Inhibition of lipolysis: A novel explanation for the hypothermic actions of acetaminophen in non-febrile rodents

Article


Bashir, S., Elegunde, B. and Morgan, W. 2020. Inhibition of lipolysis: A novel explanation for the hypothermic actions of acetaminophen in non-febrile rodents. Biochemical Pharmacology. 172 (Art. 113774). https://doi.org/10.1016/j.bcp.2019.113774
AuthorsBashir, S., Elegunde, B. and Morgan, W.
Abstract

Acetaminophen is both widely used to treat children with fever and is also responsible for thousands being hospitalised annually. Historically the antipyretic actions of acetaminophen were attributed to the inhibition of cyclooxygenase (COX-1/2) enzymes and more recently a novel COX-1 variant (COX-3) located in the brain. However, the evidence for acetaminophen-mediated COX inhibition remains contentious. This study assesses the impact of acetaminophen and other putative COX-3 inhibitors on the release of fatty acids during lipolysis as an alternative mechanism by which antipyretics can reduce body temperature during fever. 3T3-L1 adipocytes, primary brown adipocytes and isolated mitochondria were exposed to COX-3 inhibitors and lipolysis and mitochondrial electron transport chain function assessed. Acetaminophen, aminopyrine and antipyrine at 1–10 mM caused a significant decrease (up to 70%; P < 0.01, from control) in lipolysis within 1, 3 and 24 h without affecting cell viability. The inhibition was observed regardless of where along its signalling pathway lipolysis was stimulated. All three compounds were found to significantly attenuate mitochondrial function by up to 30% for complex I and 40% for complex II (P < 0.01, from control). These novel observations combined with the known limited inhibition of the COX enzymes by acetaminophen suggest both the antipyretic and hypothermia induced by acetaminophen and related compounds could be attributed to the direct inhibition of lipolysis and mitochondrial function, rather than cyclooxygenase inhibition centrally. Further these observations could provide new drug targets for reducing fever with the added bonus of fewer individuals being hospitalized by accidental acetaminophen overdose.

JournalBiochemical Pharmacology
Journal citation172 (Art. 113774)
ISSN0006-2952
Year2020
PublisherElsevier
Accepted author manuscript
License
File Access Level
Anyone
Digital Object Identifier (DOI)https://doi.org/10.1016/j.bcp.2019.113774
Web address (URL)https://doi.org/10.1016/j.bcp.2019.113774
Publication dates
Online21 Dec 2019
Publication process dates
Accepted18 Dec 2019
Deposited08 Jan 2020
Copyright holder© 2020 Elsevier
Permalink -

https://repository.uel.ac.uk/item/87705

Download files


Accepted author manuscript
BCP-S-19-02890.pdf
License: CC BY-NC-ND 4.0
File access level: Anyone

  • 214
    total views
  • 113
    total downloads
  • 0
    views this month
  • 0
    downloads this month

