Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0920646 (renal ischemia)
 2,515 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Renal ischemia is of clinical interest because of its role in renal failure and also renal graft rejection. To evaluate the effect of the combination of N-acetylcysteine (NAC), a potent antioxidant, sodium nitroprusside (SNP), a nitric oxide donor, and phosphoramidon (P), an endothelin converting enzyme inhibitor, on tissue protection against ischemia-reperfusion injury, we studied the biochemical and morphological changes due to 90 min of renal ischemia-reperfusion in the rat model. Ninety min of ischemia caused very severe injury and the animals could not survive after 4 days without any treatment. Whereas, animals in the treated groups survived i.e. the NAC group (25%), NAC + SNP group (43%) and in the NAC + SNP + P group (100%), 2 weeks after 90 min of ischemia. A significant increase in the serum levels of creatinine and urea nitrogen was shown in the untreated group and to a much lesser extent in the treated group, especially in the NAC + SNP + P group. The protective effect was also supported by light microscopic studies on renal tissue sections. We also measured the activities of antioxidant enzymes in tissue homogenates. With the exception of Mn-superoxide dismutase, the activities of antioxidant enzymes (catalase, glutathione peroxidase, CuZn-superoxide dismutase) were decreased in the untreated kidney. The administration of NAC alone and NAC + SNP protected against the loss of activities. Treatment with a combination of NAC, SNP and P showed a synergistic effect as evidenced by the best protection. These results suggest that pre-administration of a combination of antioxidant (NAC) with endothelin derived vasodilators (sodium nitroprusside and Phosphoramidon) attenuates renal ischemia-reperfusion injury, e.g. in donor kidney for transplantation, by protecting cells against free radical damage.
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PMID:Combination therapy of N-acetylcysteine, sodium nitroprusside and phosphoramidon attenuates ischemia-reperfusion injury in rat kidney. 1248 67

The effect of Wen-Pi-Tang extract on renal injury induced by peroxynitrite (ONOO-) production was investigated using rats subjected to intravenous lipopolysaccharide (LPS) injection and then renal ischemia followed by reperfusion. The plasma level of 3-nitrotyrosine, a marker of cytotoxic ONOO formation in vivo, was enhanced markedly in control rats subjected to LPS plus ischemia-reperfusion, but was significantly reduced by the oral administration of Wen-Pi-Tang extract, at doses of 62.5 and 125 mg/kg body weight/day, for 30 days prior to LPS plus ischemia-reperfusion. The activities of inducible nitric oxide synthase (iNOS) and xanthine oxidase (XOD) in renal tissue of control and Wen-Pi-Tang extract-treated rats did not change significantly, while those of the antioxidant enzymes, superoxide dismutase, catalase and glutathione peroxidase, were significantly increased by the administration of Wen-Pi-Tang extract, indicating that Wen-Pi-Tang improved the defense system by scavenging free radicals, not by directly inhibiting nitric oxide and superoxide production by iNOS and XOD. In addition, the levels of the hydroxylated products, m- and p-tyrosine, declined, whereas that of phenylalanine increased, after oral administration of Wen-Pi-Tang extract. Furthermore, the elevated plasma urea nitrogen and creatinine levels resulting from LPS plus ischemia-reperfusion process were significantly reduced by Wen-Pi-Tang extract, implying amelioration of renal impairment. The present study indicates that Wen-Pi-Tang extract contributes to the regulation of ONOO- formation and plays a beneficial role against ONOO(-) -induced oxidative injury and renal dysfunction in vivo.
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PMID:Prevention of peroxynitrite-induced renal injury through modulation of peroxynitrite production by the Chinese prescription Wen-Pi-Tang. 1260 16

This study evaluated the effects of dehydroepiandrosterone (DHEA) on the oxidant [malondialdehyde (MDA)] and antioxidant [superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and glutathione (GSH)] systems in liver after renal ischemia-reperfusion (IR) injury in rabbits. Thirty rabbits were randomly assigned to 3 groups of 10: group I (sham operation), group II (renal IR group), and group III (DHEA, 25 mg/kg, s.c., 15 min pre-ischemia). Renal IR injury in group II caused a decrease of SOD (25%), GPx (36%), and CAT (26%) activities and GSH levels (32%), and increases of MDA (30%) in liver and of ALT and AST activities in serum, compared to group I. DHEA administration decreased the hepatic MDA level (19%) and serum ALT activity (30%) (p <0.01 and p <0.05, respectively), and considerably increased hepatic GSH levels and GPx activities (p <0.01 for both) in group III, compared to group II. These results suggest that DHEA treatment has beneficial effects on antioxidant defenses against hepatic injury after renal IR in rabbits, possibly by augmenting GSH levels and lowering MDA production.
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PMID:Dehydroepiandrosterone improves hepatic antioxidant systems after renal ischemia-reperfusion injury in rabbits. 1458 61

