Effect of Experimental Kidney Disease on the Functional Expression of Hepatic Reductases
作者： Osama Y. Alshogran , Judith Naud , Andrew J. Ocque , François A. Leblond , Vincent Pichette
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摘要: Chronic kidney disease (CKD) affects the nonrenal clearance of drugs by modulating functional expression hepatic drug–metabolizing enzymes and transporters. The impact CKD on oxidative conjugative metabolism has been extensively studied. However, its effect drug reduction, an important phase I drug–metabolism pathway, not investigated. We aimed to assess experimental reduction using warfarin as a pharmacological probe substrate. Cytosolic microsomal cellular fractions were isolated from liver tissue harvested five-sixths-nephrectomized control rats (n = 10 per group). enzyme kinetics for evaluated in both fractions, formation alcohols was used indicator reductase activity. Selective inhibitors employed identify reductases involved reduction. Gene protein determined quantitative real-time polymerase chain reaction Western blotting, respectively. Formation RS/SR-warfarin alcohol decreased 39% (P 30%
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