Oxytocin alleviates hepatic ischemia-reperfusion injury in rats

Various mechanisms have been proposed for the pathogenesis of postischemic hepatic injury, including the generation of reactive oxygen metabolites. Oxytocin (OT) possesses antisecretory, antiulcer effects, facilitates wound healing and has anti-inflammatory properties. Hepatic ischemia-reperfusion (I/R)-injury was induced by inflow occlusion to median and left liver lobes ( approximately 70%) for 30 min of ischemia followed by 1h reperfusion in female Sprague-Dawley rats under anesthesia. I/R group (n=8) was administered intraperitoneally either OT (500 microg/kg) or saline at 24 and 12 h before I/R and immediately before reperfusion. Sham-operated group that underwent laparotomy without hepatic ischemia served as the control. Rats were decapitated at the end of reperfusion period. Hepatic samples were obtained for the measurement of myeloperoxidase (MPO) activity, malondialdehyde (MDA), glutathione (GSH) and collagen levels and histopathological analysis. Tumor necrosis factor-alfa (TNF-alpha) and transaminases (SGOT, SGPT) were assayed in serum samples. I/R injury caused significant increases in hepatic microscopic damage scores, MPO activity, collagen levels, transaminase, serum TNF-alpha levels. Oxytocin treatment significantly reversed the I/R-induced elevations in serum transaminase and TNF-alpha levels and in hepatic MPO and collagen levels, and reduced the hepatic damage scores. OT treatment had tendency to abolish I/R-induced increase in MDA levels, while GSH levels were not altered. These results suggest that OT has a protective role in hepatic I/R injury and its protective effect in the liver appears to be dependent on its inhibitory effect on neutrophil infiltration.     

Mesna (2-mercaptoethane sulfonate) prevents ischemia/reperfusion induced renal oxidative damage in rats

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.     

Oxytocin alleviates oxidative renal injury in pyelonephritic rats via a neutrophil-dependent mechanism

BACKGROUND: Urinary tract infection (UTI) may cause inflammation of the renal parenchyma and may lead to impairment in renal function and scar formation. Oxidant injury and reactive oxygen species (ROS) have been found responsible in the pathogenesis of UTI. The neurohypophyseal hormone oxytocin (OT) facilitates wound healing and is involved in the modulation of immune and inflammatory processes. We investigated the possible therapeutic effects of OT against Escherichia coli induced pyelonephritis in rats both in the acute and chronic setting. METHODS: Twenty-four Wistar rats were injected 0.1 ml solution containing E. coli ATCC 25922 10(10) colony forming units/ml into left renal medullae. Six rats were designed as sham group and were given 0.1 ml 0.9% NaCl. Pyelonephritic rats were treated with either saline or OT immediately after surgery and at daily intervals. Half of the pyelonephritic rats were decapitated at the 24th hour of E. coli infection, and the rest were followed for 7 days. Renal function tests (urea, creatinine), systemic inflammation markers [lactate dehydrogenase (LDH) and tumor necrosis factor alpha (TNF-alpha)] and renal tissue malondialdehyde (MDA) as an end product of lipid peroxidation, glutathione (GSH) as an antioxidant parameter and myeloperoxidase (MPO) as an indirect index of neutrophil infiltration were studied. RESULTS: Blood urea, creatinine, and TNF-alpha levels were increased, renal tissue MDA and MPO levels were elevated and GSH levels were decreased in both of the pyelonephritic (acute and chronic) rats. All of these parameters and elevation of LDH at the late phase were all reversed to normal levels by OT treatment. CONCLUSION: OT alleviates oxidant renal injury in pyelonephritic rats by its anti-oxidant actions and by preventing free radical damaging cascades that involves excessive infiltration of neutrophils.     

