Low-dose bisphenol A plus arsenite: Continuous or intermittent exposures in Sprague-Dawley rats; Effects on kidney oxidative stress, DNA damage, ferroptosis, and fibrosis

Arsenic and bisphenol A (BPA) are widespread environmental pollutants. We have studied the nephrotoxicity of arsenite (ARS), 10 mg/L in drinking water, plus BPA, 50 µg/kg oral dose, in juvenile Sprague-Dawley rats. Animals were randomized into seven groups and exposed to the chemicals either continuously or intermittently, for 8 weeks. The parameters evaluated were urine biomarkers, histopathological and transmission electron microscopic (TEM) examinations, DNA damage (halo assay), and protein expressions. Continuous exposure to AS and BPA significantly increased urinary creatinine, albumin, and total protein, and decreased blood urea nitrogen (BUN). Histopathological and TEM data showed brush border detachment, iron accumulation, podocyte injury, increased slit diaphragm space, and collagen deposition in both exposure groups. Significantly greater DNA damage was seen in the combined-exposure group than in the other experimental groups. Combination exposure in the continuous and intermittent groups showed renal fibrosis and ferroptosis and gene expression analysis revealed a significant increase in Bax and decrease in SIRT 1. Combination exposure was more harmful than the individual exposures in causing kidney injury in these animals.