Protective role of melatonin on Bisphenol A-induced Adrenal Gland dysfunction in pubertal Wistar rats exposed in-utero

BPA-induced adrenal dysfunction

Abstract

Most studies on the effect of Bisphenol A (BPA) on the endocrine organs are either not environmentally relevant due to high doses of BPA exposure or involve direct exposure to adult rats.  To bridge this knowledge gap, this present study was designed to investigate the protective effects of melatonin (MLT) on adrenal gland dysfunction in pubertal male Wistar rats exposed to environmentally relevant doses of BPA in utero. Pregnant Wistar rats were randomly assigned into five groups (n=5): Group 1 (control) received 0.2 ml 1% dimethyl sulfoxide (DMSO)/99% canola oil as the vehicle; Group 2 received BPA at 50 µg/kg/day; Group 3 received BPA at 150 µg/kg/day; Group 4 received BPA at 50 µg/kg/day with concurrent MLT 1 mg/kg/day; and Group 5 received BPA at 150 µg/kg/day with concurrent MLT 1 mg/kg/day.  All treatments were administered by gavage from gestational day (GD) 10-21. Thereafter, two male offspring randomly from each litter per group (n=10) were weighed, and blood samples were collected for serum hormonal assay before they were euthanized on post-natal day (PND) 42. Biomarkers for oxidative stress (MDA, H₂O₂) and antioxidants (GPx and GST) were estimated. The levels of corticosterone and ACTH were determined using ELISA kits. Histopathology and histomorphometry of the gland were carried out using standard methods. BPA exposure induced marked dose-dependent adrenal alterations, including changes in body and organ weights, alterations in serum hormone levels, decreased activities of antioxidant enzymes while increased ROS and MDA as well as the induction of adrenal lesions. However, melatonin co-administered with BPA protected against BPA-induced alterations of adrenal function. Hence, melatonin protects against BPA-induced toxicity of the adrenal gland of pubertal male rats exposed in utero.