Subchronic exposure to fluoride and arsenite induces oxidative stress and activates the Nrf2 signaling pathway in the kidneys of rat offspring

Underground drinking water is commonly contaminated with arsenite (As) and fluoride (F) associated with chronic kidney diseases in humans; however, the combined renal toxicity of these pollutants and the underlying mechanisms are still unclear. The aim of the present study was to investigate the interaction between F and As regarding toxic effects on the kidney of rat offspring exposed to pollutants during prenatal and postnatal development. Pregnant rats were randomly divided into four groups that received NaF (100 mg/L), NaAsO2 (50 mg/L), NaF (100 mg/L) and NaAsO2 (50 mg/L) in drinking water, or clean water, respectively, during gestation and lactation. After weaning, six male pups were randomly selected from each group and continued on the same treatment as their mothers for up to three months. The results revealed that subchronic exposure to high-dose F and/or As decreased the organ coefficient of the kidneys and disrupted kidney ultrastructure; moreover inhibited the activity of antioxidant enzymes and increased the generation of malondialdehyde in the kidney. Furthermore, As and/or F increased mRNA and protein expression of nuclear factor erythroid 2-related factor-2 (Nrf2) and its downstream targets (Ho-1, Gclc, and Nqo1) involved in the regulation of oxidative stress. These results suggest that renal toxicity of F and As is associated with the induction of mitochondrial damage and oxidative stress, and the Nrf2 pathway is involved in the process, moreover, F may counteract the effect of As when the toxicants were used in combination.