Exposure to low dose of Bisphenol A (BPA) intensifies kidney oxidative stress, inflammatory factors expression and modulates Angiotensin II signaling under hypertensive milieu

Humans are constantly exposed to low concentrations of ubiquitous environmental pollutant, Bisphenol A (BPA). Due to the prevalence of hypertension (one of the major risk factors of cardiovascular disease [CVD]) in the population, it is necessary to explore the adverse effect of BPA under hypertension associated pathogenic milieu. The current study exposed the N omega-nitro-L-arginine methyl ester (L-NAME) induced hypertensive Wistar rats to low dose BPA (50 mu g/kg) for 30 days period. In tissue samples immunohistochemistry, real-time quantitative polymerase chain reaction and enzymatic assays were conducted. Moreover, studies on primary kidney cell culture were employed to explore the impact of low dose of BPA exposure at nanomolar level (20-80 nM range) on renal cells through various fluorescence assays. The observed results illustrate that BPA exposure potentiates/ aggravates hypertension induced tissue abnormalities (renal fibrosis), oxidative stress (ROS generation), elevated angiotensin-converting enzyme activity, malfunction of the antioxidant and tricarboxylic acid cycle enzymes, tissue lipid abnormalities and inflammatory factor expression (both messenger RNA and protein level of TNF-alpha and IL-6). Further, in vitro exposure of nM levels of BPA to primary kidney cells modulates oxidative stress (both superoxide and total ROS), mitochondrial physiology (reduced mitochondrial transmembrane potential-Delta psi m) and lipid peroxidation in a dose dependent manner. In addition, angiotensin II induced ROS generation was aggravated further by BPA during coexposure in kidney cells. Therefore, during risk assessment, a precise investigation on BPA exposure in hypertensive (CVD vulnerable) populations is highly suggested.

Automated summary

This study found that exposure to BPA exacerbates hypertension-induced pathological changes, including renal fibrosis, oxidative stress, elevated angiotensin-converting enzyme activity, dysfunction of antioxidant and tricarboxylic acid cycle enzymes, tissue lipid abnormalities, and expression of inflammatory factors. In addition, high levels of BPA have dose-dependent effects on kidney cells, including oxidative stress, mitochondrial dysfunction, and lipid peroxidation. Therefore, a precise investigation of BPA exposure in hypertensive populations is highly recommended during risk assessment.