ENHANCEMENT OF PARAQUAT TOXICITY BY GLUTATHIONE DEPLETION IN MICE IN VIVO AND IN VITRO

Effect of glutathione (GSH) depletion on paraquat (PQ) toxicity in the liver and kidneys of mice was examined. Glutamic-pyruvate transaminase (GPT) and blood urea nitrogen (BUN) levels in plasma of mice were hardly changed by treatment with 150 μmol/kg of PQ. However, significant increases in the pl...

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Published in:Journal of toxicological sciences 1995/11/25, Vol.20(5), pp.557-564
Main Authors: NAKAGAWA, Ippei, SUZUKI, Mieko, IMURA, Nobumasa, NAGANUMA, Akira
Format: Article
Language:English
Subjects:
Animals
Buthionine sulfoximine
Buthionine Sulfoximine - pharmacology
Cells, Cultured
Deferoxamine - pharmacology
Glutathione - physiology
Lipid Peroxidation
Male
Mice
Paraquat - toxicity
Vitamin E - pharmacology
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Summary:Effect of glutathione (GSH) depletion on paraquat (PQ) toxicity in the liver and kidneys of mice was examined. Glutamic-pyruvate transaminase (GPT) and blood urea nitrogen (BUN) levels in plasma of mice were hardly changed by treatment with 150 μmol/kg of PQ. However, significant increases in the plasma GPT and BUN levels after PQ injection were observed in mice which were pretreated with L-buthionine-SR-sulfoximine (BSO), an inhibitor of GSH synthesis, at 4 hr prior to PQ administration. This result supports the previous observation that hepatotoxicity of PQ was enhanced in diethyl maleate-pretreated mice (Cagen and Gibson, 1977). In the present study, lipid peroxidation evaluated by thiobarbituric acid-reactive substances (TBA-RS) level in the liver of mice given PQ was elevated by pretreatment with BSO. Moreover, enhancement of PQ cytotoxicity by BSO pretreatment was also observed in cultured mouse hepatoma cell line (NCTC clone 1469). Vitamin E, an antioxidant, and Desferal, an iron chelator, significantly prevented mice from the BSO-enhanced hepato-and nephrotoxicity of PQ. These findings suggest that the tissues or cells of low GSH concentration are highly vulnerable to PQ toxicity and GSH may play a major role in diminishing the toxic action of PQ exerted through oxidative stress.
ISSN:0388-1350
1880-3989
DOI:10.2131/jts.20.5_557