ROLE OF GLUTATHIONE CONJUGATION IN PROTECTION OF WEANLING RAT-LIVER AGAINST ACETAMINOPHEN-INDUCED HEPATOTOXICITY

The rate of glutathione (GSH) conjugate formation to acetaminophen (AP AP) in livers of weanling and adult rats treated with a single i.p. do se of APAP was compared. HPLC analysis of cytosolic fractions revealed that the rate of conjugation in weanling rat is 24-times greater than that of adults. Increased rate of GSH conjugation was independent of the age-related difference observed in liver GSH content. The normal l evel of liver GSH in weanling rat was 57% of adult level. APAP treatme nt depleted GSH more significantly in weanling rats as compared to tha t in adults. N-acetylcystein (NAC) alone had little influence on liver GSH levels. However it was successful in reducing GSH depletion in ti ssues of growing rats. A 32% repletion in hepatic GSH level in NAC-tre ated weanling rats was associated with a further 13-fold increase in t he rate of GSH conjugate formation. These data together with histopath ological results, clearly showed that the inducible GSH system in wean ling rat liver act as a safe guard against APAP toxicity. A surge in t he rate of APAP-GSH conjugation in growing liver may function in compe nsation of other detoxification pathways which are saturated more read ily at this age. (C) 1997 Elsevier Science Ireland Ltd.