SAT-710 Comparative Histopathology of Endocrine Glands in Phthalate Exposed Male Wistar Rats Unveil the Vulnerability of Adrenal Gland and Augmented by Molecular Docking

Abstract

Limited research has been conducted on adrenal gland as a target of endocrine-disrupting chemicals (EDCs). Moreover, studies on steroidogenesis as the target of EDCs has also attracted lesser attention compared to other metabolic pathways. We studied the effects of two extensively used phthalate esters viz., di-ethyl hexyl phthalate (DEHP) and di-butyl phthalate (DBP) on the adrenal gland in Wistar rats and checked its susceptibility against the exposure of these extensively used phthalates categorized as EDCs. Male rats were divided into seven groups (n = 6). Group I (control) received only corn oil (as a vehicle). Group II, III and IV were treated daily with DEHP at the dose of 250, 750 and 1500 mg/kg-BW respectively per os for 14 days. Group V, VI and VII were treated with a daily dose of DBP 100, 500 and 1000 mg/kg-BW respectively per os for 14 days. The comparative histological observation of endocrine glands i.e., pituitary, pineal, thyroid, parathyroid, adrenal gland and testes unveil that changes in adrenal gland towards the DEHP and DBP were more remarkable compared to other endocrine glands. Glucocorticoid biosynthesis pathway in the adrenal gland was analyzed by molecular docking of DEHP and DBP with the enzyme proteins involved in the pathway using Maestro Schrodinger 9.4 software. It showed the potential of DEHP and DBP to inhibit these proteins comparable to the known inhibitors of enzymes involved. The present study used a novel approach of in silico and in vivo to elucidate the sensitivity of adrenal gland towards EDCs through the analysis of the sensitivity of adrenal steroidogenesis on exposure to two widely distributed phthalates with environmental and human health risk potential.