Keap1/Nrf2 pathway in sodium fluoride-induced cardiac toxicity and the prophylactic role of vitamin C versus platelet-rich plasma.

Abstract

The present study was conducted to investigate the role of vitamin C versus platelet-rich plasma (PRP) against sodium fluoride (NaF)-induced cardiotoxicity and cell death in rats' myocardium. Previous studies suggest that NaF decreased cellular viability and intracellular antioxidant power. The present study revealed that NaF administration caused histological alterations in the cardiac muscle and increased the accumulation of intracellular reactive oxygen species, the expression of inducible nitric oxide synthases and proliferating cell nuclear antigen as well as collagen deposition in cardiac tissue. As supported by colorimetric analysis, an elevation in malondialdehyde level and a decrease in both superoxide dismutase (SOD) and thioredoxin-1 oxidoreductase (TrX) levels were seen, whereas molecular analysis revealed a decrease in Keap1 and an increase in Nrf2 and HO-1 gene expression. Pretreatment with vitamin C and PRP prior to NaF administration significantly improved the altered parameters and enhanced the cellular antioxidant capability of myocardium resulting in protection of cardiac muscle from NaF-induced cytotoxicity and apoptotic cell death. The cyto-protective activity of PRP was found to be comparable to that of the known antioxidant, vitamin C.