title: The ameliorative effects of L-2-oxothiazolidine-4-carboxylate on acetaminophen-induced hepatotoxicity in mice.
abstract: The aim of the study was to investigate the ameliorative effects and the mechanism of action of L-2-oxothiazolidine-4-carboxylate (OTC) on acetaminophen (APAP)-induced hepatotoxicity in mice. Mice were randomly divided into six groups: normal control group, APAP only treated group, APAP + 25 mg/kg OTC, APAP + 50 mg/kg OTC, APAP + 100 mg/kg OTC, and APAP + 100 mg/kg N-acetylcysteine (NAC) as a reference control group. OTC treatment significantly reduced serum alanine aminotransferase and aspartate aminotransferase levels in a dose dependent manner. OTC treatment was markedly increased glutathione (GSH) production and glutathione peroxidase (GSH-px) activity in a dose dependent manner. The contents of malondialdehyde and 4-hydroxynonenal in liver tissues were significantly decreased by administration of OTC and the inhibitory effect of OTC was similar to that of NAC. Moreover, OTC treatment on APAP-induced hepatotoxicity significantly reduced the formation of nitrotyrosin and terminal deoxynucleotidyl transferase dUTP nick end labeling positive areas of liver tissues in a dose dependent manner. Furthermore, the activity of caspase-3 in liver tissues was reduced by administration of OTC in a dose dependent manner. The ameliorative effects of OTC on APAP-induced liver damage in mice was similar to that of NAC. These results suggest that OTC has ameliorative effects on APAP-induced hepatotoxicity in mice through anti-oxidative stress and anti-apoptotic processes.
authors.affiliation: Department of Radiological Sciences, Jeonju University, Jeonju 560-759, Korea. jwchoi@jj.ac.kr
authors.forename: Jiwon
authors.initials: J
authors.lastname: Choi
authors.forename: Kwang-Hyun
authors.initials: KH
authors.lastname: Park
authors.forename: Sung Zoo
authors.initials: SZ
authors.lastname: Kim
authors.forename: Jun Ho
authors.initials: JH
authors.lastname: Shin
authors.forename: Seon-Il
authors.initials: SI
authors.lastname: Jang
mesh_terms: D000082:Acetaminophen / Q000633:toxicity*; D000410:Alanine Transaminase / Q000097:blood; D000447:Aldehydes / Q000378:metabolism; D018712:Analgesics, Non-Narcotic / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D053148:Caspase 3 / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000517:prevention & control*; D053938:DNA Fragmentation; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009336:Necrosis / Q000139:chemically induced / Q000517:prevention & control; D018384:Oxidative Stress / Q000187:drug effects; D011761:Pyrrolidonecarboxylic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D053778:Thiazolidines / Q000494:pharmacology* / Q000627:therapeutic use; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D000447:Aldehydes; D018712:Analgesics, Non-Narcotic; D000975:Antioxidants; D053778:Thiazolidines; C002744:3-nitrotyrosine; D000082:Acetaminophen; D014443:Tyrosine; D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C505409:Casp3 protein, mouse; D053148:Caspase 3; D005978:Glutathione; C027576:4-hydroxy-2-nonenal; D011761:Pyrrolidonecarboxylic Acid; C029536:2-oxothiazolidine-4-carboxylic acid