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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 results in adenosine triphosphate (ATP) depletion, particularly in cells of the proximal tubule (PT), which rely heavily on oxidative phosphorylation for energy supply. Lack of ATP leads to a disturbance in intracellular homeostasis of Na+, K+ and Cl-. Also, cytosolic Ca2+ levels in renal PTs may increase during hypoxia [1], presumably by a combination of impaired extrusion and enhanced influx [2]. However, Ca2+ influx was previously measured using radiolabeled Ca2+ and at varying partial oxygen tension [2]. We have now used to Mn2(+)-induced quenching of fura-2 fluorescence to study Ca2+ influx in individual rat PTs during normoxic and hypoxic superfusion. Normoxic Ca2+ influx was indeed reflected by the Mn2+ quenching of fura-2 fluorescence and this influx could be inhibited by the calcium entry blocker methoxyverapamil (D600; inhibition 50 +/- 2% and 35 +/- 3% for 10 and 100 mumol, respectively). La3+ completely blocked normoxic Ca2+ influx. Hypoxic superfusion or rat PTs did not induce an increase in Ca2+ influx, but reduced this influx to 79 +/- 3% of the normoxic control. We hypothesize that reducing Ca2+ influx during hypoxia provides the cell with a means to prevent cellular Ca2+ overload during ATP-depletion, where Ca2+ extrusion is limited.
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PMID:Hypoxia decreases calcium influx into rat proximal tubules. 950 17

Oxidant injury is considered to be an important mechanism in the pathophysiology of acute renal failure. It has been thought that decrease in extracellular and intracellular fluid and endotoxemia seen in obstructive jaundice may cause an increase in production of oxygen free radicals and impairment in antioxidant defense mechanism. This study is designed to investigate the possible role of oxidant injury in renal failure seen in jaundiced patients. In this study, 28 rats were divided into four groups: Control (C)(N = 7); Renal ischemia (RI)(N = 7); Obstructive jaundice+renal ischemia (OJ+RI)(N = 7); Obstructive jaundice (OJ)(N = 7). All groups were compared with each other according to renal failure findings and enzyme activities, such as Xanthine oxidase (XOD), Superoxide Dismutase (SOD) and Catalase in renal cortex and Glutathione Peroxidase (GSH-Px), in blood at 3rd day after ischemia and reperfusion. Renal failure findings monitored by blood urea and creatinine levels, seemed more evident in OJ+RI than RI group (p < 0.05). When compared with RI, in OJ+RI group, increase in XOD activity at 3rd day was statistically significant [0.259 +/- 0.01 U/g (tissue) and 0.362 +/- 0.03 U/g (tissue) respectively] (p < 0.05). SOD and GSH-Px activities of each ischemic group at 3rd day were decreased compared to non-ischemic groups. This fall was significant (p < 0.05). But there was no statistical difference between jaundiced and non-jaundiced groups. Alterations in catalase activities also had no statistical significance. These findings may suggest that the injury induced by oxygen free radicals at re-oxygenation of tissue after ischemia may also play a role in the pathogenesis of acute renal failure developed in obstructive jaundice.
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PMID:The role of oxygen free radicals in acute renal failure complicating obstructive jaundice: an experimental study. 951 37

