TDCPP protects cardiomyocytes from H 2 O 2 -induced injuries via activating PI3K/Akt/GSK3β signaling pathway

Tris (1, 3-dichloro-2-propyl) phosphate (TDCPP) is a major type of organophosphorus flame retardants, and long-term exposure to TDCPP to normal cells or tissues under physiological conditions can induce toxic effects. But how TDCPP leads to the adverse effects is not yet clear, and the effect of TDCPP under pathological conditions such as reactive oxygen species assault is not well understood. The present study aimed to explore the potential effect of TDCPP against H 2 O 2 -induced oxidative stress in H9c2 cardiomyoblasts and rat neonatal cardiomyocytes. We found that H 2 O 2 -treatment decreased cell viability and increased lactate dehydrogenase and malondialdehyde generation of H9c2 cells. However, TDCPP could alleviate these effects. TDCPP alleviated Ca 2+ -overload caused by H 2 O 2 through decreasing store-operated calcium entry. More importantly, TDCPP remarkably decreased H 2 O 2 -induced dephosphorylation of Akt and GSK3β, and through this pathway TDCPP mitigated the H 2 O 2 -induced apoptosis and detrimental autophagy. Collectively, via mitigating Ca 2+ -overload and activating the Akt/GSK3β signaling pathway, TDCPP may have a role in protecting cardiomyocytes from oxidative stress.