2-Methyl-thiazolidine-2,4-dicarboxylic acid as prodrug of L-cysteine. Protection against paracetamol hepatotoxicity in mice.
Toxic doses of paracetamol (acetaminophen) destroy the cellular defense system in hepatic tissue. The degree of the destruction can be assessed be measuring the metabolism of sulfhydryl compounds, oxygen radicals and the release of certain enzymes. Administration of 2-methyl-thiazolidine-2,4-dicarboxylic acid (CP; 1.2 mmol/kg) to mice 12 h prior to a toxic dose of paracetamol (600 mg/kg) suppressed the increase of aminotransferase activities in blood serum and the levels of reactive oxygen species in liver tissue. A protective effect of CP was also observed with respect to depletion of non-protein sulfhydryl compounds, cysteine and glycogen. The findings demonstrate that the cysteine prodrug CP is effective in preventing liver damage of a hepatotoxic dose of paracetamol in vivo. A further advantage of the new compound is the long duration of the effect of more than 12 h.
Wlodek
L
L
Institute of Medical Biochemistry, Jagiellonian University, Collegium Medicum, Kraków, Poland.
Rommelspacher
H
H
D000082:Acetaminophen / Q000633:toxicity; D000818:Animals; D000931:Antidotes / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008107:Liver Diseases / Q000188:drug therapy* / Q000378:metabolism; D008111:Liver Function Tests; D008297:Male; D051379:Mice; D018384:Oxidative Stress; D011355:Prodrugs / Q000627:therapeutic use*; D013844:Thiazoles / Q000627:therapeutic use*; D053778:Thiazolidines
D000931:Antidotes; D011355:Prodrugs; D013844:Thiazoles; D053778:Thiazolidines; C014107:2-methyl-2,4-thiazolidine dicarboxylate; D000082:Acetaminophen; D005978:Glutathione