This study was undertaken to determine whether reactive oxygen species (ROS) are involved in the pathogenesis of ischemic acute renal failure (IARF) in rabbits. Renal ischemia was induced by clamping bilateral renal arteries for 60 min. Animals were pretreated with combination of xanthine oxidase inhibitor (allopurinol), hydrogen peroxide scavenger (catalase), and hydroxyl radical scavenger (sodium benzoate). Serum creatinine level significantly increased 24 h after ischemia and remained higher to 72 h. Ischemia caused a reduction of GFR and an increase of FENa. Such changes were significantly attenuated by scavenger pretreatment. The uptake of p-aminohippurate in cortical slices and microsomal Na(+)-K(+)-ATPase activity were depressed in kidneys subjected to 72 h of reflow following ischemia, indicating impairment of tubular transport function, which were significantly attenuated by scavenger treatment. Renal blood flow 72 h after reflow was markedly reduced and it was restored by scavenger pretreatment. When animals were pretreated with a potent antioxidant DPPD, lipid peroxidation in cortex and medulla was significantly inhibited. However, ischemia-induced impairment of renal function was not attenuated by pretreatment of the antioxidant. These results suggest that radical scavengers may exert a protective effect against ischemia acute renal failure by other actions rather than ROS scavenging. Thus, the data do not support involvement of ROS in IARF in rabbits.
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PMID:Effects of radical scavengers and antioxidant on ischemic acute renal failure in rabbits. 1004 13

Oxygen metabolites formed during reperfusion of ischemic kidneys prevent recovery of renal function after short periods of renal ischemia. The administration of ATP-MgCl2 is beneficial to the survival of animals after hemorrhagic shock, severe burns, septicemia-peritonitis, post-ischemic hepatic failure, bowel ischemia, and endotoxic shock. In this study, the effect of ATP-MgCl2 on lipid peroxidation and its curative effect were evaluated by measuring the decomposition products of lipid peroxidation, detected as thiobarbituric-acid reactive substances in homogenized kidney tissues in ischemic and reperfused rabbit kidneys. Ischemia was performed by clamping the right renal artery for 60 minutes followed by 30 minutes of reperfusion. Thirty-six rabbits were classified into 6 groups containing 6 rabbits in each. In the first group, no renal ischemia-reperfusion (I-R) was designed (Sham group), the right kidney was removed 90 minutes later. In the second group, I-R was established but nothing given. Saline 0.25 cc/kg was given into the right renal artery in group 3 two minutes before ischemia, and in group 4 two minutes before reperfusion. ATP-MgCl2 17.5 mumol/kg (0.25 cc/kg) was given two minutes before ischemia in group 5, and before reperfusion in group 6. The right kidneys of the rabbits were removed and thiobarbituric-acid reactive substances in the homogenates were measured. In addition, histopathological evaluation was performed. High lipid peroxidation products were recorded in groups 2-5, whereas in group 6, these levels were low similar to those obtained in Sham group (76.72 +/- 1.01 nmol/g tissue). On histopathological evaluation, a considerable cell damage resulting from I-R trauma especially in proximal tubules was observed. In groups which were under saline effect, no histopathological damage was found. Histophatological preservation was better in group 6 rather than in group 5. The results of this study indicate that ATP-MgCl2 is remarkably effective for preventing the lipid peroxidation if given before reperfusion but not before ischemia in experimental I-R injury in rabbit kidneys.
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PMID:The effect of ATP-MgCl2 on lipid peroxidation in ischemic and reperfused rabbit kidney. 1020 3

Renal ischemia injures the renal tubular cell by disrupting the vital cellular metabolic machinery. Further cell damage is caused when the blood flow is restored by oxygen free radicals that are generated from xanthine oxidase. Oxygen radicals cause lipid peroxidation of cell and organelle membranes, disrupting the structural integrity and capacity for cell transport and energy metabolism. In the present study, the possible therapeutic usefulness of the adenosine deaminase inhibitor, 2'-deoxycoformycin (DCF), during renal ischemia and reperfusion injury was investigated. The effects of DCF on renal malondialdehyde (MDA) and ATP levels were studied after 45 min ischemia and 15 min subsequent reperfusion in rat kidneys. MDA levels remained unchanged during ischemia, but increased after the subsequent reperfusion. DCF pretreatment (2.0 mg/kg i.m.) decreased MDA and increased ATP levels during the ischemia-reperfusion period. DCF exerts a dual protective action by facilitating purine salvage for ATP synthesis and inhibiting oxygen radical-induced lipid peroxidation. These results suggest that DCF therapy could be beneficial in the treatment of ischemia-reperfusion renal injuries.
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PMID:The beneficial effect of 2'-deoxycoformycin in renal ischemia-reperfusion is mediated both by preservation of tissue ATP and inhibition of lipid peroxidation. 1043 65

