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.

Protective Effect of Vitamin D3 Against Pb-Induced Neurotoxicity by Regulating the Nrf2 and NF-κB Pathways.

Lead (Pb) is a known toxic heavy metal which accumulates in different tissues and causes oxidative stress (OS) and inflammation. The brain tissue is considered as one of the most vulnerable organs to the Pb-induced toxicity. The aim of this study was to investigate the therapeutic effects of vitamin D3 (VD) supplementation against the damages caused by chronic Pb toxicity in the cerebral cortex. Forty Wistar rats were divided into four equal groups and were treated as follows: control group received no treatment, VD group received 1000 IU/kg of VD by intramuscular injection every other day, Pb group received 1000 mg/L of Pb in drinking water, and Pb + VD group received VD and Pb simultaneously. The experiment lasted for 4 weeks and the analyses were conducted 24 h after the last administrations. The obtained results demonstrated that Pb significantly increased cortical lipid peroxidation and reactive oxygen species (ROS) levels. At the same time, there was a significant reduction in glutathione (GSH) content, catalase (CAT), and superoxide dismutase (SOD) activities, as well as a significant increase in the tissue level of inflammatory cytokines. Furthermore, Pb increased the messenger RNA (mRNA) expression level of nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor-kappa B (NF-κB). Anyhow, VD administration during the period of Pb exposure suppressed the OS and inflammation by increasing the antioxidant molecules and decreasing the inflammatory cytokines and consequently repaired Pb-induced cortical tissue damages. Remarkably, these responses were concomitant with the alterations in Nrf2 and NF-κB gene expressions. In conclusion, the present study discloses the potential protective effects for VD against Pb-induced neurotoxicity via anti-inflammatory and antioxidative mechanisms.