己酮可可碱在肺缺血-再灌注损伤中的作用

目的　探讨己酮可可碱 (PTX)对肺缺血 -再灌注损伤的保护作用。　方法　 72只大鼠随机分为 3组 ,每组 2 4只。 组 :未行缺血及再灌注处理 ; 组 :行左肺缺血和再灌注处理 ; 组 :行左肺缺血和再灌注处理 ,并给予己酮可可碱。采用在体肺温缺血 -再灌注损伤的模型 ,于缺血 45分钟、再灌注 1小时、2小时和 4小时进行动脉血气分析、肺组织含水量、支气管肺泡灌洗液白蛋白含量、血浆和左肺组织丙二醛、左肺组织和支气管肺泡灌洗液髓过氧化物酶(MPO)活性测定。　结果　 组再灌注 2小时和 4小时动脉血氧分压显著降低 ,各时间点左肺含水量、支气管肺泡灌洗液白蛋白含量、血浆丙二醛、左肺组织、支气管肺泡灌洗液中髓过氧化物酶均显著升高 ,PTX可改善上述指标变化。结论　 PTX通过抑制中性粒细胞肺内聚集 ,减轻肺血管内皮细胞损伤程度 ,而防止损伤的发展     

Ameliorative Effects of Proanthocyanidin on Renal Ischemia/Reperfusion Injury

Introduction. Several natural products have been reported to have beneficial effects on ischemia/reperfusion (I/R) injury, particularly from a preventative perspective. Therefore, this study was designed to investigate the efficiency of proanthocyanidin (PA), a natural product derived from grape seed, on renal dysfunction and injury induced by I/R of rat kidney. Materials and Methods. Twenty-four male Sprague-Dawley rats were divided into three groups: sham-operated, I/R, I/R+PA. Rats were given PA (100 mg/kg/day peroral) 7 days prior to I/R. All rats except sham-operated underwent 60 min of bilateral renal ischemia followed by 6 h of reperfusion. After reperfusion, kidneys and blood were obtained for evaluation. Superoxide dismutase, glutathione peroxidase, malondialdehyde, protein carbonyl content, and nitrite/nitrate level (NO_x) were determined in the renal tissue. Serum creatinine (S_Cr), blood urea nitrogen (BUN), and aspartate aminotransferase (AST) were determined in the blood. Additionally, renal sections were used for histological grade of renal injury. Results. PA significantly reduced the I/R-induced increases in S_Cr, BUN, and AST. In addition, PA markedly reduced elevated oxidative stress product, restored decreased antioxidant enzymes, and attenuated histological alterations. Moreover, PA attenuated the tissue NO_x, levels indicating reduced NO production. Conclusions. The pretreatment of rats with PA reduced the renal dysfunction and morphological changes, ameliorated cellular injury, and restored renal antioxidant enzymes caused by renal I/R.     

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.     

Caffeic Acid Phenethyl Ester Alleviates Mesenteric Ischemia/Reperfusion Injury

ABSTRACT

Purpose: We aimed to investigate the effects of caffeic acid phenethyl ester (CAPE) on intestinal mucosal injury induced by superior mesenteric occlusion. Methods: This experimental study was conducted on 48 male Wistar-albino rats. The animals were randomly allocated into four groups: (i) Sham-operated group, laparotomy without intestinal ischemia/reperfusion (IR) injury (n = 12); (ii) Sham + CAPE group, identical to group 1 except for CAPE treatment (10 μmol/kg, intravenously) (n = 12); (iii) Intestinal IR group, 60 min of superior mesenteric ischemia followed by 3 hr of reperfusion (n = 12); and (iv) (IR + CAPE)-treated group, 10 μmol/kg injection of CAPE intravenously 30 min before the reperfusion period (n = 12). We evaluated the degree of intestinal mucosal injury on a grading scale, histopathologically, and by measuring oxidative stress markers and antioxidant parameters, biochemically. Intestinal edema was estimated by using wet/dry weight ratios. The plasma proinflammatory cytokine levels were measured. Animal survival was observed up to one week. Results: Intestinal mucosal injury scores were significantly decreased with CAPE administration (p < .05). CAPE treatment significantly reduced oxidative stress markers in the intestinal tissues (p < .05) and the plasma proinflammatory cytokine levels (p < .05), and significantly increased antioxidant parameters in the intestinal tissues (p < .05). Intestinal edema was significantly alleviated by CAPE treatment (p < .05). The survival rates of CAPE-treated IR animals were significantly higher than IR-subjected rats (p < .05). Conclusion: This study clearly showed that CAPE treatment significantly alleviated the intestinal mucosal injury caused by superior mesenteric ischemia/reperfusion. Further clinical studies are required to clarify whether CAPE has a useful role in reperfusion injury during particular surgeries in which IR-induced organ injury occurs.     

