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

Shireesh Srivastava, Christina Chan

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Abstract

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.

LanguageEnglish (US)
Pages38-49
Number of pages12
JournalFree Radical Research
Volume41
Issue number1
DOIs
StatePublished - Jan 2007

Profile

Palmitates
Cytotoxicity
Hydroxyl Radical
Hydrogen Peroxide
Hepatocellular Carcinoma
Permeability
Nonesterified Fatty Acids
Reactive Oxygen Species
Hepatoblastoma
Ceramides
Toxicology
Oxides
Cyclosporine
Superoxide Dismutase
Nitric Oxide
Fatty Acids
Toxicity
Cell Line
Cells

Keywords

  • Free fatty acids
  • Lipotoxicity
  • Mitochondrial permeability transition
  • Radical scavengers
  • Reactive oxygen species

ASJC Scopus subject areas

  • Biochemistry

Cite this

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