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Effect of paracetamol on mitochondrial membrane function in rat liver slices

Effect of paracetamol on mitochondrial membrane function in rat liver slices
Effect of paracetamol on mitochondrial membrane function in rat liver slices

The effect of paracetamol on mitochondrial function was studied using rat liver slices. Changes in the potential of the mitochondrial and plasma membrane were monitored using [3H]-triphenylmethylphosphonium (TPMP+) and [14C]thiocyanate (SCN-) probes, respectively. Liver slices were exposed to 10 mM paracetamol for various time periods (0-360 min) after loading with TPMP+. The release of TPMP+ which correlates with a decrease in the mitochondrial membrane potential became significant after 30 min incubation with 10 mM paracetamol. The change in the mitochondrial membrane potential was shown to be independent of cytochrome P450 activity. No significant change in plasma membrane potential was observed, until the release of lactate dehydrogenase (LDH) had begun, 4 hr after exposure, reflecting the ultimate stages of cell injury by paracetamol. These results suggest that paracetamol elicits a direct effect on the mitochondrial function before cell injury develops and adds further evidence to the role of mitochondria in paracetamol toxicity.

Acetaminophen, Animals, Carbonyl Cyanide m-Chlorophenyl Hydrazone, Cell Membrane, Cysteine, Intracellular Fluid, Intracellular Membranes, Liver, Male, Membrane Potentials, Mitochondria, Liver, Onium Compounds, Pyridines, Rats, Rats, Inbred Strains, Thiocyanates, Trityl Compounds, Journal Article, Research Support, Non-U.S. Gov't
0006-2952
931-936
Nazareth, W.M.
a8d5cc8b-7db1-4f29-a2b2-f81e9b41f6c1
Sethi, J.K.
923f1a81-91e4-46cd-8853-bb4a979f5a85
McLean, A.E.M.
41ebe88e-ff9c-4ec8-8cc1-c9e51c6e3278
Nazareth, W.M.
a8d5cc8b-7db1-4f29-a2b2-f81e9b41f6c1
Sethi, J.K.
923f1a81-91e4-46cd-8853-bb4a979f5a85
McLean, A.E.M.
41ebe88e-ff9c-4ec8-8cc1-c9e51c6e3278

Nazareth, W.M., Sethi, J.K. and McLean, A.E.M. (1991) Effect of paracetamol on mitochondrial membrane function in rat liver slices. Biochemical Pharmacology, 42 (4), 931-936. (doi:10.1016/0006-2952(91)90055-A).

Record type: Article

Abstract

The effect of paracetamol on mitochondrial function was studied using rat liver slices. Changes in the potential of the mitochondrial and plasma membrane were monitored using [3H]-triphenylmethylphosphonium (TPMP+) and [14C]thiocyanate (SCN-) probes, respectively. Liver slices were exposed to 10 mM paracetamol for various time periods (0-360 min) after loading with TPMP+. The release of TPMP+ which correlates with a decrease in the mitochondrial membrane potential became significant after 30 min incubation with 10 mM paracetamol. The change in the mitochondrial membrane potential was shown to be independent of cytochrome P450 activity. No significant change in plasma membrane potential was observed, until the release of lactate dehydrogenase (LDH) had begun, 4 hr after exposure, reflecting the ultimate stages of cell injury by paracetamol. These results suggest that paracetamol elicits a direct effect on the mitochondrial function before cell injury develops and adds further evidence to the role of mitochondria in paracetamol toxicity.

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More information

Accepted/In Press date: 1 May 1991
Published date: 25 July 1991
Keywords: Acetaminophen, Animals, Carbonyl Cyanide m-Chlorophenyl Hydrazone, Cell Membrane, Cysteine, Intracellular Fluid, Intracellular Membranes, Liver, Male, Membrane Potentials, Mitochondria, Liver, Onium Compounds, Pyridines, Rats, Rats, Inbred Strains, Thiocyanates, Trityl Compounds, Journal Article, Research Support, Non-U.S. Gov't

Identifiers

Local EPrints ID: 421031
URI: http://eprints.soton.ac.uk/id/eprint/421031
ISSN: 0006-2952
PURE UUID: 1085fc0f-ce59-49ac-9ee4-d2eca369d506
ORCID for J.K. Sethi: ORCID iD orcid.org/0000-0003-4157-0475

Catalogue record

Date deposited: 21 May 2018 16:30
Last modified: 10 Nov 2021 03:48

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Contributors

Author: W.M. Nazareth
Author: J.K. Sethi ORCID iD
Author: A.E.M. McLean

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