MiR-34a/Sirt1/p53 signaling pathway contributes to cadmium-induced nephrotoxicity: A preclinical study in mice

Highlights: • Cadmium induced nephrotoxicity in Kunming mice. • Sirt1 suppression was involved in cadmium-induced nephrotoxicity. • Cadmium exposure increased the levels of acetylation and phosphorylation p53 and miR-34a. • MiR-34a targeted Sirt1 to regulate the cadmium-induced kidney damage. Cadmium (Cd), as an environmental pollutant, can lead to nephrotoxicity. However, its nephrotoxicological mechanisms have not been fully elucidated. In this study, Cd (1.5 mg/kg body weight, gavaged for 4 weeks) was found to induce the renal damage in mice, based on indicators including Cd concentration, kidney index, serum creatinine and blood urea nitrogen levels, pro-inflammatory cytokines and their mRNA expressions, levels of Bcl-2, Bax and caspase9, and histopathological changes of the kidneys. Furthermore, Cd-caused detrimental changes through inducing inflammation and apoptosis via the miR-34a/Sirt1/p53 axis. This is the first report on the role of miR-34a/Sirt1/p53 axis in regulating Cd-caused apoptosis and nephrotoxicity in mice. The findings obtained in this study provide new insights into miRNA-based regulation of heavy metal induced-nephrotoxicity.