Triphenyl phosphate exposure induces kidney structural damage and gut microbiota disorders in mice under different diets

Abstract

Exposure of humans to organophosphate flame retardants (OPFRs) and the consequent health risk have increased owing to the latter's widespread application. Although triphenyl phosphate (TPP), an OPFR, is a potential chemical determinant of liver function damage, its effects on kidney function in mice under high fructose/fat (HFF) diet are still unclear. In this study, C57BL/6J mice were fed HFF to generate an obesity model and mice were exposed to low dose (0.01 mg/kg/day; TPP-L) and high dose (1 mg/kg/day; TPP-H) of TPP for 12 weeks. Results showed that TPP-L and TPP-H combined with HFF, as well as TPP-H alone, caused kidney structural damage and gut microbiota disorders in mice. Inflammatory response induced by nuclear factor kappa B (NF-κB p65)/nod-like receptor protein 3 (NLRP3) and caspase-3 promoted kidney structure damage, as well as accumulation of triglyceride and total cholesterol and the protein residues in urine. Although TPP-L did not cause obvious structural damage in the kidneys, 0.01 mg/kg TPP induced significant inflammation and gut microbiota disorders. These findings provide new insights regarding health risk assessment after chronic exposure to TPP and HFF alone, as well as a combination of TPP with HFF in mice.