To ascertain the role of spermidine/spermine N-1-acetyl-transferase (SSAT; the rate-limiting enzyme in polyamine catabolism) in cell injury, cultured kidney (HEK 293) cells conditionally overexpressing SSAT were generated. The SSAT expression was induced and its enzymatic activity increased 24 h after addition of tetracycline and remained elevated over the length of the experiments. Induction of SSAT upregulated the expression of polyamine oxidase and resulted in the reduction of cellular concentration of spermidine and spermine, increased concentration of putrescine, and inhibited cell growth. SSAT overexpression increased the expression of heme oxygenase-1 (HO-1) by 350% 24 h after addition of tetracycline, indicating the induction of oxidative stress. The presence of catalase significantly prevented the upregulation of HO-1 in SSAT overexpressing cells, indicating that generation of H2O2 is partially responsible for the induction of oxidative stress. Overexpression of SSAT caused rounding and loss of cell anchorage and significantly altered the morphology of actin-containing filopodia, suggesting an adhesion defect. SSAT upregulation may mediate majority of the oxidative stress in kidney ischemia-reperfusion injury (IRI) as manifested by decreased cell growth, generation of toxic metabolites (H2O2 and putrescine), upregulation of HO-1, disruption of cell anchorage, and defect in cell adhesion. These data point to the inhibition of polyamine catabolism as a therapeutic approach for the prevention of tissue injury in kidney IRI.
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PMID:Overexpression of SSAT in kidney cells recapitulates various phenotypic aspects of kidney ischemia-reperfusion injury. 1521 72

The aim of the present study was to determine the effects of erdosteine, a new antioxidant and anti-inflammatory agent, on lipid peroxidation, neutrophil infiltration, and antioxidant enzyme activities in a rat model of renal ischemia-reperfusion (I/R) injury. Twenty-eight rats were divided into three groups: sham operation, I/R, and I/R plus erdosteine groups. After the experimental procedure, rats were sacrificed and kidneys were removed and prepared for malondialdehyde (MDA) levels, myeloperoxidase (MPO), xanthine oxidase (XO), catalase (CAT) and superoxide dismutase (SOD) activities. MDA level, MPO and XO activities were significantly increased in the I/R group. On the other hand, SOD and CAT activities were found to be decreased in the I/R group compared to the sham group. Pretreatment with erdosteine significantly diminished tissue MDA level, MPO and XO activities. Our data support a role for erdosteine in attenuation in renal damage after I/R injury of the kidney, in part at least by inhibition of neutrophil sequestration and XO activity.
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PMID:Erdosteine improves oxidative damage in a rat model of renal ischemia-reperfusion injury. 1526 25

Free oxygen radicals and nitric oxide (NO) play a crucial role in the pathogenesis of myoglobinuric acute renal failure (ARF). In this study, we aimed to investigate the effect of melatonin, a potent free radical scavenger, on the myoglobinuric ARF formed by injecting hypertonic glycerol intramuscularly (i.m.). The rats were randomly divided into 4 Groups. Rats in Group 1 were given saline and those in Groups 2, 3, and 4 were injected with glycerol (10 mL/kg) i.m. Concomitant and 24 hours after glycerol injection Group 3 (5 mg/kg) and Group 4 (10 mg/kg) were administrated melatonin intraperitoneally. Forty-eight hours after the glycerol injection, the blood and kidneys of the rats were taken under anesthesia. Kidney morphology and the levels of urea, creatinine and nitric oxide metabolites (NOx) in the plasma and the enzyme activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) and the level of malondialdehyde (MDA) in the kidney were determined. In both groups of melatonin administration, there was no protective effect of melatonin. Moreover, melatonin significantly decreased the level of NO. As a result, we suggest that the decreasing effect of melatonin on NO, which is a strong vasodilatator, may further increase the renal ischemia in this model. Thus, melatonin may have worsening rather than beneficial effects on myoglobinuric ARF.
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PMID:Effects of exogenous melatonin on myoglobinuric acute renal failure in the rats. 1552 5

The effects of proanthocyanidin-rich extract in rats subjected to renal ischemia-reperfusion were examined. Proanthocyanidin-rich extract, which is prepared from grape seeds (Vitis vinifera L.), was given orally at doses of 5 and 10 mg/kg body weight/d for 20 consecutive days prior to ischemia-reperfusion. Administration of proanthocyanidin-rich extract attenuated renal dysfunction, as indicated by serum urea nitrogen and creatinine levels. Additionally, in the ischemic-reperfused kidneys, increased levels of thiobarbituric acid (TBA)-reactive substance and alterations of antioxidant enzyme activities such as superoxide dismutase, catalase and glutathione peroxidase (GSH-Px) were observed. Proanthocyanidin-rich extract-treated groups showed significantly reduced renal TBA-reactive substance levels and enhanced catalase and GSH-Px activities. These results suggest that proanthocyanidin-rich extract has protective effects against ischemia-reperfusion-induced renal damage associated with oxidative stress.
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PMID:Attenuation of renal ischemia-reperfusion injury by proanthocyanidin-rich extract from grape seeds. 1626 3

