A comparison of the protective effects of N-acetyl-cysteine and S-carboxymethylcysteine against paracetamol-induced hepatotoxicity.
The protective effect of the sulphur-containing amino acids N-acetyl-cysteine and S-carboxymethylcysteine against paracetamol-induced hepatotoxicity was evaluated in the hamster by biochemical and histological methods. Of the animals receiving paracetamol alone 25% died within 24 h following administration. All surviving animals showed acute hepatocellular injury and marked loss of cytochrome P-450 and hepatic mixed-function oxidase activities. Simultaneous administration of N-acetylcysteine decreased the mortality rate, partly prevented the paracetamol-induced liver damage and partly restored enzyme activities. Simultaneous administration of S-carboxymethylcysteine with paracetamol afforded no protection. Kidneys from all animals were histologically normal. Human liver microsomes and liver microsomes from 3-methylcholanthrene-pretreated hamsters metabolished paracetamol to intermediate(s) that bind covalently to microsomal proteins. The rate of covalent binding was inhibited markedly by N-acetylcysteine and to a lesser extent by S-carboxylmethylcysteine.
D000082:Acetaminophen / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity; D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D002233:Carbocysteine / Q000494:pharmacology*; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology / Q000517:prevention & control*; D006224:Cricetinae; D003545:Cysteine / Q000031:analogs & derivatives*; D006801:Humans; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D008647:Mesocricetus; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D011485:Protein Binding / Q000187:drug effects
D000082:Acetaminophen; D002233:Carbocysteine; D003545:Cysteine; D000111:Acetylcysteine