Action of Drugs Affecting the Functioning of the Adrenal Cortex on Adrenal Necrosis Induced by 7,12-Dimethylbenz(a)anthracene and Its 7-Hydroxymethyl Derivative in Rats

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Abstract
Drugs with inhibitory actions on adrenal corticosteroid synthesis were given to young adult female Sprague-Dawley rats prior to the administration of the adrenocorticolytic agents 7,12-dimethylbenz ([alpha])anthracene or its metabolite 7-hydroxymethyl-12-methylbenz([alpha])-anthracene. Adrenal necrosis induced by both polycyclic compounds was prevented by Su 4885 (Metoplrone), Su 9055 [3-(l,2,3,4-tetrahydro-l-oxo-2-naphthyl)-pyrldlne] and Su 10603 [7-chloro-3,4-dlhydro-2-(3-pyridyl)-l (2H)-naphthalenone], but not by Elipten [[alpha]-p-aminophenyl-[alpha]-ethylglutarimlde] and AY 9944 [trans-1,2-bis-(2-chlorobenzylaminomethyl)-cyclohexane dihydro-chloride]. No correlation was found between the reported action of a drug on steroid synthesis and its ability to protect against adrenal necrosis. Pretreatment of rats with ethlonine abolished the protective action of the Su compounds. The mechanism by which these drugs protect the adrenal glands from necrosis is primarily associated with their ability to stimulate drug-metabolizing enzymes in the liver and not with their action upon adrenal corticosteroid synthesis.