生物等效性和生物利用度杂志

抽象的

Long-term Exposure to Acetaminophen is a Crucial for Activity of Selected Antioxidative Enzymes and Level of Lipid Peroxidation Process in Rat Liver

Renata Polaniak, Rafal Jakub Buldak, Wojciech Jachec, Krzysztof Helewski, Romuald Wojnicz, Ewa Birkner, Michal Kukla, Marcin Gowarzewski, Robert Kubina and Krystyna Zwirska-Korczala

Background: Our aim was to investigate the effect of intra-oesophageal acetaminophen instillation on the selected antioxidative enzymes activity: superoxide dismutase isoenzymes (MnSOD, Cu/ZnSOD), glutathione peroxidase (GPX), glutathione-S-transferase (GST), glutathione reductase (GR) and lipid peroxidation in rat liver after 4, 8 and 12 weeks of exposure. Material and methods: Male Wistar FL strain rats weighing 150-160 g were treated with paracetamol by intra- oesophageal instillation at a dose of 2.4 g/kg b.w every day up to 12 weeks. During the whole experiment rats were kept in a night-and-day’s cycle lasting twelve hours, with standard feed ad libitum . Rats were sacrificed after 4, 8 and 12 weeks of the study. The collected tissue liver was homogenized and the above mentioned enzymes were determined in the supernatants. Results: The current study revealed the presence of paracetamol-induced changes in the activities of antioxidative enzymes in comparison to the control values. Our results suggested that long term exposure to PC (8 and 12 weeks) decreased activity of GPX enzyme and increased activity of GST and GR enzymes as well as increased level of lipid peroxidation process in rat liver. These changes in the activity of antioxidative enzymes may be involved in paracetamol toxicity of the liver after a longer time of exposure to PC. The cited literature and our findings show that excessive use of paracetamol-containing preparations can have a harmful effect upon liver metabolism and suggest the need for further research.