Export as

Related outputs

Cough syrup can harm children: experts warn of contamination risks
Morgan, W. and Bashir, S. 2023. Cough syrup can harm children: experts warn of contamination risks. The Conversation.
Comparative Analysis of Tick-Borne Relapsing Fever Spirochaetes from Ethiopia and Nigeria
Bankole, A. A., Kumsa, B., Mamo, G., Ogo, N. I., Elelu, N., Morgan, W. and Cutler, S. J. 2023. Comparative Analysis of Tick-Borne Relapsing Fever Spirochaetes from Ethiopia and Nigeria. Pathogens. 12 (Art. 81). https://doi.org/10.3390/pathogens12010081
Tackling inequalities in research
Morgan, W. 2022. Tackling inequalities in research. The Biologist.
Inhibition of mitochondrial function: An alternative explanation for the antipyretic and hypothermic actions of acetaminophen
Bashir, S. and Morgan, W. 2022. Inhibition of mitochondrial function: An alternative explanation for the antipyretic and hypothermic actions of acetaminophen. Life Sciences. 312 (Art. 121194). https://doi.org/10.1016/j.lfs.2022.121194
Coronavirus: heavy use of hand sanitisers could boost antimicrobial resistance
Morgan, W. 2020. Coronavirus: heavy use of hand sanitisers could boost antimicrobial resistance . The Conversation.
Prebiotics may alter bile salt hydrolase activity: Possible implications for cholesterol metabolism
Adebola, O., Corcoran, O. and Morgan, W. 2020. Prebiotics may alter bile salt hydrolase activity: Possible implications for cholesterol metabolism. PharmaNutrition. 12 (Art. 100182). https://doi.org/10.1016/j.phanu.2020.100182
No black scientist has ever won a Nobel – that’s bad for science, and bad for society
Morgan, W. 2018. No black scientist has ever won a Nobel – that’s bad for science, and bad for society. The Conversation.
Mechanism of Paracetamol (Acetaminophen) induced Hypothermia
Bashir, S. 2018. Mechanism of Paracetamol (Acetaminophen) induced Hypothermia. PhD Thesis University of East London Health, Sport & Bioscience https://doi.org/10.15123/PUB.7308
The requirement of p38-MAPKinase and peroxisome proliferator-activated receptor-g for the induction of cyclooxygenase-2 by interleukin-4 drives macrophages into an anti-inflammatory phenotype
Manoj, Sivanjaa, Morgan, W. and Ayoub, S. 2017. The requirement of p38-MAPKinase and peroxisome proliferator-activated receptor-g for the induction of cyclooxygenase-2 by interleukin-4 drives macrophages into an anti-inflammatory phenotype. Pharmacology 2017. Queen Elizabeth II Conference Centre, London, UK 11 - 13 Dec 2017
Transformation of monocytes to macrophages by combination antiretroviral treatment
Mafuva, Christopher and Morgan, W. 2016. Transformation of monocytes to macrophages by combination antiretroviral treatment. PHARMACOLOGY 2016. The Queen Elizabeth II Conference Centre, London 13 - 15 Dec 2016
Antipyresis and the inhibition of mitochondrial function
Elegunde, Busayo, Bashir, Shazma and Morgan, W. 2016. Antipyresis and the inhibition of mitochondrial function. PHARMACOLOGY 2016. The Queen Elizabeth II Conference Centre, London 13 - 15 Dec 2016
Effect of contraceptive hormones on a nevirapine based antiretroviral combination treatment induced apoptosis in human cervical epithelial cancer cells
Mafuva, Christopher and Morgan, W. 2017. Effect of contraceptive hormones on a nevirapine based antiretroviral combination treatment induced apoptosis in human cervical epithelial cancer cells. 32nd Annual Conference on Genes & Cancer. Robinson College, University of Cambridge, Cambridge, United Kingdom 10 - 12 Apr 2017
Characterisation of the signalling mechanisms involved in the induction of cyclooxygenase-2 by interleukin-4
Sivanjaa Manoj, Manoj, Morgan, W. and Ayoub, S. 2016. Characterisation of the signalling mechanisms involved in the induction of cyclooxygenase-2 by interleukin-4. PHARMACOLOGY 2016. The Queen Elizabeth II Conference Centre, London 13 - 15 Dec 2016 London British Pharmacological Society.
Evaluation of Antibacterial Activity and Phytoconstituents of the Aqueous Leaves Extract of Alchornea Cordifolia
Antepim Pesewu, George, Culter, Ronald R., Humber, David P. and Morgan, W. 2015. Evaluation of Antibacterial Activity and Phytoconstituents of the Aqueous Leaves Extract of Alchornea Cordifolia. International Scientific Research Journal. 1 (07), pp. 48-54. https://doi.org/10.18483/IRJSci.54
Protective effects of prebiotics inulin and lactulose from cytotoxicity and genotoxicity in human colon adenocarcinoma cells
Adebola, O., Corcoran, O. and Morgan, W. 2013. Protective effects of prebiotics inulin and lactulose from cytotoxicity and genotoxicity in human colon adenocarcinoma cells. Food Research International. 52 (1), pp. 269-274. https://doi.org/10.1016/j.foodres.2013.03.024
The ethanol extract of Scutellaria baicalensis and the active compounds induce cell cycle arrest and apoptosis including upregulation of p53 and Bax in human lung cancer cells
Gao, J., Morgan, W., Sanchez-Medina, A. and Corcoran, O. 2011. The ethanol extract of Scutellaria baicalensis and the active compounds induce cell cycle arrest and apoptosis including upregulation of p53 and Bax in human lung cancer cells. Toxicology and Applied Pharmacology. 254 (3), pp. 221-228. https://doi.org/10.1016/j.taap.2011.03.016
Ethnopharmacological survey and in vitro evaluation of wound-healing plants used in South-western Nigeria
Adetutu, A., Morgan, W. and Corcoran, O. 2011. Ethnopharmacological survey and in vitro evaluation of wound-healing plants used in South-western Nigeria. Journal of Ethnopharmacology. 137, pp. 50-56. https://doi.org/10.1016/j.jep.2011.03.073
Antibacterial, antioxidant and fibroblast growth stimulation activity of crude extracts of Bridelia ferruginea leaf, a wound-healing plant of Nigeria
Adetutu, A., Morgan, W. and Corcoran, O. 2010. Antibacterial, antioxidant and fibroblast growth stimulation activity of crude extracts of Bridelia ferruginea leaf, a wound-healing plant of Nigeria. Journal of Ethnopharmacology. 133 (1), pp. 116-119. https://doi.org/10.1016/j.jep.2010.09.011