缺血预处理对肢体缺血/再灌注大鼠胃粘膜损伤的保护效应

目的：观察肢体缺血再灌注（LI／R）对胃粘膜的损伤作用及缺血预处理对其影响,探讨胃粘膜损伤的机制及缺血预处理（IPC）的作用机理。方法：观察并测定肢体缺血4h再灌注4h后以及应用肢体缺血预处理干预后各组胃粘膜损伤指数,胃结合粘液量;检测胃粘膜中髓过氧化物酶（MPO）、超氧化物歧化酶（SOD）、丙二醛（MDA）、黄嘌呤氧化酶（XOD）含量的变化以及血浆中乳酸脱氢酶（LDH）的含量变化。结果：大鼠LI／R后胃粘膜损伤指数增加;胃结合粘液量较对照组显著下降;胃粘膜中MPO、MDA、XOD的值均较对照组增加,血浆中LDH的含量亦较对照组显著增加,胃粘膜组织中SOD的酶活力下降;IPC组与LIR组对比,胃结合粘液量较LIR组显著增加：胃粘膜损伤指数、胃粘膜中MPO的含量、以及胃粘膜中MDA、XOD、LDH均较LI／R组明显降低;胃粘膜中SOD酶活力增强。结论：LI／R作为应激原可引起胃粘膜损伤,导致应激性溃疡的发生;自由基在肢体缺血再／灌注后继发胃粘膜损伤过程中发挥作用。缺血预处理可减轻肢体缺血再灌注后的胃粘膜损伤,其作用机制可能是通过减少自由基的产生而发挥其保护作用。     

Oxytocin ameliorates oxidative colonic inflammation by a neutrophil-dependent mechanism

Oxytocin (OT), a nonapeptide produced in the paraventricular and the supraoptical nuclei in the hypothalamus has a wide range of effects in the body. However, the role of OT on the gastrointestinal (GI) tract has to be settled. OT may participate in the regulation of motility, secretion, blood flow, cell turnover and release of neurotransmitters and/or peptides in the GI tract, possesses antisecretory and antiulcer effects, facilitates wound healing and is involved in the modulation of immune and inflammatory processes. The present work was conducted to assess the possible therapeutic effects of OT against the acetic acid-induced colonic injury in the rat. METHODS: Colitis was induced by intracolonic administration of acetic acid (5%) in Sprague-Dawley rats (200-250 g). Either saline or OT (0.5 mg/kg) was injected subcutaneously, immediately after the induction of colitis and repeated two times a day for 4 days. On the 4th day, rats were decapitated and distal 8 cm of the colon were removed for the macroscopic and microscopic damage scoring, determination of tissue wet weight index (WI), malondialdehyde (MDA) levels, an end product of lipid peroxidation; glutathione (GSH) levels, a key antioxidant; and myeloperoxidase (MPO) activity, as an indirect index of neutrophil infiltration. Colonic collagen content, as a fibrosis marker was also determined. Lactate dehydrogenase (LDH) and tumor necrosis factor-alpha (TNF-alpha) levels were assayed in serum samples. In the acetic acid-induced colitis, macroscopic and microscopic damage scores, WI, MDA and MPO levels were significantly increased, while GSH levels were decreased when compared to control group (p <0.05-<0.001). Treatment with OT abolished the colitis-induced elevations in damage scores, WI, MDA and MPO levels and restored the GSH levels (p <0.05-0.001). Similarly, acetic acid increased the collagen content of colonic tissues and OT-treatment reduced this value to the level of the control group. Serum LDH and TNF-alpha levels were also elevated in the acetic acid-induced colitis group as compared to control group, while this increase was significantly decreased by OT treatment. The results suggest that OT, which improves the antioxidative state of the colonic tissue and ameliorates oxidative colonic injury via a neutrophil-dependent mechanism, requires further investigation as a potential therapeutic agent in colonic inflammation.     

