1. Role of glutathione conjugation in protection of weanling rat liver against acetaminophen-induced hepatotoxicity
- Author
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Emelin Y Vansoun, Afshin Zarghi, and Abdolamir Allameh
- Subjects
Male ,Aging ,medicine.medical_specialty ,Weanling ,Biology ,Acetylcysteine ,chemistry.chemical_compound ,Detoxification ,Internal medicine ,medicine ,Animals ,Acetaminophen ,digestive, oral, and skin physiology ,Glutathione ,Analgesics, Non-Narcotic ,Rats ,Cytosol ,Endocrinology ,Liver ,Biochemistry ,chemistry ,Inactivation, Metabolic ,Toxicity ,Developmental Biology ,medicine.drug ,Conjugate - 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 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.
- Published
- 1997
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