Comparison of the protective effects of N-acetylcysteine, 2-mercaptopropionylglycine and dithiothreitol against acetaminophen toxicity in mouse hepatocytes

Toxicology
A W Harman, G Self

Abstract

The effects of N-acetylcysteine (NAC), 2-mercaptopropionylglycine (MPG) and dithiothreitol (DTT) on the metabolism and toxicity of acetaminophen (APAP) were examined in isolated mouse hepatocytes maintained in primary culture on collagen-coated dishes. Both NAC and MPG increased the formation of the glutathione and sulfate conjugates of APAP and decreased the covalent binding of the APAP reactive metabolite to cellular protein. DTT did not increase APAP metabolism but did decrease covalent binding. NAC, MPG and DTT decreased plasma membrane damage, as measured by leakage of lactate dehydrogenase from hepatocytes, during a 4-h incubation in 5.0 mM APAP. NAC, MPG and DTT also reduced the APAP-induced fall in glutathione levels in these cells. In other experiments, hepatocytes were exposed to 5.0 mM APAP for 1 h and then incubated during a post-exposure period in APAP-free medium. Damage increased during this post-exposure incubation. Addition of DTT, but not NAC or MPG, after APAP exposure protected the hepatocytes from plasma membrane damage during the post-exposure period. These results indicate that NAC and MPG exert their protective effects by their action on the reactive metabolite of APAP. As well as its effect in reducing ...Continue Reading

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Citations

Dec 1, 1992·Toxicology Letters·A W HarmanS G Shaw
Apr 9, 2002·Clinical Biochemistry·Alpa PopatManuela G Neuman
Sep 1, 2003·Environmental Toxicology and Pharmacology·Chun Kwan WongChong Kim Wong
Nov 7, 2002·Biological & Pharmaceutical Bulletin·Yun-Hee Shon, Kyung-Soo Nam
Dec 11, 2007·Canadian Journal of Physiology and Pharmacology·Manuela G NeumanVanessa Steenkamp
Feb 1, 1997·Drug Metabolism Reviews·S D Cohen, E A Khairallah
Mar 1, 1988·International Journal of Radiation Biology and Related Studies in Physics, Chemistry, and Medicine·H G Claycamp
Apr 1, 2020·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Wenjie WangYa Ding
Feb 24, 2001·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·C ChenJ E Manautou

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