Role of glutathione conjugation in protection of weanling rat liver against acetaminophen-induced hepatotoxicity

Abstract

The rate of glutathione (GSH) conjugate formation to acetaminophen (APAP) in livers of weanling and adult rats treated with a single i.p. dose 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 level of liver GSH in weanling rat was 57% of adult level. APAP treatment depleted GSH more significantly in weanling rats as compared to that in adults. N-acetylcystein (NAC) alone had little influence on liver GSH levels. However it was successful in reducing GSH depletion in tissues of growing rats. A 32% repletion in hepatic GSH level in NAC-treated weanling rats was associated with a further 13-fold increase in the rate of GSH conjugate formation. These data together with histopathological results, clearly showed that the inducible GSH system in weanling rat liver act as a safe guard against APAP toxicity. A surge in the rate of APAP-GSH conjugation in growing liver may function in compensation of other detoxification pathways which are saturated more readily at this age.