in poster format at the 10th International Congress of the European Association for Endoscopic Surgery (E.A.E.S.), Libson, Portugal, 2–5 June 2002     

铁死亡在肝缺血—再灌注损伤大鼠肠损伤中的作用

目的 探究铁死亡在肝缺血-再灌注损伤(HIR)大鼠肠损伤中的作用。方法 选择健康清洁级雄性SD大鼠40只,周龄8～10周,体重220～260 g。采用随机数字表法将大鼠分成四组：假手术组(S组)、铁死亡抑制剂Ferrostatin-1+假手术组(SF组)、HIR模型组(IR组)和铁死亡抑制剂Ferrostatin-1+HIR模型组(IF组),每组10只。S组腹腔注射等容量0.02%DMSO,30 min后行假手术,仅进行开腹、分离第一肝门和关腹处理。SF组腹腔注射Ferrostatin-1(溶于0.02%DMSO)5 mg/kg, 30 min后行假手术。IR组腹腔注射等容量0.02%DMSO,30 min后制备HIR模型。IF组腹腔注射Ferrostatin-1(溶于0.02%DMSO)5 mg/kg, 30 min后制备HIR模型。于再灌注后8 h处死大鼠,取小肠组织,采用ELISA法检测肠组织丙二醛(MDA)、谷胱甘肽(GSH)和铁(Fe²⁺)浓度;采用速率法检测血清中ALT和AST活性;采用Western blot法检测谷胱甘肽过氧化物酶4(GPX4)、铁...     

Lycopene has reduced renal damage histopathologically and biochemically in experimental renal ischemia-reperfusion injury

Abstract

Background: The present study aimed to investigate whether the inflammatory and antioxidant lycopene has a therapeutic effect against renal ischemia/reperfusion (I/R) injury. Materials and methods: In this study, 24 Wistar-Albino rats, weighing from 200 to 250?g, were divided into four groups. All rats underwent median laparotomy under anesthesia. No procedures were performed in the control group (Group C), whereas 100?mg/kg lycopene was administered by gavage in the lycopene group (Group L). The arteries of both kidneys were clamped for 45?min in the ischemia group (Group I), whereas 100?mg/kg lycopene was administered by gavage 30?min before clamping renal arteries, and ischemia was performed in the treatment group (Group T) rats. For all rats, blood samples and renal tissues were collected at 6?h of reperfusion. Samples were used to examine serum BUN, creatinine, MDA and GSH levels, and the renal tissues were used to examine MDA and GSH levels, and renal histopathologies. Results: The treatment group had statistically significant lower serum MDA levels, histopathological tubular vacuolization, loss of brush border and tubular dilatation (p?<?0.05), whereas serum BUN, creatinine, tissue MDA, and tissue and serum GSH levels were improved in favor of the treatment group, even though it was not statistically significant (p?>?0.05). Conclusion: The present study demonstrated that lycopene, which was administered prior to renal I/R injury, prevented renal damage through biochemical and histopathological parameters.     

Effect of Leptin and Apelin Preconditioning on Hepatic Ischemia Reperfusion Injury in Rats

Leptin and apelin are important adipocytokines involved in a variety of endocrine and paracrine functions. The aim of this study was to evaluate the effect of exogenous leptin and apelin preconditioning on hepatic ischemia reperfusion (I/R) injury in rats. Forty mice were assigned to four groups (n = 10): sham-operated control (sham), I/R injury, I/R + leptin (I/R + L), and I/R + apelin (I/R + A). Leptin 100 μg/kg/day and apelin 2 μg/kg/day were delivered intraperitoneally starting 3 days prior to surgical procedure in I/R + L and I/R + A groups, respectively. All I/R groups underwent 45 min of warm ischemia, followed by 30 min of reperfusion. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), liver malondialdehyde (MDA) and glutathione (GSH), and liver histopathology were compared between groups. MDA was elevated in I/R, but stayed similar in I/R + L and I/R + A compared to sham. I/R + A had significantly lower MDA compared to I/R. GSH levels did not differ significantly between the groups. ALT and AST were elevated in all I/R groups, but significant reduction was observed in I/R + L and I/R + A compared to I/R. Liver histopathology was mostly mild in I/R + L and I/R + A, in contrast to severe injury observed in the I/R group. Leptin and apelin preconditioning significantly reduced hepatic I/R injury in rats.     

右美托咪啶对脓毒症大鼠血清炎性因子和氧化应激反应的影响

目的 探讨右美托咪啶对脓毒症大鼠血清炎性因子和氧化应激反应的影响.方法 健康雄性SD大鼠30只,10～ 14周龄,体重250～300 g,采用随机数字表法,将其随机分为3组(n=10):假手术组(S组)、脓毒症组(CLP组)和脓毒症+右美托咪啶组(CLP+D组).CLP组和CLP+D组采用盲肠结扎穿孔术制备脓毒症模型,CLP+D组术毕静脉输注右美托咪啶10 μg·kg-1·h-1至大鼠死亡或术后12 h,S组和CLP组给予等容量生理盐水1ml·kg-1·h-1.每组取5只大鼠,分别于术前(基础状态)、术后1、6、12 h时采集股动脉血样,测定血清IL-6、IL-10、SOD及MDA的水平.记录术后12 h内大鼠生存情况.结果 与S组比较,CLP组术后1、6、12 h时血清IL-6、IL-10和MDA的浓度升高,血清SOD活性和生存率降低(P＜0.05);与CLP组比较,CLP+D组术后6、12 h时血清IL-6和MDA的浓度降低,术后12 h时血清SOD活性和生存率升高(P＜0.05).结论 右美托咪啶可以提高脓毒症大鼠的生存率,其机制与抑制炎性因子释放及氧化应激反应有关.     