Octreotide: a new approach to the management of acute abdominal hypertension

Acutely increased intra-abdominal pressure (IAP) may lead to abdominal compartment syndrome (ACS), which ischaemia/reperfusion (I/R) injury plays an important role. The main goal of the management of ACS is to lower the intra-abdominal pressure despite reperfusion injury. Octreotide (OCT), a synthetic somatostatin analogue, lowers the splanchnic perfusion. The aim of this study was to investigate whether OCT improves the reperfusion injury after decompression of acute abdominal hypertension.Under anesthesia, a catheter was inserted intraperitoneally and using an aneroid manometer connected to the catheter, IAP was kept at 20 mmHg (ischemia group; I) for 1h. In the I/R group, pressure applied for an hour was decompressed and 1h reperfusion period was allowed. In another group of I/R, OCT was administered (50 microg/kg i.p.) immediately before the decompression of IAP. The results demonstrate that kidney and lung tissues of malondialdehyde (MDA; an end product of lipid peroxidation) levels and myeloperoxidase (MPO; index of tissue neutrophil infiltration) activity were elevated, while glutathione (GSH; a key to antioxidant) levels were reduced in I/R group (P<0.001). Moreover, OCT treatment applied in the I/R group reduced the elevations in blood urea nitrogen (BUN) and serum creatinine levels. Our results implicate that IAP causes oxidative organ damage and OCT, by reducing splanchnic perfusion and controlling the reperfusion of abdominal organs, could improve the reperfusion-induced oxidative damage. Therefore, its therapeutic role as a "reperfusion injury-limiting" agent must be further elucidated in IAP-induced abdominal organ injury.     

Protective effect of hesperidin against lung injury induced by intestinal ischemia/reperfusion in adult albino rats: Histological,immunohistochemical and biochemical study

Hesperidin is a naturally common flavonoid. It is an abundant and cheap by-product of citrus cultivation. It is reported to have antioxidative, anti-inflammatory and anticarcinogenic effects. This work was performed to investigate the possible protective role of hesperidin in ameliorating the effect of experimentally induced intestinal ischemia/reperfusion injury (I/R) on lung tissue, histologically, immunohistochemically and biochemically. Thirty male Wistar adult albino rats were randomized into three groups named: group I (control group); group II (I/R); and group III (I/R with hesperidin). Intestinal I/R was induced by occluding the superior mesenteric artery for 60 min, followed by 120 min of reperfusion period. Animals were given hesperidin orally 1 h before the onset of ischemia. At the end of the reperfusion period the lung tissues were extracted for histopathological examination and immunohistochemical detection of the distribution of inducible nitric oxide synthase (iNOS). Pulmonary edema was evaluated by lung tissue wet/dry weight ratios. The levels of malondialdehyde (MDA, a biomarker of oxidative damage), myeloperoxidase (MPO, an index of the degree of neutrophil accumulation) and glutathione (GSH, a biomarker of protective oxidative injury) were also determined in all dissected tissues. Pretreatment with hesperidin (in group III) alleviated lung morphological changes noticed in I/R group and the levels of MDA and MPO were significantly decreased whereas those of GSH were significantly increased. Immunohistochemical study revealed a significant decrease in the iNOS. Hesperidin also significantly alleviated the formation of pulmonary edema as evidenced by the decreased organ wet/dry weight ratios. Hesperidin exerts a protective effect against lung damage induced by intestinal I/R injury in rats by reducing oxidative stress.     

Attenuation of ischemia/reperfusion-induced intestinal injury by oleo-resin from Copaifera langsdorffii in rats

