Hepatotoxic effects of acetaminophen. Protective properties of tryptophan derivatives

• Published in: Biochemistry (Moscow). Supplement. Series B, Biomedical chemistry Vol. 4; no. 3; pp. 264 - 268
• Main Authors: Dremza, I. K., Cheshchevik, V. T., Zabrodskaya, S. V., Maksimchik, Yu. Z., Sudnikovich, E. Yu, Lapshina, E. A., Zavodnik, I. B.
• Format: Journal Article
• Language: English
• Published: Dordrecht SP MAIK Nauka/Interperiodica 01-09-2010; Springer Nature B.V
• Subjects: Amino acids; Analgesics; Biochemistry; Bioorganic Chemistry; Chemistry; Chemistry and Materials Science; Experimental Studies; Liver; Medicinal Chemistry; Mitochondria; Oxidative stress; Rodents; Toxicity; tissue respiration; acetaminophen; melatonin; hepatotoxicity; hepatoprotectors; oxidative stress
• ISSN: 1990-7508; 1990-7516
• DOI: 10.1134/S199075081003008X

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 cell cytoplasm and mitochondria (at the dose 1500 mg/kg body weight by 60% and 33%, respectively). The decrease in cytoplasmic GSH level was more pronounced than in mitochondria. Despite of significant mitochondrial GSH depletion we did not observe any inactivation of the mitochondrial enzymes: succinate dehydrogenase, α-ketoglutarate dehydrogenase, glutathione peroxidase, and also any decrease in the respiratory activity of liver mitochondria isolated from APAP-intoxicated rats. We have investigated hepatoprotector properties of tryptophan derivatives, melatonin and N-acetyl-nitrosotryptophan (a nitric oxide donor). The pineal gland hormone, melatonin, a known antioxidant (10 mg/kg body weight), did not prevent intramitochondrial GSH, but decreased the APAP hepatotoxicity evaluated as the decrease in the activity of marker enzymes of hepatic damage, ALT and AST and total bilirubin content in blood plasma of intoxicated rats, whereas NNT did not exhibit any hepatoprotective effects.