Abstract
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.
Highlights
Metabolism of mammals is subjected to permanent modulations, with the essential role played by the change in enzymatic activity due to different factors, e.g. drugs
Our results suggested that long term exposure to PC (8 and 12 weeks) decreased activity of glutathione peroxidase (GPX) enzyme and increased activity of GST and glutathione reductase (GR) enzymes as well as increased level of lipid peroxidation process in rat liver
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
Summary
Metabolism of mammals is subjected to permanent modulations, with the essential role played by the change in enzymatic activity due to different factors, e.g. drugs. A part of the ingested drug dose is coupled in liver with glucuronic acid (60%), active sulfonic acid or glycine, and excreted with urine in the form of such compounds [6,7,8]. The remaining part of paracetamol is metabolised by cytochrome P-450 in liver to a non-toxic catechol and toxically acting N-acetylp-bensoquinone-imine (NAPQI), which injures hepatocytes. Accumulation of this metabolite can lead to liver necrosis [4,9]. 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
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