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

Abstract

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.

Keywords: Bisphenol A; DHA-Enriched phosphatidylserine; Murine nephrotoxicity; SIRT1-AMPK pathway; glycerophospholipid metabolism.