Copaifera langsdorffii oleo-resin (CLOR) is a reputed herbal medicine used to combat gastrointestinal functional disorders. Our previous studies show that CLOR prevents gastric ulceration and promotes wound healing. This study examined the effects of CLOR on intestinal damage associated with mesenteric ischemia/reperfusion in rat. Wistar albino rats were divided into four groups of six in each. Group 1: Sham operated, Group 2: Vehicle + 45 min of ischemia followed by 60 min reperfusion (I/R), Groups 3 and 4: I/R + CLOR (200 and 400 mg /kg, p.o., respectively). All treatments were given 24 h, 12 h and 2 h before I/R. Animals were sacrificed at the end of reperfusion period and ileal tissue samples were obtained for biochemical analysis. Myeloperoxidase (MPO), an index of polymorphonuclear leukocytes; malondialdehyde (MDA), an end product of lipoperoxidation; catalase (CAT), an antioxidant enzyme; reduced glutathione (GSH), a key antioxidant; and nitrite, a marker of nitric oxide (NO) production were determined in ileum homogenates. The results show that I/R produces a significant increase in MDA content, MPO, and CAT activities with a significant decrease in GSH and an elevation in nitrite production, as compared to sham control. CLOR treatment caused significant attenuations in I/R-associated increases of MPO, MDA and CAT activities and on nitrite level. Besides, CLOR could effectively prevent the I/R-associated depletion of GSH. The data indicate that the oleo-resin has a protective action against I/R-induced intestinal tissue damage, which appeared to be, at least in part, due to an antioxidant and anti-lipid peroxidation mechanism.     

The effects of PDE5 inhibitory drugs on renal ischemia/reperfusion injury in rats

The aim of the present study was to evaluate the effects of phosphodiesterase type 5 (PDE5) inhibitory drugs, Tadalafil and Sildenafil, on inducible NOS (iNOS), endothelial NOS (eNOS) and p53 genes expressions and apoptosis in ischemia/reperfusion (I/R) induced oxidative injury in rat renal tissue. Eighty Sprague-Dawley rats (300-350?g) were divided into four groups. In ischemia/reperfusion group, rats were subjected to renal ischemia by clamping the left pedicle for 60?min, and then reperfused for 90?min. On the other hand, in other two groups the rats were individually pretreated with Tadalafil and Sildenafil 1?h before the induction of ischemia. Malondialdehyde (MDA) is determined in renal tissue homogenates by high-performance liquid chromatography, the number of apoptotic cell were calculated by TUNEL method and p53 and eNOS expression were detected with immunohistochemistry. On the other hand, myeloperoxidase (MPO) levels were measured by spectrophotometric method and the mRNA level of iNOS in renal tissue was determined by Real-time PCR (RT-PCR). Our results indicate that MDA and MPO levels were increased in the I/R group than those in the control group. Both Tadalafil and Sildenafil treatment decreased the MDA levels in ischemia/reperfusion group, whereas this effect was more potent with Sildenafil. RT-PCR results showed that, iNOS gen expression increased in the I/R group, but decreased in the PDE5 inhibitory drugs treated group. Apoptotic cells, eNOS levels and p53 positive cells were also decreased in PDE5 inhibitory drugs treated group. We suggest that Tadalafil and Sildenafil have beneficial effects against I/R related renal tissue injury and this protective effect is clearer for Sildenafil than Tadalafil.     

Quercetin treatment against ischemia/reperfusion injury in rat corpus cavernosum tissue: a role on apoptosis and oxidative stress

Abstract

Reactive oxygen metabolites play an important role in the ischemia/reperfusion (I/R)-induced tissue injury. This study was designed to investigate the possible protective effects of quercetin against I/R injury of the rat corpus cavernosum tissue. To induce I/R injury, abdominal aorta was clamped for 30 min and reperfused for 60 min. Quercetin (20 mg/kg) or vehicle was given before ischemia and just after reperfusion in the I/R group and in the sham-operated control group in which clamping was not performed. After decapitation, corpus cavernosum tissues were removed and either placed in organ baths or stored for evaluating biochemical parameters. Oxidative injury was examined by measuring lucigenin chemiluminescence (CL), nitric oxide (NO), malondialdehyde (MDA) and glutathione (GSH) levels, superoxide dismutase (SOD) and myeloperoxidase (MPO) activities and caspase-3 protein levels. In the I/R group, contractile responses to phenylephrine and relaxation responses to carbachol were impaired significantly compared with those in the control groups, while quercetin treatment in I/R group reversed both of the responses. On the other hand, increase in lucigenin CL, NO, MDA levels and MPO and caspase-3 activities and decrease in GSH levels and SOD activity in the cavernosal tissues of the I/R group were also significantly reversed by quercetin treatment. Furthermore, observed distorted morphology with ruptured endothelial cells and vacuolization in the cytoplasm of cavernosal tissues of I/R no longer persisted in the quercetin-treated I/R group. Thus, our results suggested that treatment with quercetin may have some benefits in controlling I/R-induced tissue injury through its anti-inflammatory, anti-apoptotic, and antioxidant effects.     

