Effects of N-acetylcysteine on metabolism, covalent binding, and toxicity of acetaminophen in isolated mouse hepatocytes,☆☆

https://doi.org/10.1016/0041-008X(91)90226-5Get rights and content

Abstract

The effects of N-acetylcysteine (NAC) on the toxicity, conjugate formation, and covalent binding of acetaminophen (pHAA) and its presumed toxic metabolite were studied in suspensions of isolated mouse hepatocytes. Preincubation of liver cells with NAC prior to the addition of pHAA resulted in enhanced protection compared to the concurrent addition of pHAA and NAC, thus indicating a time lag between availability of NAC and exertion of a protective effect. Furthermore, a protective concentration of NAC caused a large increase in the proportion of pHAA plus metabolites found as the glutathione (GSH) conjugate and a decrease in covalent binding of radiolabeled pHAA metabolite to proteins. Thus, it appears that NAC protects against pHAA toxicity by increasing the availability of intracellular GSH.

References (27)

  • G.B. Corcoran et al.

    Inhibition by N-acetylcysteine of acetaminophen covalent binding and liver injury

    Pharmacologist

    (1978)
  • G.B. Corcoran

    Mechanism of Protection against Acetaminophen Induced Hepatic Necrosis by N-Acetylcysteine and Other Sulfhydryl Nucleophiles

  • R.E. Galinsky et al.

    Effect of N-acetylcysteine on the pharmacokinetics of acetaminophen in rats

    Life Sci.

    (1979)
  • Cited by (0)

    Supported by a grant from the Medical Research Council to W.J.R.

    ☆☆

    Presented, in part, at the Canadian Federation of Biological Societies Annual Meeting, St. John's, Newfoundland, June 1980.

    View full text