Zinc may have an antioxidant effect mediated by induction of metallothionein. Based on the assumption that metallothionein can scavenge oxygen free radicals, we examined whether zinc administration prior to renal ischemia would improve renal dysfunction caused by ischemia-reperfusion injury in rats. Wistar rats weighing 265 g were treated with an intraperitoneal injection of 20 mg/kg zinc 24 h prior to the renal ischemia-reperfusion procedure, which was achieved by a 30-min clamping of the bilateral renal vessels and subsequent 90-min reperfusion. Thirty-minute renal clearance tests were performed before and after renal ischemia in zinc- (n = 11) and saline-treated (n = 8) rats. Thiobarbituric acid reactive substance, conjugated diene, and metallothionein levels in the renal tissues were also determined. Sham-operated rats (n = 5 in each treatment) served as control for the ischemia-reperfusion rats. Ischemia-reperfusion resulted in significantly lower glomerular filtration rate values and marked increases in tissue concentrations of thiobarbituric acid reactive substance and conjugated diene compared with sham-operation. Zinc administration improved the reduced glomerular filtration rate values seen after the ischemia-reperfusion procedure, but not to the extent of pre-ischemic levels. Zinc pretreatment significantly reduced the increased levels of thiobarbituric acid reactive substance and conjugated diene during ischemia-reperfusion and increased metallothionein levels compared with saline injection. These findings suggest that zinc has an antioxidant effect mediated through the induction of metallothionein, but appears only to have a minor protective effect on renal function induced by renal ischemia-reperfusion injury.
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PMID:Antioxidant effect of zinc on acute renal failure induced by ischemia-reperfusion injury in rats. 1057 93

Renal ischemia as well as oxygen metabolites play an important role in renal injury during myoglobinuric acute renal failure (ARF). On the other hand, flavonoids, a diverse group of constituents naturally occurring in plants, have a strong antioxidative activity, and have been implicated in vascular relaxation. In this study the protective effect of a new bioflavonoid proanthocyanidin-BP1 (BP1), extracted from seeds of grapes, was evaluated in glycerol-induced ARF in rats. Stereological methods were used to quantify changes in renal morphology associated with ARF. Volume density of tubular lumen and intratubular cast formations, nuclear parameters (area, diameter, volume) of epithelial cells in the cortical proximal tubules, and glomerular parameters (surface area, diameter, volume, perimeter) were estimated on kidney sections of rats treated either with 50% glycerol (8 mL/kg i.m.) alone. BP1 (20 mg/kg i.p.) in addition to glycerol, or BP1 alone. It was noted that the volume density of tubular lumen and cast formations were significantly lower (p < 0.001) in kidneys of the rats treated with BP1 in addition to glycerol, compared with those treated with glycerol alone. There were no significant differences in glomerular and nuclear parameters between glycerol treated, and BP1 in addition to glycerol treated rats. Renal function was significantly improved in rats treated with BP1 in addition to glycerol. The results suggest that BP1 is a protective agent in glycerol model of ARF. This effect is probably due to the antioxidative activity of BP1 and reduced toxicity of myoglobin in renal tissue. Moreover, it is possible that the ability of BP1 to protect the kidney is dependent upon renal vascular relaxation. The potential beneficial effects of bioflavonoid-BP1 demonstrated in experimental ARF could be considered in therapy of myoglobinuric ARF.
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PMID:Protective effect of a bioflavonoid proanthocyanidin-BP1 in glycerol-induced acute renal failure in the rat: renal stereological study. 1058 25

