Cytoprotective effects of triphlorethol-A against formaldehyde-induced oxidative damage and apoptosis: role of mitochondria-mediated caspase-dependent pathway

J Toxicol Environ Health A. 2010;73(21-22):1477-89. doi: 10.1080/15287394.2010.511564.

Abstract

The toxicity of formaldehyde (HCHO) has been attributed to its ability to form adducts with DNA and proteins. Triphlorethol-A, derived from Ecklonia cava, was reported to exert a cytoprotective effect against oxidative stress damage via an antioxidant mechanism. The aim of this study was to examine the mechanisms underlying the triphlorethol-A ability to protect Chinese hamster lung fibroblast (V79-4) cells against HCHO-induced damage. Triphlorethol-A significantly decreased the HCHO-induced intracellular reactive oxygen species (ROS) production. Triphlorethol-A prevented increased cell damage induced by HCHO via inhibition of mitochondria-mediated caspase-dependent apoptosis pathway. Triphlorethol-A diminished HCHO-induced mitochondrial dysfunction, including loss of mitochondrial membrane action potential (Δψ) and adenosine triphosphate (ATP) depletion. Furthermore, the anti-apoptotic effect of triphlorethol-A was exerted through inhibition of c-Jun NH(2)-terminal kinase (JNK), which was enhanced by HCHO. Our data indicate that triphlorethol-A exerts a cytoprotective effect in V79-4 cells against HCHO-induced oxidative stress by inhibiting the mitochondria-mediated caspase-dependent apoptotic pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects*
  • Caspase 9 / metabolism
  • Cell Line
  • Cell Survival / drug effects
  • Cricetinae
  • Cricetulus
  • Cytoprotection / drug effects
  • DNA Fragmentation
  • Drug Antagonism
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Formaldehyde / toxicity*
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects*
  • Mitochondria / enzymology
  • Oxidative Stress / drug effects*
  • Phaeophyceae / chemistry*
  • Phloroglucinol / analogs & derivatives*
  • Phloroglucinol / pharmacology
  • Plant Extracts / pharmacology
  • Plants, Medicinal

Substances

  • Antioxidants
  • Plant Extracts
  • triphlorethol-A
  • Formaldehyde
  • Adenosine Triphosphate
  • Phloroglucinol
  • Caspase 9