Atrazine-Induced Changes in Rodent Hepatic Enzymes and Adrenal Morphology

Abstract

Atrazine (ATR) is one of the most commonly used herbicides worldwide. It is a broad- spectrum herbicide used to control both pre- and post-emergence broadleaf and grassy weeds. ATR’s effects on the hypothalamic-pituitary-gonadal (HPG) axis are the most widely studied, and recent evidence suggests that some of these effects might be mediated by alterations in adrenal gland steroidogenesis and secretion. Furthermore, studies have revealed attenuated effects on the HPG axis after repeated ATR exposure, suggesting an upregulation in the metabolism of atrazine. Our objective was to characterize the effects of ATR exposure on glutathione-s-transferase (GST)-mediated hepatic phase II xenobiotic metabolism components as well as the regulation of hepatic phase I cytochrome P450 (CYP) enzymes. We also examined the effects of ATR on adrenal gland morphology, enzymatic immunoreactivity and expression as well as circulating levels of corticosterone (CORT) and aldosterone. Adult ovariectomized (OVX) rats were gavaged daily with vehicle or various doses of ATR for 1, 2, 3 and 4 or 4, 8 and 14 days. In a subsequent study, rats were treated with vehicle, ATR (100 mg/kg) or restraint stressed, and adrenal morphology and hormone secretions were again examined. Findings indicate that ATR treatment results in increased GST-mediated metabolism and upregulated CYP enzyme expression. Furthermore, ATR leads to changes in adrenal gland morphology, enzyme expression and hormone secretions that mimic the effects of restraint stress.