Neutrophil migration protects the body against foreign invasion. Sequestration and activation of neutrophils, however, require stringent regulation because they may also cause tissue damage by the release of lysosomal enzymes and reactive oxygen species. The activity of various chemoattractants [e.g., leukotriene B(4) (LTB(4)), interleukin-8, and complements] has been documented by in vitro assays, whereas in vivo data have been limited mostly to histology. To examine in an in vivo model the chemotactic activity and subsequent tissue infiltration and the role of a specific chemoattractant, LTB(4), we used a rat renal ischemia-reperfusion injury model. Fluorescence-labeled Chinese hamster ovary (CHO) cells stably expressing the LTB(4) receptor (CHO-BLT) were able to accumulate along with neutrophils in the postischemic kidney, in contrast to vector control CHO cells. Furthermore, LTB(4) antagonists that protect against the decrease in renal function and diminish the tissue myeloperoxidase activity also led to the marked decrease in the number of CHO-BLT cells and neutrophils. Thus, LTB(4) alone appears sufficient to cause cells to migrate into postischemic tissues, and its dominant role in reperfusion injury has been demonstrated. The utilization of transfectants to pinpoint the role of LTB(4) in these in vivo experiments suggests their potential use with other ligands and/or in other pathological conditions.
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PMID:An in vivo approach showing the chemotactic activity of leukotriene B(4) in acute renal ischemic-reperfusion injury. 1063 64

Picroliv is a potent antioxidant extracted from the roots and rhizome of Picrorhiza kurrooa. It has been shown to impart significant hepatoprotective activities, partly by modulation of free radical-induced lipid peroxidation. Lipid peroxidation and reactive oxygen species are associated with tissue injury in post-ischemic acute renal failure. The efficacy of picroliv was assessed in an in vivo model of renal ischemia-reperfusion injury (IRI) in rats at a dose of 12 mg/kg orally for 7 days. The animals were killed at various times after reperfusion. Increased lipid peroxidation and apoptotic cell number reflected the oxidative damage following renal IRI. Picroliv-pretreated rats exhibited lower lipid peroxidation, improved antioxidant status, and reduced apoptosis, indicating better viability of renal cells. Immunohistochemical studies revealed that picroliv pretreatment attenuated the expression of intercellular adhesion molecule-1 in the glomerular region. These results suggested that picroliv pretreatment protects rat kidneys from IRI, perhaps by modulation of free radical damage and adhesion molecules.
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PMID:Prevention of renal ischemia-reperfusion-induced injury in rats by picroliv. 1073 32

The activation of poly (ADP-ribose) synthetase (PARS) subsequent to DNA damage caused by reactive oxygen or nitrogen species has been implicated in several pathophysiological conditions, including ischemia-reperfusion injury and shock. The aim of this study was to investigate whether PARS inhibitors could provide protection against renal ischemia-reperfusion injury in the rat in vivo. Male Wistar rats were subjected to 45 min bilateral clamping of the renal pedicles, followed by 6 h reperfusion (control animals). Animals were administered the PARS inhibitors 3-aminobenzamide, 1, 5-dihydroxyisoquinoline, or nicotinamide during the reperfusion period. Ischemia, followed by reperfusion, produced significant increases in plasma concentrations of urea, creatinine, and fractional excretion of Na(+) (FE(Na)) and produced a significant reduction in glomerular filtration rate (GFR). However, administration of the PARS inhibitors significantly reduced urea and creatinine concentrations, suggesting improved renal function. The PARS inhibitors also significantly increased GFR and reduced FE(Na), suggesting the recovery of both glomerular and tubular function, respectively, with a more pronounced recovery of tubular function. In kidneys from control animals, histological examination revealed severe renal damage and immunohistochemical localization demonstrated PARS activation in the proximal tubule. Both renal damage and PARS activation were attenuated by administration of PARS inhibitors during reperfusion. Therefore, we propose that PARS activation contributes to renal reperfusion injury and that PARS inhibitors may be beneficial in renal disorders associated with oxidative stress-mediated injury.
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PMID:Inhibitors of poly (ADP-ribose) synthetase reduce renal ischemia-reperfusion injury in the anesthetized rat in vivo. 1074 21


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