Beneficial Effects of N-Acetylcysteine and Ebselen on Renal Ischemia/Reperfusion Injury

Abstract

Introduction: It has been demonstrated that peroxynitrite accompanies acute renal ischemia and contributes to the pathophysiology of renal damage. Therefore, we aimed to investigate the roles of N-acetylcysteine (NAC), a well-known powerful antioxidant, and ebselen (E), a scavenger of peroxynitrite, on renal injury induced by renal ischemia/reperfusion injury (IRI) of rat kidney. Materials and methods: Forty male Sprague–Dawley rats were divided into five groups: sham, renal IRI, renal IRI+NAC, renal IRI+E, and renal IRI+NAC+E. IR injury was induced by 60 min of bilateral renal ischemia followed by 6 h of reperfusion. After reperfusion, kidneys and blood samples were obtained for histopathological and biochemical evaluations. Results: Renal IR resulted in increased malondialdehyde and nitrite/nitrate levels suggesting increased lipid peroxidation and peroxynitrite production and decreased superoxide dismutase and glutathione peroxidase activities. Both NAC and E alone significantly decreased malondialdehyde and nitrite/nitrate levels and increased superoxide dismutase and glutathione peroxidase activities. Additionally in the renal IRI+NAC+E group, all biochemical results were quite close to those of sham group. Histopathologically, the kidney injury in rats treated with combination of NAC and E was found significantly less than the other groups. Conclusions: Both NAC and E are able to ameliorate IRI of the kidney by decreasing oxidative and nitrosative stresses and increasing free radical scavenger properties. Additionally, combination of NAC and E prevents kidney damage more than when each drug is used alone, suggesting that scavenging peroxynitrite nearby antioxidant activity is important in preventing renal IRI.     

The Effect of Dietary Ginger (Zingiber officinals Rosc) on Renal Ischemia/Reperfusion Injury in Rat Kidneys

Oxidative stress has been considered as one of the possible mechanisms of ischemia/ reperfusion (I/R) injury in the kidney. The aim of this study was to analyze the possible protective effect of dietary ginger (Zingiber officinals Rosc), a free radical scavenger, on renal I/R injury in rats. The protective effect of ginger against the damage inflicted by reactive oxygen species (ROS) during renal I/R was investigated in Wistar albino rats using histopathological and biochemical parameters. Thirty rats were randomly divided into five experimental groups (i.e., control, sham-operated, ginger, I/R, and I/R + ginger groups, n = 6 each). The ginger and I/R + ginger groups were fed on the test diet containing 5% ginger. The rats were subjected to bilateral renal ischemia followed by reperfusion in I/R and I/R + ginger groups. At the end of the reperfusion period, rats were sacrificed, and kidney function tests, serum and tissue oxidants and antioxidants, and renal morphology were evaluated. Serum urea, creatinine, and cystatin C (CYC) levels were significantly elevated in the ischemia group, but these levels remained unchanged in the ginger + I/R group compared to the I/R group. Reduction of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) enzyme activity was significantly improved by the treatment with ginger compared to I/R group. Administration of ginger resulted in significant reduction levels of tissue malondialdehyde (MDA), NO, protein carbonyl contents (PCC) in the ginger + I/R group compared with the I/R group. Ginger supplementation in the diet before I/R injury resulted in higher total antioxidant capacity (TAC) and lower total oxidant status (TOS) levels than I/R group. The ginger supplemented diet prior to I/R process demonstrated marked reduction of the histological features of renal injury. The findings imply that ROS play a causal role in I/R-induced renal injury, and ginger exerts renoprotective effects probably by the radical scavenging and antioxidant activities.     

The Effects of Medical Ozone Therapy on Renal Ischemia/Reperfusion Injury

Introduction: This study was designed to investigate the possible beneficial effects of medical ozone therapy (OT), known as an immunomodulator and antioxidant, on the renal function, morphology, and biochemical parameters of oxidative stress in kidneys subjected to ischemia/reperfusion injury (IRI). Materials and methods: Thirty male Sprague–Dawley rats were classified into three groups: control, renal IRI, and renal IRI + OT. The IRI group was induced by bilateral renal ischemia for 60 min, followed by reperfusion for 6 h. After reperfusion, the kidneys and blood of rats were obtained for histopathologic and biochemical evaluation. Results: Renal IRI increased the tissue oxidative stress parameters (lipid peroxidation, protein oxidation, and nitrite plus nitrate) and decreased the antioxidant enzyme activities (superoxide dismutase and glutathione peroxidase). The serum neopterin levels showed correlation with oxidative stress parameters. All these parameters were brought to control values in the treatment group. Histopathologically, the kidney injury in the treatment group was significantly lesser than in the renal IRI group. Conclusions: Our results clearly showed that OT has beneficial effect to protect kidney against IRI. The serum neopterin levels might be used as a marker to detect the degree of renal IRI.     

