Protection against acetaminophen-induced hepatotoxicity by L-CySSME and its N-acetyl and ethyl ester derivatives

Journal of Biochemical Toxicology
H T NagasawaW B Rathbun

Abstract

We have recently observed that S-(2-hydroxyethylmercapto)-L-cysteine (L-CySSME), the mixed disulfide of L-cysteine and 2-mercaptoethanol, prevented cataracts induced in mice by acetaminophen (ACP) by functioning as a prodrug of L-cysteine and protecting the liver. This prompted the evaluation of the more lipophilic N-acetyl (Ac-CySSME) and ethyl ester (Et-CySSME) derivatives of L-CySSME as proprodrug forms, as well as the "D" enantiomer, as hepatoprotective agents. Serum ALT levels were measured at 24 hours after a toxic but nonlethal dose of ACP that insured 48 hour survival of the animals. Since the increases in ALT produced were highly variable (even after log transformation) and complicated the statistical analyses, we calculated confidence intervals for the mean ALT levels for each treatment group. This enabled comparisons to be made of the efficacy of L-CySSME as well as Ac-CySSME and Et-CySSME with other representative prodrugs of L-cysteine, namely, 2(RS)-methylthiazolidine-4(R)-carboxylic acid (MTCA), L-2-oxothiazolidine-4-carboxylic acid (OTCA), and N-acetyl-L-cysteine (NAC), in protecting the liver. It was shown that L-CySSME and MTCA administered intraperitoneally at 2.5 mmol/kg were superior to the other cysteine p...Continue Reading

Citations

Jan 12, 2007·Journal of Pharmaceutical and Biomedical Analysis·Fabiana S FelixLúcio Angnes
Nov 20, 2002·Journal of Biochemical and Molecular Toxicology·Daune L CrankshawHerbert T Nagasawa
Apr 30, 2003·Journal of Biochemical and Molecular Toxicology·Lorelle I BerkeleyHerbert T Nagasawa

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