Quinone toxicity in hepatocytes without oxidative stress

doi:10.1016/0003-9861(86)90047-0

Archives of Biochemistry and Biophysics

Volume 251, Issue 1, 15 November 1986, Pages 25-35

https://doi.org/10.1016/0003-9861(86)90047-0 Get rights and content

Abstract

The toxicity of quinones is believed to be mediated via redox cycling involving formation of semiquinone radicals which autoxidize to form active oxygen species. However, when the cytotoxicity of benzoquinones was compared using freshly isolated rat hepatocytes, benzoquinones which did not mediate oxidative stress were highly toxic. Thus, the benzoquinone analogs in decreasing order of cytotoxicity were 2-CH₃-, 2-Br-, unsubstituted, 2,6-(CH₃)₂-, 2,5-(CH₃)₂-, and 2,3,5-(CH₃)₃-benzoquinone. Cellular thiols were rapidly depleted and glutathione (GSH) was converted to a quinone conjugate without oxidation to glutathione disulfide. No increase in cyanide-resistant respiration was observed and benzoquinone-induced cytotoxicity was not enhanced by inactivation of catalase or glutathione reductase. In contrast, duroquinone [2,3,5,6-(CH₃)₄-benzoquinone], which stimulated cyanide-resistant respiration and GSH oxidation, was only cytotoxic when catalase or glutathione reductase was inactivated. These results suggest that alkylation and/or oxidative stress may be important mechanisms in the cytotoxicity of benzoquinone derivatives.

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¹: Permanent address: Department of Biology, 2nd University of Rome “Tor Vergata”, I-00173 Rome, Italy.

³: Permanent address: Department of Biochemistry, Memorial University of Newfoundland, St. John's, Newfoundland, Canada A1B 3X9.

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Quinone toxicity in hepatocytes without oxidative stress

Abstract

J. Biol. Chem

Arch. Biochem. Biophys

Arch. Biochem. Biophys

J. Biol. Chem

J. Biol. Chem

J. Biol. Chem

Anal. Biochem

Anal. Biochem

Chem. Biol. Interact

Chem. Biol. Interact

J. Biol. Chem

Chem. Biol. Interact

J. Biol. Chem

Arch. Biochem. Biophys

Arch. Biochem. Biophys

Biochim. Biophys. Acta

Arch. Biochem. Biophys

Biochem. Biophys. Res. Commun

Biochim. Biophys. Acta

FEBS Lett