Nonsteroidal antiinflammatory drugs and uncoupling of mitochondrial oxidative phosphorylation

Arthritis and Rheumatism
T MahmudI Bjarnason

Abstract

There is a lack of correlation between cyclooxygenase (COX) inhibition and nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal (GI) damage; it has been suggested that mucosal damage may be initiated by a "topical" action of NSAIDs involving mitochondrial injury. We evaluated the effect of a range of NSAIDs and related compounds on mitochondrial function and assessed the differences between them in relation to their physicochemical properties. Stimulation of respiration, as an indicator of mitochondrial uncoupling, was measured in isolated coupled rat liver mitochondrial preparations, using an oxygen electrode. Conventional NSAIDs and acidic prodrugs all had stimulatory effects on mitochondrial respiration at micromolar concentrations (0.02-2.7 microM); higher concentrations were inhibitory. The uncoupling potency was inversely correlated with drug pKa (r = -0.87, P < 0.001; n = 12). Drugs known to have good GI tolerability, including modified flurbiprofen (dimero-flurbiprofen and nitrobutyl-flurbiprofen), nabumetone (a non-acidic prodrug), and non-acidic highly selective COX-2 inhibitors, did not cause uncoupling. The ability to uncouple mitochondrial oxidative phosphorylation is a common characteristic of anti...Continue Reading

References

Mar 28, 1987·Lancet·P E ClaytonD A Price
Jun 1, 1987·Archives of Internal Medicine·J L CarsonJ K Jones
Oct 1, 1980·British Journal of Clinical Pharmacology·K BruneA Schweitzer
Nov 1, 1980·Agents and Actions·K D Rainsford, M W Whitehouse
Apr 1, 1996·Annals of the Rheumatic Diseases·T MahmudI Bjarnason
Sep 24, 1971·Nature

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Citations

Dec 22, 2005·Der Pathologe·M Vieth
Jan 17, 2004·Chemico-biological Interactions·Clairce Luzia Salgueiro-PagadigorriaEmy L Ishii-Iwamoto
Aug 13, 2003·Gut·I BjarnasonR Simpson
Jun 3, 2000·Annual Review of Pharmacology and Toxicology·K B Wallace, A A Starkov
Jul 19, 2011·Journal of Clinical Biochemistry and Nutrition·Kanho RaiHideyuki J Majima
Feb 20, 2009·Journal of Gastroenterology·Ingvar Bjarnason, Ken Takeuchi
Oct 23, 2010·The International Journal of Neuroscience·Ibrahim Sogut, Gungor Kanbak
Nov 15, 2000·Critical Reviews in Clinical Laboratory Sciences·E Fosslien
Dec 23, 2015·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Muzeeb SyedSteen Honoré Hansen
Nov 28, 2015·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Muzeeb SyedSteen Honoré Hansen
Sep 29, 2011·Disease-a-month : DM·Muhammed Sherid, Eli D Ehrenpreis
Sep 22, 2010·The International Journal of Biochemistry & Cell Biology·Kristopher SilverJames D Lillich
Mar 17, 2010·Best Practice & Research. Clinical Gastroenterology·Zeino ZeinoIngvar Bjarnason
Jun 28, 2015·Cancer Letters·Ganji Purnachandra NagarajuBassel F El-Rayes
Aug 16, 2003·British Journal of Clinical Pharmacology·Simon Smale, Ingvar Bjarnason
Jun 9, 2007·Alimentary Pharmacology & Therapeutics·I BjarnasonK D Rainsford
Oct 17, 2006·Basic & Clinical Pharmacology & Toxicology·Samara LeiteAntonio Cardozo dos Santos
Mar 17, 2012·The Journal of Pharmacy and Pharmacology·Kim D Rainsford, Ingvar Bjarnason
Mar 1, 2005·Chemico-biological Interactions·Arno G SirakiPeter J O'Brien
Oct 7, 2004·European Journal of Pharmacology·Brendan J R Whittle
Jul 25, 2006·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·Zaher A Radi, Nasir K Khan
Sep 1, 1999·Rheumatic Diseases Clinics of North America·D VassilopoulosR M Strauss

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