Kinetic studies of aflatoxin B1-glutathione conjugate formation in liver and kidneys of adult and weanling rats

Aflatoxin B1(AFB1)-glutathione(GSH) conjugation is the major pathway for th e detoxification of aflatoxin metabolites. This reaction is catalysed by GS H S-transferase (GST) and play a major role in modulation of AFB1 adduct fo rmation to nuclear DNA. Changes recorded in hepatic GST activity during dev elopment of rats can alter the balance between AFB1-GSH conjugation and AFB 1-DNA adduct formation. Measurment of cytosolic GST using 1-chloro-2,4-dini trobenzene (CDNB) as the substrate showed that the enzyme activity is initi ally lower in weanling tissues as compared to that of adults. But neverthel ess hepatic and renal cytosolic GST activity is increased significantly in growing rats pretreated with AFB1. Kinetic studies of AFB1-GSH conjugate fo rmation in kidneys and livers of the two-age groups of rats treated with a single i.p. dose of AFB1 (400 mu g/kg b.w.) revealed that at the end of 24 h of AFB1 administration the rate of the conjugate formation in kidneys of immature rats was approximately twice of that measured in adults. Age-relat ed differences in the GST activity as well as AFB1-GSH conjugation was more pronounced in kidneys. The conjugate formation in kidneys of growing rats during 6-24 h following AFB1 administration shows that urinary excretion of aflatoxin metabolites is relatively rapid in growing rats. The major porti on of the AFB1-GSH is formed in liver but contribution of the renal tissue to the formation of detoxification metabolites can not be ruled out. These data demonstrate that aflatoxin metabolites are eliminated more efficiently from kidneys of a growing rat. AFB1-induced GST induction in renal tissues of growing animals during 24 h of the carcinogen administration could be c onsidered as an important mechanism for GSH conjugate formation and aflatox in detoxification. Therefore GST induction in response to hepatotoxic drugs can confer resistance to young animals being exposed for the first time to such drugs. It is also worthmentioning that the GST activity measured befo re AFB1 administration does not reflect the rate of AFB1 detoxification via GSH conjugation. (C) 2000 Published by Elsevier Science Ireland Ltd. AII r ights reserved.