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)

We investigated the effects of allopurinol on renal damage following renal ischemia. Male Wistar rats weighing 250-300 g were classified into enflurane and allopurinol groups and anesthetized for 5 minutes using 1.7 MAC of enflurane in 30% oxygen. Then the left renal artery was dissected and clamped. Arterial occlusion was performed under 1.3 MAC enflurane for 30 minutes. Anesthesia was maintained for an additional 90 minutes after releasing the clip. In the allopurinol group, the rats were administered with allopurinol 3 mg.kg-1 intravenously prior to renal ischemia. At the end of anesthesia and 24 hours after the discontinuation of anesthesia, the necrotic areas, kidney weight/body weight ratios, gamma-GTP and NAG activities of the kidney which had been clamped were examined. Urinary gamma-GTP and NAG activities and serum inorganic fluoride concentrations were also measured. The necrotic area was significantly smaller in the allopurinol group than in the enflurane group. The activity of gamma-GTP in the kidney was higher in the allopurinol group than in the enflurane group. The kidney weight/body weight ratio was lower in the allopurinol group than in the enflurane group. There was no difference in serum inorganic fluoride concentration between the allopurinol and enflurane groups. These results suggest that allopurinol decreases renal damage following renal ischemia under enflurane anesthesia.
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PMID:[Effects of allopurinol on renal damage following renal ischemia]. 774 87

Earlier in vitro studies demonstrated the remarkable potency of the lazaroid compounds to prevent oxidant-induced early cell injury. However, the ability of lazaroid compounds to limit oxidative injury in vivo(including renal ischemia-reperfusion) has been less certain, and the early clinical trials using lazaroids to limit CNS injury or organ injury in the setting of transplantation have not been promising. Lazaroid compounds are potent inhibitors of lipid peroxidation, and their inability to influence other key injury processes, particularly during the late stages of cell injury, might partly explain the limited clinical efficacy. To test this, renal tubular (LLC-PK1) cells were incubated with 250 micromH(2)O(2)for 135 min, in the presence or absence of 2-methyl aminochroman (2-MAC, U-83836E), a lazaroid with potent ability to inhibit lipid peroxidation, or desferrioxamine, (DFO) an iron chelator with broader antioxidant efficacy. Cell injury, lipid peroxidation, DNA damage and ATP depletion were measured in the early (immediately after H(2)O(2)incubation) and late (24 h after H(2)O(2)incubation) stages of cell injury. In the early stage, 2-MAC suppressed H(2)O(2)-induced lipid peroxidation and LDH release, but not the DNA damage, ATP depletion or loss of cell replication. In contrast, DFO suppressed all of the measurements. In the late stages, despite continued suppression of lipid peroxidation, only DFO maintained significant cytoprotection against H(2)O(2), and this was accompanied by reduced DNA damage, higher ATP levels and preservation of cell proliferation. Thus, the inability of the lazaroid compound 2-MAC to sustain cytoprotection in the later stages of cell injury might provide at least a partial explanation for the inefficiency of lazaroids to limit tissue injury in clinical and certain in vivo settings.
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PMID:Lazaroid compounds prevent early but not late stages of oxidant-induced cell injury: potential explanation for the lack of efficacy of lazaroids in clinical trials. 1120 66

The complement system is a major component of innate immunity and has been commonly identified as a central element in host defense, clearance of immune complexes, and tissue homeostasis. After ischemia-reperfusion injury (IRI), the complement system is activated by endogenous ligands that trigger proteolytic cleavage of complement components via the classical, lectin and/or alternative pathway. The result is the formation of terminal complement components C3a, C5a, and the membrane attack complex (C5b-9 or MAC), all of which play pivotal roles in the amplification of the inflammatory response, chemotaxis, neutrophil/monocyte recruitment and activation, and direct tubular cell injury. However, recent evidence suggests that complement activity transcends innate host defense and there is increasing data suggesting complement as a regulator in processes such as allo-immunity, stem cell differentiation, tissue repair, and progression to fibrosis. In this review, we discuss recent advances addressing the role of complement as a regulator of IRI and renal fibrosis after organ donation for transplantation. We will also briefly discuss currently approved therapies that target complement activity in kidney ischemia-reperfusion and transplantation.
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PMID:The role of complement in the pathogenesis of renal ischemia-reperfusion injury and fibrosis. 2538 94