The Journal of Toxicological Sciences
Online ISSN : 1880-3989
Print ISSN : 0388-1350
ISSN-L : 0388-1350
ENHANCEMENT OF PARAQUAT TOXICITY BY GLUTATHIONE DEPLETION IN MICE IN VIVO AND IN VITRO
Ippei NAKAGAWAMieko SUZUKINobumasa IMURAAkira NAGANUMA
Author information
JOURNALS FREE ACCESS

1995 Volume 20 Issue 5 Pages 557-564

Details
Abstract

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.

Information related to the author
© The Japanese Society of Toxicology Headquarters
Next article
feedback
Top