Reactive oxygen species (ROS) are considered to be important factors involved in the pathophysiology of renal ischemia-reperfusion injury. ROS-induced alterations of proteins, carbohydrates, DNA, and lipid membranes lead to cell and organ dysfunction. Several antioxidant defense mechanisms exist to prevent or limit oxidant injury. Cellular Cu-Zn superoxide dismutase, catalase, and cellular glutathione peroxidase (cGSH-Px) are enzyme ROS scavengers, implicated in the protection against kidney damage resulting from ischemia-reperfusion injury. Reduced glutathione, a cosubstrate of cGSH-Px, have been shown to display a reductive properties without the contribution of enzymes. We examined superoxide anion (O(2)(-)) production by neutrophils, without and with stimulation using opsonized zymosan, in the whole blood of renal transplant patients before and after (5 and 15 minutes) reperfusion. The mean O(2)(-) concentration after reperfusion was statistically significantly higher than that before reperfusion.
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PMID:Superoxide anion as a marker of ischemia-reperfusion injury of the transplanted kidney. 1650 60

Males are much more susceptible to ischemia/reperfusion (I/R)-induced kidney injury when compared with females. Recently we reported that the presence of testosterone, rather than the absence of estrogen, plays a critical role in gender differences in kidney susceptibility to I/R injury in mice. Although reactive oxygen species and antioxidant defenses have been implicated in I/R injury, their roles remain to be defined. Here we report that the orchiectomized animal had significantly less lipid peroxidation and lower hydrogen peroxide levels in the kidney 4 and 24 h after 30 min of bilateral renal ischemia when compared with intact or dihydrotestosterone-treated orchiectomized males. The post-ischemic kidney expression and activity of manganese superoxide dismutase (MnSOD) in orchiectomized mice was much greater than in intact or dihydrotestosterone-administered orchiectomized mice. Four hours after 30 min of bilateral ischemia, superoxide formation was significantly lower in orchiectomized mice than in intact mice. In Madin-Darby canine kidney cells, a kidney epithelial cell line, 1 mm H(2)O(2) decreased MnSOD activity, an effect that was potentiated by pretreatment with dihydrotestosterone. Orchiectomy prevented the post-ischemic decrease of catalase activity. Treatment of male mice with manganese(III) tetrakis(1-methyl-4-pyridyl)porphyrin (MnTMPyP), a SOD mimetic, reduced the post-ischemic increase of plasma creatinine, lipid peroxidation, and tissue hydrogen peroxide. These results suggest that orchiectomy accelerates the post-ischemic activation of MnSOD and reduces reactive oxygen species and lipid peroxidation, resulting in reduced kidney susceptibility to I/R injury.
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PMID:Orchiectomy attenuates post-ischemic oxidative stress and ischemia/reperfusion injury in mice. A role for manganese superoxide dismutase. 1668 13

Ischemia-reperfusion (I/R) injury induces an inflammatory response and production of oxygen-derived reactive species which affect many organs including heart, brain, kidney and gastrointestinal tract. The aim of this study was to assess the hepatic changes after renal I/R injury. Male Sprague Dawley rats were subjected to either sham operation or treatment with L-NAME, L-arginine and BQ-123 during 30 min renal ischemia and 2 h reperfusion injury. Hepatic superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px) activities, and thiobarbituric acid-reactive substances (TBARS) and nitric oxide (NO) levels were evaluated to show hepatic response to renal I/R injury. Catalase and SOD activities showed significant differences between the control and the other groups after I/R. On the other hand, GSH-Px activity did not show any significant changes between the control and the other experimental groups mentioned under above conditions. Meanwhile, levels of TBARS were not different between the control and the other experimental groups, whereas NO level showed changes between the control and experimental groups except the one to which endothelin receptor antagonist agent (BQ-123) subjected. Experimental period may not be enough to determine the changes in GSH-Px activity and level of TBARS. However, catalase and SOD activities decreased in experimental groups treated by chemical agents. NO level decreased in chemicalagent-applied experimental groups but not in the group to which endothelin receptor antagonist BQ-123 was applied alone.
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PMID:Effect of BQ-123 and nitric oxide inhibition on liver in rats after renal ischemia-reperfusion injury. 1691 32


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