Vitamin D3 protects against lead-induced testicular toxicity by modulating Nrf2 and NF-κB genes expression in rat

Lead (Pb) is an environmental toxin that has the ability to alter biological processes by inducing oxidative stress (OS) and inflammation. Nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor-kappa B (NF-κB) are two transcriptional factors that participate in the regulation of cellular responses against OS and inflammation. This study was conducted to evaluate the effects of vitamin D3 (VD) on the prevention of testicular damages of Pb and its association with Nrf2 and NF-κB gene expression levels and their downstream molecules. Forty male Wistar rats were divided into four groups and treatments were performed as following for four weeks: control group received no treatment, VD group were injected intramuscularly with 1000 IU of VD/Kg every other day, Pb group received 1000 mg of Pb/L of drinking water, and Pb + VD group were exposed to Pb and VD simultaneously. The results demonstrated significant decrease in the levels of tissue antioxidants, and increase in inflammatory cytokines in the Pb-intoxicated group, with increased Nrf2 and NF-κB mRNA levels. A remarkable reduction in sperm criteria and a significant disruption in serum hormones were also observed. Anyhow, VD supplementation during exposure to Pb showed a significant protective effect against all pathophysiologic alterations caused by Pb. Furthermore, VD affected the expression of Nrf2 and NF-κB and mitigated the harsh effects of Pb. In conclusion, our findings indicate that VD attenuated the toxic impacts of Pb on testis through modulation of Nrf2 and NF-κB gene expression levels which further regulated the OS and inflammatory responses.