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)

Reactive oxygen species (ROS) have been implicated in the pathophysiology of renal ischemia/reperfusion injury. Endothelin-1 (ET-1) is generated in abundance in renal ischemia/reperfusion with resultant decreases in renal blood flow and glomerular filtration rate. To determine if ROS regulate ET-1 production, the effect of ROS donors or scavengers on ET-1 protein and mRNA levels in cultured human mesangial cells was examined. Incubation with xanthine/xanthine oxidase, glucose oxidase, or H2O2 caused a dose-dependent rise in ET-1 release. Similarly, xanthine/xanthine oxidase or H2O2 augmented ET-1 mRNA levels. In contrast, the ROS scavengers dimethylthiourea (DMTU), dimethylpyrroline N-oxide, or pyrrolidine dithiocarbamate reduced basal ET-1 release, while DMTU lowered ET-1 mRNA levels. Deferoxamine, an iron chelator, also decreased basal ET-1 release. Superoxide dismutase potentiated the ET-1 stimulatory effect of xanthine/xanthine oxidase, while catalase abrogated the effect of xanthine/xanthine oxidase and H2O2. The effects of ROS were unrelated to changes in nitric oxide production or cytotoxicity. These data indicate that exogenously or endogenously-derived ROS can increase ET-1 production by human mesangial cells. While superoxide anion reduces ET-1 levels, H2O2 leads to enhanced production of the peptide. ROS stimulation of mesangial cell ET-1 production may contribute to impaired glomerular hemodynamics in the setting of renal ischemia/reperfusion injury.
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PMID:Effect of reactive oxygen species on endothelin-1 production by human mesangial cells. 877 Sep 66

Dithiocarbamates can modulate the expression of genes associated with inflammation or development of ischemia/reperfusion injury. Here, we investigate the effects of pyrrolidine dithiocarbamate, an inhibitor of nuclear factor (NF)-kappaB activation, on the renal dysfunction and injury caused by ischemia/reperfusion of the rat kidney. Bilateral clamping of renal pedicles (45 min) followed by reperfusion (6 h) caused significant renal dysfunction and marked renal injury. Pyrrolidine dithiocarbamate (100 mg/kg, administered i.v.) significantly reduced biochemical and histological evidence of renal dysfunction and injury caused by ischemia/reperfusion of the rat kidney. Furthermore, pyrrolidine dithiocarbamate markedly reduced the expression of inducible nitric oxide synthase (iNOS) protein and significantly reduced serum levels of nitric oxide. Finally, pyrrolidine dithiocarbamate inhibited the activation of NF-kappaB by preventing its translocation from the cytoplasm into the nuclei of renal cells. These results demonstrate that pyrrolidine dithiocarbamate reduces renal ischemia/reperfusion injury and that dithiocarbamates may provide beneficial actions against ischemic acute renal failure.
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PMID:Pyrrolidine dithiocarbamate reduces renal dysfunction and injury caused by ischemia/reperfusion of the rat kidney. 1466 32

Despite the causative role of oxidative stress in renal ischemia-reperfusion (I-R) injury effects of preservation solutions on reactive oxygen species (ROS) release have not been sufficiently evaluated. We compared the effects of most common solutions in kidney transplantation, University of Wisconsin (UW) and Histidine-Tryptophan-Ketoglutarate (HTK). ROS formation in isolated perfused rat kidney was detected by electron spin resonance spectroscopy using spin label 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine. Donor kidneys from Lewis rats were pretreated with saline (controls), in therapeutic groups, kidneys underwent 18 h of cold storage (CS) preserved by HTK or UW solution. Experimental protocol included a stabilization period followed by additional I-R. Kidneys preserved by HTK produced highest ROS values in the control period after CS, whereas levels in UW and control group did not vary significantly. A peak release induced by additional I-R was also significantly highest in HTK kidneys, and UW did not differ from controls. During reperfusion, levels in HTK exceeded control and UW values. Renal vascular resistance, caspase-3-activity, and tissue hydration were enhanced in HTK compared with UW group, whereas ATP concentration was less reduced in UW-preserved tissue. These data show the greater antioxidative potential of UW solution, which also attenuated organ impairment after CS in the early reperfusion period.
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PMID:Evaluation of preservation solutions by ESR-spectroscopy: superior effects of University of Wisconsin over Histidine-Tryptophan-Ketoglutarate in reducing renal reactive oxygen species. 1731 Oct 72