Protective Effects of Grape Seed Procyanidin Extract on Fluoride-Induced nephrotoxicity and the possible role of Nrf2 signaling pathway

To investigate effects of fluoride-induced renal damage and possible role of the Nrf2 signaling pathway and explore the protective activity of Grape Seed Procyanidin Extract (GSPE). A fluoride-exposed rat model was established through drinking water. Oxidative stress parameters and serum markers that reflect renal function were analyzed. Pathological changes were assessed using HE and TUNEL methods. Nrf2 signaling pathway-related and apoptosis-related cleaved Caspase-3 proteins were detected by Western blot. Fluoride exposure caused a significant increase in serum markers of renal function, renal histopathological alterations, oxidative stress, and apoptosis. The protein expression levels of Nrf2, HO-1, and NQO-1 along the Nrf2 signaling pathway were depressed, while the cleaved Caspase-3 protein were upregulated after fluoride exposure. HE and TUNEL examination showed that the renal tissue of fluoride rats was repaired by GSPE. The level of MDA was decreased; while the level of GSH, activities of CAT, and SOD of the kidney were promoted by GSPE. Decreased serum markers such as BUN, UA, and Cr indicate a marked improvement in renal function. GSPE therapy up-regulated the expression levels of Nrf2, HO-1, NQO-1 and down-regulated cleaved Caspase-3 proteins in the kidney. Supplementary GSPE with fluoride significantly alleviated its nephrotoxicity. The results above mentioned indicated that fluoride induced nephrotoxicity possibly through activate the Nrf2 signaling pathway and the presence of GSPE mitigate its nephrotoxicity.