Melatonin and N-acetylcysteine have beneficial effects during hepatic ischemia and reperfusion

This study was designed to study the effects of Melatonin (Mel) and N-Acetylcystein (NAC) on hepatic ischemia/reperfusion (I/R) injury in rats. For this purpose Wistar albino rats were subjected to 45 minutes of hepatic ischemia followed by 60 minutes of reperfusion period. Melatonin (10 mg/kg) or NAC (150 mg/kg) were administered alone or in combination, intraperitoneally, 15 minutes prior to ischemia and just before reperfusion. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were determined to assess liver functions. Liver tissues were taken for determination of malondialdehyde (MDA) levels, an end product of lipid peroxidation; glutathione (GSH) levels, a key antioxidant; protein carbonyl concentration (protein oxidation) (PO), a specific marker of oxidative damage of proteins; and myeloperoxidase (MPO) activity, as an indirect index of neutrophil infiltration. Plasma ALT and AST activities were higher in ischemia/reperfusion group than in control. They were decreased in the groups given Mel, NAC or the combination. Hepatic GSH levels, significantly depressed by I/R, were elevated to control levels in the combination group, whereas treatment with Mel or NAC alone provided only a limited protection. Hepatic MDA and PO levels, and MPO activity were significantly increased by I/R. The increase in these parameters were partially decreased by Mel or NAC alone, whereas treatment with the combination reduced these values back to control levels. In conclusion, considering the dosages used, Mel appeared to be significantly more potent than NAC in reversing the oxidative damage induced by I/R. Our findings show that Mel and NAC have beneficial effects against the I/R injury and due to their synergistic effects, when administered in combination, may have a more pronounced protective effects on the liver.     

一氧化氮、内皮素-1对大鼠肢体缺血/再灌注后脑损伤的影响

目的: 研究一氧化氮(NO)和内皮素-1(ET-1)在大鼠肢体缺血/再灌注(LI/R)后脑损伤中的作用,探讨NO/ET-1平衡关系的变化对脑损伤的影响.方法: 在大鼠LI/R损伤模型上,应用NO合成前体物质L-精氨酸(L-Arg)、一氧化氮合酶(NOS)抑制剂氨基胍(AG)、ETA受体阻断剂BQl23进行干预,观察血浆 NO、ET-1、MDA、XOD、SOD、LDH及脑组织tNOS、iNOS、cNOS、NO、ET-1、MDA、XOD、MPO、 SOD的变化.结果: 与对照组比较,I/R组血浆MDA、XOD、LDH及脑组织MDA、XOD、MPO升高,SOD活性降低(P<0.01),脑组织tNOS和iNOS明显升高,而cNOS明显降低(P<0.01),I/R组血浆及脑组织NO、ET-1增加,NO/ET-1比值降低,脑损伤加重.应用L-Arg及BQ123后,血浆及脑组织NO/ET-1比值较I/R组升高,脑损伤减轻,应用AG后,NO/ET-1比值降低,脑损伤进一步加重.结论: 肢体缺血/再灌注后,一氧化氮与内皮素-l的比值降低时脑损伤加重.     

