Howard D Colby

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Studies were done to determine the effects of a P450 suicide inhibitor, 1-aminobenzotriazole (ABT), on adrenal steroid and xenobiotic metabolism. Incubation of guinea pig adrenal microsomes with ABT plus an NADPH-generating system caused a time-dependent decline in total P450 concentrations. The maximal decrease in P450 levels was approximately 35% and was(More)
Previous investigations have established that spironolactone (SL) is converted to a reactive metabolite by adrenal microsomal enzymes, resulting in the degradation of cytochrome P-450 (P-450). Deacetylation of SL to 7 alpha-thiospironolactone (7 alpha-thio-SL) is the first step in the activation pathway, but further NADPH-dependent metabolism of 7(More)
Previous studies demonstrated that alpha-tocopherol concentrations were far greater in adrenal glands and in livers from female rats than in those from males. Studies were done to investigate the role of androgens and estrogens in the regulation of adrenal and hepatic alpha-tocopherol content. In males and females, adrenal concentrations of alpha-tocopherol(More)
Previous reports have noted high levels of lipid peroxidation (LP) in vitro in a variety of adrenocortical preparations. However, we have observed that susceptibility to adrenal LP seems to vary considerably from species to species. The current study was done to confirm these apparent species differences in adrenal LP in vitro and to determine if they were(More)
Spironolactone administration (50 mg/kg/day for 3 days) to make guinea pigs decreased cortisol production by adrenal slices in vitro. Adrenal microsomal and mitochondrial cytochrome P-450 levels were also decreased after treatment with spironolactone. The decline in adrenal cytochrome P-450 content was accompanied by decreases in microsomal 21-hydroxylase(More)