Role of glutathione conjugation in protection of weanling rat liver against acetaminophen-induced hepatotoxicity.
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 rate of conjugation in weanling rat is 24-times greater than that of adults. Increased rate of GSH conjugation was independent of 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.
Allameh
A
A
Department of Biochemistry, Faculty of Medical Sciences, Tarbiat Modaress University, Tehran, Iran.
Vansoun
E Y
EY
Zarghi
A
A
D000082:Acetaminophen / Q000378:metabolism* / Q000493:pharmacokinetics / Q000633:toxicity*; D000111:Acetylcysteine / Q000494:pharmacology; D000375:Aging / Q000378:metabolism; D018712:Analgesics, Non-Narcotic / Q000378:metabolism* / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D005978:Glutathione / Q000378:metabolism*; D008658:Inactivation, Metabolic; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051381:Rats
D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen; D005978:Glutathione; D000111:Acetylcysteine