丙酮酸钠对失血性休克大鼠缺血/再灌注损伤的保护作用

目的:研究丙酮酸钠对失血性休克后缺血/再灌注损伤的保护作用。方法:制作失血性休克大鼠模型,回输全血,同时分别给予生理盐水、谷胱甘肽和丙酮酸钠适量,于再灌注后3h处死动物。检测血浆乳酸脱氢酶(LDH)和谷草转氨酶(GOT)的活性、组织丙二醛(MDA)的含量和髓过氧化物酶(MPO)的活性,观察心、肝、肺和肾组织的病理变化。结果:丙酮酸钠组与生理盐水组相比,血浆LDH和GOT的活性降低,肝、肺和肾组织MDA的含量下降,心、肺和肾组织MPO活性降低,效果优于谷胱甘肽。心、肝、肺和肾组织形态学观察显示,丙酮酸钠使组织损伤减轻。结论:丙酮酸钠对失血性休克后再灌注损伤具有保护作用。其作用机制可能与清除氧自由基、减少中性粒细胞的浸润、减轻炎性反应有关。     

Effect of leptin on renal ischemia-reperfusion damage in rats

Tumor necrosis factor-alpha (TNF-alpha) has been established as an important mediator in renal ischemia-reperfusion (I/R) injury. Leptin, a product of the ob gene, has been known to exhibit cytoprotective effects on renal tissue, but its effect on renal tissue TNF-alpha level after renal I/R injury in rats remains unknown. The purpose of the study was to evaluate the effects of leptin on renal tissue TNF-alpha, malondialdehyde (MDA), protein carbonyls (PCs) and total sulfydryl group (SH) levels, and plasma nitrite levels after renal I/R injury in rats. The animals were divided into three groups: control, I/R and I/R+leptin. Rats were subjected to renal ischemia by clamping the left pedicle for 45 min, and then reperfused for 1 h. The I/R+leptin group was pretreated intraperitoneally with leptin (10 microg/kg) 30 min before the induction of ischemia. Our results indicate that MDA, TNF-alpha levels, and PCs were significantly higher in the I/R group than those in the control group (p < 0.05). The administration of leptin decreased these parameters (p < 0.05) significantly. The SH level was observed to significantly decrease after I/R injury when compared to the control group (p < 0.05). Leptin treatment significantly increased tissue SH and plasma nitrite levels when compared to the I/R group (p < 0.05). Plasma nitrite levels did not change significantly in I/R when compared to the control. These results suggest that leptin could exert a protective effect on I/R induced renal damage by decreasing TNF-alpha levels and increasing nitrite level.     

Protective effects of leptin on ischemia/reperfusion injury in rat bladder

The aim of the study was to evaluate protective effects of exogenous leptin on ischemia/reperfusion (I/R)-induced injuries to the urinary bladder tissue and to investigate the effect on tumor necrosis factor alpha (TNF-alpha) levels and apoptotic cells during I/R injury. Bladder I/R injury was induced by abdominal aorta occlusion by ischemia for 45 min, followed by 60 min of reperfusion in rats. The rats were divided into three groups: control (n = 8 + 8), I/R (n = 8 + 8) and I/R+leptin group (n = 8 + 8). The rats in the I/R+leptin group were treated intraperitoneally with leptin (10 microg/kg) 60 min prior to ischemia induction. At the end of the reperfusion period, urinary bladders of the first eight rats from each group were removed for TUNEL staining processing while the others were removed for biochemical analyses for MDA and TNF-alpha levels. In the I/R group, the ratios of TUNEL-positive nuclei were higher than the control and the I/R+leptin groups. The MDA and TNF-alpha levels of the bladder tissue in the I/R group were higher than the control and leptin-treated groups. TUNEL-staining and biochemical studies revealed that leptin has a protective effect on urinary bladder I/R injury.     

