Work

The metabolism of menadione (2-methyl-1,4-naphthoquinone) by isolated hepatocytes. A study of the implications of oxidative stress in intact cells.

Year: 1982

Type: article

Abstract: The cytotoxic effects of many quinones are thought to be mediated through their one-electron reduction to semiquinone radicals, which subsequently enter redox cycles with molecular oxygen to produce active oxygen species and oxidative stress. The two-electron reduction of quinones to diols, mediated by DT-diaphorase (NAD(P)H: (quinone-acceptor) oxidoreductase), may therefore represent a detoxifying pathway which protects the cell from the formation of these reactive intermediates. By using menadione (2-methyl-1,4-naphthoquinone) and isolated hepatocytes, the relative contribution of the two pathways to quinone metabolism has been studied and a protective role for DT-diaphorase demonstrated. Moreover, in the presence of cytotoxic concentrations of menadione rapid changes in intracellular thiol and Ca2+ homeostasis were observed. These were associated with alterations in the surface structure of the hepatocytes which may be an early indication of cytotoxicity.

Source: Journal of Biological Chemistry

DOI: 10.1016/s0021-9258(18)33730-x

Authors: H Thor, M T Smith, P Hartzell, G Bellomo, S A Jewell, S Orrenius

Institution: Karolinska Institutet

Language: English

Topic: Bioactive Compounds and Antitumor Agents

Subfield: Toxicology

Field: Pharmacology, Toxicology and Pharmaceutics

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,430