Hepatotoxic efects of acetaminophen. Protective properties of tryptophan-derivatives

Dremza I.K.1 , Cheshchevik V.T.2, Zabrodskaya S.V.1, Maksimchik Y.Z.1, Sudnikovich E.Ju.1, Lapshina E.A.1, Zavodnik I.B.2

1. Institute of Pharmacology and Biochemistry, National Academy of Sciences of Belarus
2. Institute of Pharmacology and Biochemistry, National Academy of Sciences of Belarus Department of Biochemistry, Yanka Kupala State University
Section: Experimental/Clinical Study
DOI: 10.18097/PBMC20105606710      UDK: 615.099.08+612.354      PubMed Id: 21395073
Year: 2010  Volume: 56  Issue: 6  Pages: 710-718
Rat intoxication with acetaminophen (APAP) (500-1500 mg/kg body weight intragastrically) caused a considerable dose-dependent decrease in reduced glutathione (GSH) level in both liver cellular cytoplasm and mitochondria (at the dose 1500 mg/kg body weight by 60% and 33%, respectively). The cytoplasmic GSH level decreased more pronounced by comparison with that in mitochondria. At the same time, we did not observe any inactivation of the mitochondrial enzymes: succinate dehydrogenase, α-ketoglutarate dehydrogenase, glutathione peroxidase despite of mitochondrial GSH consumption; also we did not observe any decrease in the respiratory activity of liver mitochondria isolated from APAP-intoxicated rats. A tryptophan derivative, melatonin (10 mg/kg body weight), did not prevent intramitochondrial GSH oxidation, but decreased the hepatoxity of APAP, diminishing the activities of AlT and AsT as well as bilirubin level in blood plasma of intoxicated rats. N-acetyl-nitrosotryptophan (a nitric oxide donor) did not exhibit any hepatoprotective effects.
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Dremza I.K., Cheshchevik V.T., Zabrodskaya S.V., Maksimchik Y.Z., Sudnikovich E.Ju., Lapshina E.A., Zavodnik I.B. (2010) Biomeditsinskaya khimiya, 56(6), 710-718.
This paper is also available as the English translation:10.1134/S199075081003008X
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