Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022672 (acute tubular necrosis)
 2,175 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previously, we have provided evidence that cytochromes P450 (P450s) and flavin-containing monooxygenases (FMOs) are involved in the oxidation of S-(1,2,2-trichlorovinyl)-L-cysteine (TCVC) in rabbit liver microsomes to yield the reactive metabolite TCVC sulfoxide (TCVCS). Because TCVC is a known nephrotoxic metabolite of tetrachloroethylene, the nephrotoxic potential of TCVCS in rats and TCVCS formation in rat liver and kidney microsomes were investigated. At 5 mM TCVC, rat liver microsomes formed TCVCS at a rate nearly 5 times higher than the rate measured with rat kidney microsomes, whereas at 1 mM TCVC only the liver activity was detectable. TCVCS formation in liver and kidney microsomes was dependent upon the presence of NADPH and was inhibited by the addition of methimazole or 1-benzylimidazole, but not superoxide dismutase, catalase, KCN, or deferoxamine, consistent with the involvement of both FMOs and P450s. Rats given TCVCS at 230 micromol/kg i.p. exhibited acute tubular necrosis at 2 and 24 h after treatment, and they had elevated blood urea nitrogen levels at 24 h, whereas TCVC was a much less potent nephrotoxicant than TCVCS. Furthermore, pretreatment with aminooxyacetic acid enhanced TCVC toxicity. In addition, reduced nonprotein thiol concentrations in the kidney were decreased by nearly 50% 2 h after TCVCS treatment compared with saline-treated rats, whereas the equimolar dose of TCVC had no effect on kidney nonprotein thiol status. No significant lesions or changes in nonprotein thiol status were observed in liver with either TCVC or TCVCS. Collectively, the results suggest that TCVCS may play a role in TCVC-induced nephrotoxicity.
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PMID:S-(1,2,2-trichlorovinyl)-L-cysteine sulfoxide, a reactive metabolite of S-(1,2,2-Trichlorovinyl)-L-cysteine formed in rat liver and kidney microsomes, is a potent nephrotoxicant. 1734 24

Intolerance to fava beans in subjects with glucose-6-phosphate-dehydrogenase deficiency (favism) may lead to severe hemolytic crises and decreased renal function. Renal biopsy findings exploring the molecular mechanisms of renal damage in favism have not been previously reported. We report a case of favism-associated acute kidney injury in which renal biopsy showed acute tubular necrosis and massive iron deposits in tubular cells. Interestingly, iron deposit areas were characterized by the presence of oxidative stress markers (NADPH-p22 phox and heme-oxigenase-1) and macrophages expressing the hemoglobin scavenger receptor CD163. In addition, iron deposits, NADPH-p22 phox, hemeoxigenase- 1 and CD163 positive cells were observed in some glomeruli. These results identify both glomerular and tubular involvement in favism-associated acute kidney injury and suggest novel therapeutic targets to prevent or accelerate recovery from acute kidney injury.
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PMID:Molecular mediators of favism-induced acute kidney injury. 2300 41