Impaired mitochondrial oxidative energy metabolism following paracetamol‐induced hepatotoxicity in the rat

• Published in: British journal of pharmacology 1989-01, Vol.96 (1), p.51-58
• Main Authors: Katyare, Surendra S., Satav, Jagannath G.
• Format: Article
• Language: English
• Subjects: Acetaminophen - toxicity; Adenosine Triphosphatases - metabolism; Animals; Biological and medical sciences; Body Weight - drug effects; Cytochromes - analysis; Drug toxicity and drugs side effects treatment; Energy Metabolism - drug effects; Liver - drug effects; Male; Medical sciences; Mitochondria, Liver - drug effects; Mitochondria, Liver - enzymology; Organ Size - drug effects; Oxidative Phosphorylation - drug effects; Oxidoreductases - metabolism; Pharmacology. Drug treatments; Rats; Rats, Inbred Strains; Toxicity: digestive system
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1989.tb11783.x

1 Effects of paracetamol treatment in vivo at subtoxic (375 mg kg−1 body weight) and toxic (750 mg kg−1 body weight) doses on energy metabolism in rat liver mitochondria were examined. 2 Paracetamol treatment resulted in a significant loss in body weights without affecting the liver protein contents. Toxic doses, however, resulted in 21% decrease in the yield of mitochondrial proteins. 3 Subtoxic doses of paracetamol did not, in general, affect the respiratory parameters in the liver mitochondria except in the case of succinate where both the state 3 respiration and the ADP‐phosphorylation rates increased by 28%. 4 Toxic doses of paracetamol caused 25 to 47% decrease in the state 3 respiration rates depending on the substrate used. ADP/O ratios also decreased significantly with pyruvate + malate and succinate as the substrates. Consequently, ADP‐phosphorylation was impaired significantly from 20 to 63%. 5 Subtoxic doses of paracetamol resulted in increased contents of cytochrome c + c1 while the toxic doses caused lowering of the cytochromes aa3 and b contents. 6 Glutamate and succinate dehydrogenase activities decreased in both the experimental groups while Mg2+‐ATPase activity was impaired only after toxic dose‐treatment. 7 The results show that toxic doses of paracetamol result in impaired energy coupling in the liver mitochondria. Effects of subtoxic doses were also demonstrable in terms of impaired dehydrogenases activities.