Chronic renal failure-induced multiple-organ injury in rats is alleviated by the selective CysLT1 receptor antagonist montelukast

Chronic renal failure (CRF) is associated with oxidative stress that promotes production of reactive oxygen species and cytokine release. We aimed to investigate the possible protective effect of montelukast, a CysLT1 receptor antagonist, against oxidative damage in a rat model of CRF, induced by 5/6 reduction of renal mass. Male Wistar albino rats were randomly assigned to either the CRF group or the sham-operated control group, which received saline or montelukast (10mg/kg, i.p.) for 4 weeks. At the end of the 4 weeks, rats were decapitated and trunk blood was collected. Creatinine, blood urea nitrogen and lactate dehydrogenase (LDH) activity were measured in the serum samples, while leukotriene B(4), TNF-alpha, IL-1 beta, IL-6, total antioxidant capacity (AOC) and leukocyte apoptosis were assayed in plasma samples. Kidney, lung, heart and brain tissue samples were taken for the determination of tissue malondialdehyde (MDA), glutathione (GSH) levels, and myeloperoxidase (MPO) activity. Oxidant-induced tissue fibrosis was determined by tissue collagen contents, and the extent of tissue injuries was analyzed microscopically. CRF caused significant decreases in tissue GSH and plasma AOC, which were accompanied with significant increases in MDA levels, MPO activities, and collagen contents of all the studied tissues, while the circulating levels of the pro-inflammatory mediators, LDH activity, creatinine and BUN were elevated. Montelukast treatment reversed all these biochemical indices, as well as histopathological alterations induced by CRF. Similarly, flow cytometric measurements revealed that leukocyte apoptosis was increased in CRF group, while montelukast reversed this effect. In conclusion, CRF-induced oxidative tissue injury occurs via the activation of pro-inflammatory mediators and by neutrophil infiltration into tissues, and that protective effects of montelukast on CRF-induced injury can be attributed to its ability to inhibit neutrophil infiltration and apoptosis, to balance oxidant-antioxidant status and to regulate the generation of pro-inflammatory mediators.     

The effects of desferrioxamine and quercetin on hepatic ischemia-reperfusion induced renal disturbance

BACKGROUND: The aim of this study was to analyze the effects of 45min of hepatic ischemia and 1h of reperfusion on renal oxidative stress parameters, on renal tissue damage, and the role of Desferrioxamin (Dfx) and Q on these parameters. METHODS: Thirty Wistar albino rats were randomized to five groups. Group I was the control group. Group II received no treatment. Groups III and IV received intramuscular injections of desferrioxamine (100mg/kg) and quercetin (50mg/kg), respectively. Group V was administered Dfx and quercetin in combination. After treatment for 3 days, groups II, III, IV, and V were exposed to total hepatic ischemia for 45min. Plasma alanine aminotransferase levels, renal malondialdehyde and reduced glutathione (GSH) activities were measured after reperfusion for 1h. Histopathological and ultrastructural analysis of renal tissues was carried out. RESULTS: Plasma creatinine and BUN levels were markedly increased in the IR group and pretreated groups. Kidney MDA increased in the IR group, Q and Dfx+Q significantly decreased kidney MDA Kidney GSH levels markedly decreased in the IR group, Dfx significantly increased kidney GSH. No evidence of overt injury was observed in any renal tissue under light and electron microscopy. CONCLUSIONS: Our data demonstrated that 45min of hepatic ischemia and 1h of reperfusion may alter renal functions and may cause oxidative stress on renal tissue. Q and Dfx seem to have a beneficial effect via the GSH system and modulation of MDA levels.     

The protective effect of oxytocin on ischemia/reperfusion injury in rat urinary bladder