Effects of carbon dioxide pneumoretroperitoneum on free radical formation in remote organs and use of verapamil as an antioxidant

BACKGROUND AND PURPOSE: Pneumoretroperitoneum (Prp) acts as an ischemia/reperfusion (I/R) model. Ischemia/reperfusion (I/R) injury causes production of reactive oxygen species, which affect organs remote from the sites of I/R. The aim of this study was to assess the remote organ changes after Prp and to explore the effects of antioxidants. MATERIALS AND METHODS: Eighteen adult rabbits were randomized to three groups, each consisting of six rabbits. Group I (control) underwent balloon dissection of the left retroperitoneal space without gas insufflation. In group II (Prp), carbon dioxide at 10 mm Hg was applied for 2 hours after the balloon dissection (ischemia period) and for 1 hour after desufflation (reperfusion period). In group III (Prp + antioxidant), 5 minutes before the experiment, verapamil at 0.2 mg/kg was given intravenously and the same procedure was employed as in group II. Hepatic, pulmonary, opposite kidney, and treated kidney malondialdehyde (MDA) and reduced glutathione (GSH) levels were evaluated to show response to Prp. RESULTS: Pneumoretroperitoneum exerted oxidative stress on all tissues with an increase of MDA (P < 0.05) and a decrease of GSH (P < 0.05). The verapamil-treated group showed lower values of MDA (P < 0.05) and higher values of GSH (P < 0.05) than group II. CONCLUSION: Pneumoretroperitoneum increased oxidative stress in all remote organs tested. Verapamil reduced the oxidative stress. We concluded that Prp should be employed carefully in patients with limited vital organ capacity. Verapamil administration may be considered for protection against tissue injury attributable to oxidative stress in these patients.     

Beneficial effects montelukast,cysteinyl-leukotriene receptor antagonist,on renal damage after unilateral ureteral obstruction in rats

Introductıon

Ureteral obstruction is a common pathology and caused kidney fibrosis and dysfunction at late period. In this present, we investigated the antifibrotic and antiinflammatory effects of montelukast which is cysteinyl leukotriene receptor antagonist, on kidney damage after unilateral ureteral obstruction(UUO) in rats.

Mateirıals and Methods

32 rats divided four groups. Group 1 was control, group 2 was sham, group 3 was rats with UUO and group 4 was rats with UUO which were given montelukast sodium (oral 10 mg/kg/day). After 14 days, rats were killed and their kidneys were taken and blood analysis was performed. Tubular necrosis, mononuclear cell infiltration and interstitial fibrosis scoring were determined histopathologically in a part of kidneys; nitric oxide(NO), malondialdehyde(MDA) and reduced glutathione(GSH) levels were determined in the other part of kidneys. Urea-creatinine levels were investigated at blood analysis. Statistical analyses were made by the Chi-square test and one-way analysis of variance (ANOVA).

Results

There was no difference significantly for urea-creatinine levels between groups. Pathologically, there was serious tubular necrosis and fibrosis in group 3 and there was significantly decreasing for tubular necrosis and fibrosis in group 4(p<0.005). Also, there was significantly increasing for NO and MDA levels; decreasing for GSH levels in group 3 compared the other groups(p<0.005).

Conclusıon

We can say that montelukast prevent kidney damage with antioxidant effect, independently of NO.     

Effect of fish oil, olive oil, and vitamin E on liver pathology, cell proliferation, and antioxidant defense system in rats subjected to partial hepatectomy

The high capacity of liver regeneration after partial hepatectomy (PH) is well known. This study investigated the role of the antioxidant defense system in regeneration among Wistar-albino male rats subjected to 70% partial hepatectomy after a pretreatment period of 2 weeks with eicosapentanoic acid (EPA) rich fish oil (FO), first pressed virgin olive oil (OO), or vitamin E. The control group of 10 rats underwent PH only. On postoperative day 3, all rats were humanely killed. Liver sections of animals treated with FO or vitamin E showed significant increases in regeneration within both liver parenchyma and cut surface compared with the control group (P < .05). Liver sections of OO displayed an insignificant increase in liver regeneration (P > .05), with less increase in parenchyma than of the cut surface. The enhancement of the liver parenchymal regeneration in the FO group was significantly greater than that of the vitamin E group. Concerning liver function tests (LFT), there was no significant difference among the groups. When the treatment groups were compared to the control group glutathione (GSH) levels were increased and content of malondialdehyde (MDA), nitric oxide (NO), and superoxide dismutase (SOD) were decreased. Based on these results, we concluded that after 70% PH in rats, the liver parenchyma and cut surface regeneration were greatest with FO and least with OO treatment. Both FO and vitamin E served to improve the antioxidant defense system more than OO treatment.