Toxicity of ethacrynic acid in isolated rat hepatocytes

Ethacrynic acid, a loop diuretic drug, caused lipid peroxidation in isolated rat hepatocytes. The thiobarbituric acid reactive substances (TBARS) formation showed a good correlation with the leakage of glutamic–oxaloacetic acid transaminase (GOT) from the hepatocytes. The addition of antioxidants su...

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Bibliographic Details
Published in:Toxicology in vitro 2002-04, Vol.16 (2), p.151-158
Main Authors: Yamamoto, K, Masubuchi, Y, Narimatsu, S, Kobayashi, S, Horie, T
Format: Article
Language:English
Subjects:
Animals
Antioxidants - pharmacology
Aspartate Aminotransferases - metabolism
Biological and medical sciences
Cells, Cultured
Chromatography, High Pressure Liquid
Diuretics - toxicity
Drug Antagonism
Ethacrynic acid
Ethacrynic Acid - toxicity
General aspects. Methods
Glutathione
Hepatocytes - drug effects
Hepatocytes - enzymology
Hepatocytes - pathology
Hepatotoxicity
Lipid Peroxidation
Male
Medical sciences
Phenylenediamines - pharmacology
Proadifen - pharmacology
Promethazine - pharmacology
Protein sulfhydryl
Rats
Rats, Wistar
Sulfhydryl Compounds - analysis
Sulfhydryl Compounds - metabolism
Thiobarbituric Acid Reactive Substances - metabolism
Toxicology
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Summary:Ethacrynic acid, a loop diuretic drug, caused lipid peroxidation in isolated rat hepatocytes. The thiobarbituric acid reactive substances (TBARS) formation showed a good correlation with the leakage of glutamic–oxaloacetic acid transaminase (GOT) from the hepatocytes. The addition of antioxidants such as N, N′-diphenyl- p-phenylenediamine (DPPD) and promethazine to the isolated rat hepatocyte suspension containing ethacrynic acid prevented the lipid peroxidation and decreased the GOT leakage to some extent. SKF-525A inhibited the oxidative metabolism of ethacrynic acid and decreased the TBARS formation, suggesting that the lipid peroxidation was caused by the oxidative metabolim. The intracellular reduced glutathione markedly decreased in the hepatocyte suspension containing ethacrynic acid and the hepatocellular protein sulfhydryls were decreased, which was negatively correlated with the GOT leakage. Thus the ethacrynic acid-induced hepatotoxicity was found to be related to the lipid peroxidation and the decrease of cellular protein sulfhydryls.
ISSN:0887-2333
1879-3177
DOI:10.1016/S0887-2333(01)00107-2