Tetrahydrocurcumin protection against doxorubicin-induced apoptosis

Tetrahydrocurcumin (THC), an active metabolite of curcumin, possesses potent antioxidant activity and is more stable in vivo than curcumin. We investigated the protective effect of THC on doxorubicin (DOX)-induced apoptotic cell death in association with the dissipation of the mitochondrial membrane potential using cholangiocyte MMNK-1 cell lines. Exposure to DOX (0.3-3 M for 24 h) induced cell death in a dose-dependent manner. Pre-treatment with THC (1, 3, 6 M) for 24 h significantly increased cell survival. To determine the THC cytoprotective mechanism, intracellular superoxide anion levels and mitochondrial transmembrane potential were measured. Exposure to DOX increased intracellular superoxide anions in the cells. The superoxide levels were significantly reduced when the cells were pretreated with THC, implying the presence of antioxidant activity in THC. Moreover, DOX-induced dissipation of the mitochondrial membrane potential was alleviated by pre-treatment with THC. The results suggest that THC induces a cytoprotective effect that maintains mitochondrial function and suppresses the formation of reactive-oxygen species.