Investigation of the potential ameliorative effects of DHA-enriched phosphatidylserine on bisphenol A-induced murine nephrotoxicity

In order to investigate the amelioration of docosahexaenoic acid-enriched phosphatidylserine (DHA-PS) on bisphenol A (BPA)-induced nephrotoxicity , the murine nephrotoxicity model was established by intragastric administration of BPA (5 mg/kg/B.W.) for 6 weeks. The biochemical indices, hematoxylin-eosin (H&E) staining, kidney metabolomics, and related protein expression levels of SIRT1-AMPK pathway were then determined. Our results indicated that DHA-PS (100 mg/kg/B.W.) ameliorated the BPA-induced nephrotoxicity after 6 weeks of intragastric administration, primarily by decreasing the serum creatinine (CRE) and blood urea nitrogen (BUN), renal inflammatory cytokines and lipid levels, and increasing the antioxidant enzyme activities . In addition, the untargeted metabolomics of the kidney indicated that BPA perturbed the tryptophan metabolism, pyridine metabolism, and valine , leucine , and isoleucine biosynthesis, while DHA-PS administration significantly affected the glycerophospholipid metabolism, valine, leucine, and isoleucine biosynthesis to ameliorate the BPA-induced metabolic disorder . Moreover, DHA-PS administration could ameliorate the BPA-induced lipid disturbance by upregulating the expressions of AMPKα1, SIRT1, and PPARα while downregulating the expression of SREBP-1c through the SIRT1-AMPK pathway. This is the first time that the amelioration effects of DHA-PS on BPA-induced nephrotoxicity have been investigated from multiple perspectives, suggesting that DHA-PS might be a potential dietary supplement for reducing BPA-induced nephrotoxicity.