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Impaired mitochondrial oxidative energy metabolism following paracetamol‐induced hepatotoxicity in the rat
Author(s) -
Katyare Surendra S.,
Satav Jagannath G.
Publication year - 1989
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1989.tb11783.x
Subject(s) - mitochondrion , oxidative phosphorylation , respiration , succinate dehydrogenase , bioenergetics , acetaminophen , pharmacology , chemistry , in vivo , atpase , metabolism , liver injury , biochemistry , medicine , endocrinology , biology , enzyme , anatomy , microbiology and biotechnology
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 + c 1 while the toxic doses caused lowering of the cytochromes aa 3 and b contents. 6 Glutamate and succinate dehydrogenase activities decreased in both the experimental groups while Mg 2+ ‐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.