Oxidized LDL Accumulation in Experimental Renal Ischemia Reperfusion Injury Model

Background/Aims. The aim of this study was to identify oxidative damage of kidney during ischemia reperfusion injury (IRI) by evaluating changes in lipid peroxidation markers in tissue and blood by an experimental model. Oxidized LDL (ox-LDL) was used as an oxidative stress biomarker, whereas paraoxonase (PON-1) activity was used as an antioxidative biomarker. Methods. Sixty-three male Wistar rats were randomly assigned into three groups: renal IRI, sham, and control. In the renal IRI group, the right kidney was removed and the artery and vein of the left kidney were clamped for 90 minutes. The presence of ox-LDL in the kidney tissue sections was determined by using an immunofluorescent staining method. Results. The plasma ox-LDL levels did not increase significantly at the 24^th hour following IRI, made a peak at the 48^th hour, and declined at the 72^nd hour. Accumulation of ox-LDL was detected in the kidney tissue on the 24^th, 48^th, and 72^nd hours of the renal IRI. Serum PON-1 levels have peaked on the 24^th hour and then declined. Conclusion. This study demonstrates the accumulation of ox-LDL molecules in the renal tissues of the IRI model. Future strategies aimed to reduce the lipid peroxidation during the initial hours of renal IRI may be useful to prevent complications of ischemia.     

Pentoxifylline in Liver Ischemia and Reperfusion

ABSTRACT

Pentoxifylline is a methylxanthine compound which was first filed in 1973 and registered in 1974 in the United States by Sanofi-Aventis Deustchland Gmbh for the treatment of intermittent claudication for chronic occlusive arterial disease. This methylxanthine was later discovered to be a phosphodiesterase inhibitor. Furthermore, its hemorheological properties and its function as an inhibitor of inflammatory cytokines, like TNF-α, allowed researchers to study its effects in organ ischemia and reperfusion and transplantation. Although this drug has demonstrated beneficial effects, the mechanisms by which Pentoxifylline exerts a protective effect are not fully understood. This paper focuses on reviewing the literature to define the effect of Pentoxifylline when used in liver ischemia and reperfusion injury. Our research shows different animal models in which Pentoxifylline has been used as well as different doses and time of administration, as the ideal dose and timing have not yet been ascertained in liver ischemia and reperfusion. In conclusion, Pentoxifylline has shown positive effects in liver ischemia and reperfusion injury, and the main mechanism seems to be associated with the inhibition of TNF-α.     

Nebivolol Reduces Experimentally Induced Warm Renal Ischemia Reperfusion Injury in Rats

Ischemia/reperfusion injury, which is commonly seen in the field of renal surgery or transplantation, is a major cause of acute renal failure. The objective of the present study was to examine the role of nebivolol in modulating peroxynitrite species-induced inflammation and apoptosis after renal warm ischemia/reperfusion injury in rats. The present study was designed to investigate the effects of nebivolol on the renal warm ischemia/reperfusion injury in rats treated with the nitric oxide synthase inhibitor, N^ω-nitro-L-arginine methyl ester. After right nephrectomy, nebivolol was administered for 15 days. On the 16^th day, ischemia was induced in contra lateral kidney for 45 min, followed by reperfusion for 24 hr. Renal function, inflammation, and apoptosis were estimated at the end of 24 hr reperfusion. Nebivolol improved the renal dysfunction and reduced inflammation and apoptosis after renal ischemia/reperfusion injury. In conclusion, nebivolol shows potent anti-apoptotic and anti-inflammatory properties due to its NO-releasing property. These findings may have major implications in the treatment of human ischemic acute renal failure.     

