Triphenyl phosphate-induced cell injury through endoplasmic reticulum stress in human kidney cells

Triphenyl phosphate (TPhP) is a typical organophosphorus flame retardant (OPFR). Due to its high production and widespread use, exposure to TPhP has been shown to induce nephrotoxicity in animal models. Endoplasmic reticulum (ER) stress is found to be correlated with kidney disease caused by exogenous environmental pollutants. Nevertheless, the connection between ER stress and the nephrotoxic effects caused by TPhP is limited. In this study, human renal tubular epithelial cells (HKC) were chosen to explore the effects of TPhP on cell viability, cell apoptosis, and ER stress. Our study indicated that cell viability was dramatically inhibited in a dose-dependent manner. The half lethal concentration (LC₅₀) value of TPhP after 48 hr exposure is 126.4 µM. A concentration-related Caspase-3 activation and apoptosis occurrence were observed in HKC cells following TPhP treatment. Additionally, the induction of ER stress was demonstrated by the up-regulated expression of ER stress-related genes. To elucidate the role of ER stress in cell damage, sodium 4-phenylbutyrate (4-PBA), an ER stress inhibitor, was used in the co-treatment with TPhP. Results revealed that 4-PBA treatment effectively alleviated TPhP-induced ER stress and cytotoxicity in HKC cells. Taken together, these results indicated that ER stress plays a primary role in TPhP-induced nephrocyte damage and 4-PBA could attenuate these effects.