Hydrogen peroxide and hydroxyl radicals mediate palmitate-induced cytotoxicity to hepatoma cells: Relation to mitochondrial permeability transition

作者：Srivastava Shireesh; Chan Christina^*

来源：Free Radical Research, 2007, 41(1): 38-49.

DOI：10.1080/10715760600943900

• free fatty acids
• lipotoxicity
• reactive oxygen species
• mitochondrial permeability transition
• radical scavengers

We studied the toxicological responses of a human hepatoblastoma cell line (HepG2/C3A) to various free fatty acids (FFA) in order to identify the relation between reactive oxygen species (ROS) production and mitochondrial permeability transition (MPT). Exposure to the saturated FFA, palmitate, led to a time-dependent ROS production and hydrogen peroxide release as well as a loss of mitochondrial potential. The cytotoxicity of palmitate was significantly reduced by treating with scavengers of hydrogen peroxide, hydroxyl radical and the spin trap alpha-(4-pyridyl-1-oxide)-N-tert-butyl nitrone (POBN). Superoxide dismutase (SOD) mimics, nitric oxide scavenger, and inhibitor of de novo ceramide synthesis had no effect on the toxicity. MPT-inhibitor, cyclosporine, prevented the loss of mitochondrial potential but did not reduce the cytotoxicity. In contrast, inhibiting mitochondrial complexes I and III reduced the early potential loss and the cytotoxicity. These results suggest that palmitate-cytotoxicity to hepatoma cells is mediated through the production of H2O2 and *OH and independent of MPT.

• 出版日期2007-1