Effects of Intravenous Anesthetics on Renal Ischemia/Reperfusion Injury

Background. Renal ischemia/reperfusion (I/R)-induced tubular epithelial cell injury, called ischemic acute renal failure, is associated with high mortality in humans. Protecting the kidney against I/R injury is very important during complicated renal operations, transplantation surgery, and anesthesia. Aim. The purpose of this study was to investigate and compare the efficiency of ketamine, thiopental, propofol, etomidate, and intralipid in reducing the injury induced by free radicals in a rat model of renal I/R. Method. Forty-two Wistar rats were divided into seven groups in our study. Rats in the sham group underwent laparotomy and waited for 120 minutes (min) without ischemia. Rats in the control group were given nothing with ischemia-reperfusion. Rats in the I/R groups were given ketamine (20 mg/kg), thiopental (20 mg/kg) propofol (25 mg/kg), etomidate (10 mg/kg) and 10% intralipid (250 mg/kg) intraperitoneally 15 min prior to the ischemia for 60 min, followed by reperfusion for 60 min. The blood samples and kidney tissues of the rats were obtained under anesthesia at the end of the reperfusion period. Biochemical malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), blood urea nitrogen (BUN), creatine (Cr), aspartate aminotransferase (AST) were determined, and histopathological analysis was performed with these samples. Results. MDA level was increased significantly in the control group (p < 0.05). Histopathological findings of the control group confirmed that there was renal impairment by tubular cell swelling, interstitial edema, medullary congestion, and tubular dilatation. MDA levels were lower in the ketamine, thiopental, and propofol groups compared to the control group (p < 0.05). In the thiopental and propofol groups, the levels of histopathological scores were significantly lower than control and etomidate groups in ischemia-reperfusion. Conclusion. Our results demonstrated that I/R injury was significantly reduced in the presence of propofol and thiopental. The protective effects of these drugs may belong to their antioxidant properties. These results may indicate that propofol and thiopental anesthesia protects against functional, biochemical, and morphological damage better than control in renal I/R injury.     

3-Aminobenzamide,a Poly ADP Ribose Polymerase Inhibitor,Attenuates Renal Ischemia/Reperfusion Injury

Introduction. This study was designed to investigate whether 3-amino benzamide (3-AB), a poly (ADP-ribose) polymerase (PARP) inhibitor, has a protective effect on kidney injury induced by renal ischemia/reperfusion (I/R) by decreasing oxidative and nitrosative stress on renal dysfunction and injury. Materials and Methods. Thirty-two male Sprague-Dawley rats were divided into four groups: sham-operated, sham-operated + 3-AB, I/R, I/R + 3-AB. Rats were given 3-AB (100 mg/kg/day ip) 14 days prior to I/R. I/R and I/R + 3-AB groups underwent 60 min of bilateral renal ischemia followed by 6 h of reperfusion. After reperfusion, kidneys and blood were obtained for evaluation. Superoxide dismutase, glutathione peroxidase, malondialdehide, protein carbonyl content, and nitrite/nitrate level (NO_x) were determined in the renal tissue. Serum creatinine (S_Cr), blood urea nitrogen (BUN), and aspartate aminotransferase (AST) were determined in the blood. Additionally, renal sections were used for histological grade of renal injury. Results. 3-AB significantly reduced the I/R-induced increases in S_Cr, BUN, and AST. In addition, 3-AB markedly reduced elevated oxidative stress product, restored decreased antioxidant enzymes, and attenuated histological alterations. Moreover, 3-AB attenuated the tissue NO_x levels, indicating reduced NO production. Conclusions. 3-AB has beneficial effect on renal glomerular and tubular dysfunction in rats' kidneys subjected to I/R injury. Moreover, 3-AB has ameliorating effect on both oxidative stress and nitrosative stress of the kidneys, which correlated with histopathological evaluation.     

The Effects of Testosterone on Intestinal Ischemia/Reperfusion in Rats

ABSTRACT

Ischemic injury to the gut is believed to occur in many serious clinical conditions. Our aim was to investigate the postischemia/reperfusion (I/R) effects of exogenously administered testosterone on the intestines of normal and orchiectomized rats.Forty-eight rats were divided into eight groups of six animals: (1) Sham-operated control group; (2) Sham-operated + testosterone-treated group; (3) I/R group: Rats were subjected to the surgical procedures and underwent intestinal ischemia for 60 min followed by reperfusion for 60 min; (4) I/R + testosterone-treated group: Rats were subjected to the surgical procedures and received testosterone 100 mg/kg (i.p.); (5) I/R + orchiectomy group: Rats were subjected to the surgical procedures as well as orchiectomy; (6) orchiectomy group: Rats were subjected to the surgical procedures as well as orchiectomy; (7) orchiectomy + testosterone-treated group: Rats were subjected to the surgical procedures as well as orchiectomy and received testosterone 100 mg/kg (i.p.); and (8) I/R + orchiectomy + testosterone-treated group. The histological findings of this study paralleled the observed degree of lipid peroxidation (LPO) and protein oxidation. Intestinal mucosal injury was extensive in the I/R, I/R + orchiectomy, and I/R + orchiectomy + testosterone groups, but was less in the I/R + testosterone group. Histopathological injury also paralleled the degree of oxidative stress. Apoptotic enterocytes were more numerous in the I/R, I/R + orchiectomy, and I/R + orchiectomy + testosterone groups. Administration of testosterone in the presence of testes significantly protected intestinal tissue against I/R mucosal injuries, while administration of testosterone in the absence of testes did not significantly protect intestinal tissue against I/R mucosal injuries.     

