EFFECT OF SALICYLATES AND PHENOBARBITAL ON HEPATIC GLUTATHIONE IN THE RAT

  • 1 January 1980
    • journal article
    • research article
    • Vol. 212  (2) , 240-245
Abstract
Phenobarbital and salicylates have opposite effects on hepatic glutathione. Phenobarbital increased glutathione concentration by .apprx. 20-30%. This increase occurred within 48 h and could be attributed almost exclusively to an increase in bound glutathione. No changes in ATP, substrate amino acids for glutathione synthesis or the level of .gamma.-glutamylcysteine synthetase, the rate limiting enzymatic step in glutathione synthesis, were found with phenobarbital. Phenobarbital, which induces hepatic proteins that bind glutathione, increased bound glutathione but did not affect unbound glutathione. The concentration of the latter probably regulates glutathione synthesis. Salicylates (aspirin and sodium salicylate) depleted hepatic glutathione in both saline- and phenobarbital-treated rats. Maximum depletion (.apprx. 40%) was seen 4-6 h after salicylate administration and returned toward the control level by 12 h. The salicylate effect was not related to a change in .gamma.-glutamylcysteine synthetase, .gamma.-glutamyl transpeptidase or the concentrations of free hepatic glycine, glutamate, cysteine and methionine. An increase in concentration of glutathione both in vivo in plasma from salicylate-treated rats and in vitro in buffer from the incubation of liver slices with salicylate suggests that glutathione leakage from hepatocytes is an important factor in salicylate-induced hepatic glutathione depletion.

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