Oxytocin (OXY), a well-known nonapeptide, plays a crucial role in reproduction, and has effects on modulating the immune and inflammatory processes in living organisms as well. Recently it is also known as an antioxidant in several organs. The present study aims to demonstrate the protective effect of OXY against ischemia/reperfusion (I/R) injury in urinary bladder tissue. Abdominal aorta of rats, were clamped to perform urinary bladder ischemia. OXY (0.5 μg/kg) was injected intraperitoneally before ischemia in I/R + OXY group, whereas the vehicle solution was injected to I/R group. At the end of reperfusion, tissue samples from urinary bladder were processed for histochemical, ultrastructural and biochemical analysis. Tissue sections were stained by toluidine blue for mast cell counting and hematoxylin–eosin for histopathology. In addition, malondialdehyde (MDA) and glutathione (GSH) levels were determined biochemically. The results demonstrated that there was an extreme damage at urothelium, dilatation of intercellular junctions, inflammatory cell infiltration in I/R group. I/R + OXY group demonstrated a reduction in the severity of urinary bladder damage. According to mast cell counting results, both granulated and degranulated mast cells were decreased in I/R + OXY group compared to I/R group. The mean MDA level was higher in I/R group compared to control and lower in I/R + OXY group compared to I/R group. GSH level reduced in I/R group compared to the control and increased in I/R + OXY group compared to I/R group. In conclusion, oxytocin, as confirmed by histological evaluation and biochemical assays has a potential protective effect in the urinary bladder tissue against ischemia/reperfusion injury.     

Ghrelin improves burn-induced multiple organ injury by depressing neutrophil infiltration and the release of pro-inflammatory cytokines

Mechanisms of burn-induced skin and remote organ injury involve oxidant generation and the release of pro-inflammatory cytokines. In this study the possible antioxidant and anti-inflammatory effects of ghrelin were evaluated in a rat model of thermal trauma. Wistar albino rats were exposed to 90 degrees C bath for 10 s to induce thermal trauma. Ghrelin, was administered subcutaneously (10 ng/kg/day) after the burn injury and repeated twice daily. Rats were decapitated at 6 h and 48 h after burn injury and blood was collected for the analysis of pro-inflammatory cytokines (TNF-alpha and IL-1beta), lactate dehydrogenase (LDH) activity and antioxidant capacity (AOC). In skin, lung and stomach tissue samples malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) and Na(+)-K(+)-ATPase activity were measured in addition to the histological analysis. DNA fragmentation ratio in the gastric mucosa was also evaluated. Burn injury caused significant increase in both cytokine levels, and LDH activity, while plasma AOC was found to be depleted after thermal trauma. On the other hand, in tissue samples the raised MDA levels, MPO activity and reduced GSH levels, Na(+)-K(+)-ATPase activity due to burn injury were found at control levels in ghrelin-treated groups, while DNA fragmentation in the gastric tissue was also reduced. According to the findings of the present study, ghrelin possesses a neutrophil-dependent anti-inflammatory effect that prevents burn-induced damage in skin and remote organs and protects against oxidative organ damage.     

大鼠肢体缺血/再灌注后肺损伤及一氧化氮合酶的变化与意义

目的：研究大鼠肢体缺血／再灌注后急性肺损伤时,内皮型一氧化氮合酶（eNOS）和诱导型一氧化氮合酶（i-NOS）的表达及其在急性肺损伤发生中的作用。方法：雄性Wistar大鼠于后肢根部阻断血流后松解（4h／4h）,分别给予L-Arg和氨基胍（AG）预先干预,分为control、IR、L-Arg和AG组,免疫组织化学方法检测肺组织中iNOS和eNOS的表达,同时检测肺组织中MDA、MPO、W／D和NO2^-／NO3^-值,肺组织形态学观察以评价肺损伤的程度。结果：与control组比较,I／R组eNOS表达降低,iNOS表达增强,MDA、MPO、W／D和NO2^-／NO3^-值增加。肺组织充血、炎细胞浸润,肺泡腔渗液;与I／R组比较,L-Arg组eNOS、iNOS表达无明显变化,NO2^-／NO3^-增加。MDA、MPO、W／D降低,肺组织损伤有减轻趋势,AG组eNOS表达无明显变化,iNOS活性降低,NO2^-／NO3^-减少,MDA、MPO、W／D增加,肺组织损伤有加重趋势。结论：肢体缺血／再灌注急性肺损伤过程中,iNOS表达增加,NO生成增多,在肺损伤发生中有一定的保护作用。