Alloimmune Activation Enhances Innate Tissue Inflammation/Injury in a Mouse Model of Liver Ischemia/Reperfusion Injury

The deleterious sensitization to donor MHC Ags represents one of the most challenging problems in clinical organ transplantation. Although the role of effector/memory T cells in the rejection cascade has been extensively studied, it remains unknown whether and how these ‘Ag‐specific’ cells influence host innate immunity, such as tissue inflammation associated with ischemia and reperfusion injury (IRI). In this study, we analyzed how allogeneic skin transplant (Tx) affected the sequel of host's own liver damage induced by partial warm ischemia and reperfusion. Our data clearly showed that allo‐Tx recipients had increased inflammatory response against IR insult in their native livers, as evidenced by significantly more severe hepatocelluar damage, compared with syngeneic Tx recipient controls, and determined by serum ALT levels, liver histology (Suzuki's score) and intrahepatic proinflammatory gene inductions (TNF‐α, IL‐1β and CXCL10). The CD4 T cells, but neither CD8 nor NK cells, mediated the detrimental effect of allo‐Ag sensitization in liver IRI. Furthermore, CD154, but not IFN‐γ, was the key mechanism in allo‐Tx recipients to facilitate IR‐triggered liver damage. These results provide new evidence that alloreactive CD4 T cells are capable of enhancing innate tissue inflammation and organ injury via an Ag‐nonspecific CD154‐dependent but IFN‐γ independent mechanism.     

新霉素对脑缺血再灌注损伤的保护作用

目的：探讨钙及磷酯酶Ｃ（ＰＬＣ）在脑缺血再灌注损伤中的作用机制及ＰＬＣ抑制剂新霉素是否通过抑制ＰＬＣ活性而起脑保护作用。方法：和放血降压法建立大鼠全脑缺血模型，采用原子吸收光谱法及干湿法测定缺血再灌注后脑组织含钙量。含水量变化及新霉素对其影响。结果：再灌组含钙量、含水量较对照组升高（Ｐ〈０．０５）；再灌组内随灌注时间延长，脑组织含钙量、含水量增高（Ｐ〈０．０５）；给药组含钙量、含水量均较再灌组降低     

人参皂甙Rb1对肺缺血再灌注损伤的保护作用

目的探讨人参皂甙Ｒｂ１对肺缺血再灌注损伤的保护作用。方法按肺移植供肺获取和保存的方法，对３５只家兔的肺分别获取，保存；然后采用体外装置，建立体外肺缺血再灌注损伤模型。在即将再灌流前，将不同剂量的Ｒｂ１加入到５０ｍｌ再灌流血液中。结果Ｒｂ１可使肺组织中超氧化物歧化酶（ＳＯＤ）含量升高，丙二醛（ＭＤＡ）含量降低；使肺动脉压（ＰＡＰ）降低，湿肺干肺比重降低和改善肺组织病理变化。Ｒｂ１在再灌流血液中浓度为８０ｍｇ／Ｌ时，已有明显效果。结论Ｒｂ１对肺缺血再灌注损伤具有明显的保护作用。     

Summary of FDA Workshop on Ischemia Reperfusion Injury in Kidney Transplantation

The Food and Drug Administration (FDA) held an open public workshop in September 2011 to discuss the current state of science related to the effects of ischemia reperfusion injury (IRI) on outcomes in kidney transplantation. Topics included the development of IRI and delayed graft function (DGF), histology and biomarkers, donor factors, recipient factors, organ quality and organ preservation by means of cold storage solutions or machine perfusion. Various mechanisms of injury and maladaptive response to IRI were discussed as potential targets of intervention. Animal models evaluating specific pathophysiological pathways were presented, as were the limitations of extrapolating animal results to humans. Clinical trials of various drug products administered in the peri‐transplant period were summarized; a few demonstrated early improvements in DGF, but none demonstrated an improvement in late graft function. Clinical trial design for IRI and DGF were also discussed.