Acetaminophen inhibits hemoprotein-catalyzed lipid peroxidation and attenuates rhabdomyolysis-induced renal failure.

Boutaud O, Moore KP, Reeder BJ, Harry D, Howie AJ, Wang S, Carney CK, Masterson TS, Amin T, Wright DW, Wilson MT, Oates JA, Roberts LJ
Proc Natl Acad Sci U S A. 2010 107 (6): 2699-704

PMID: 20133658 · PMCID: PMC2823910 · DOI:10.1073/pnas.0910174107

Hemoproteins, hemoglobin and myoglobin, once released from cells can cause severe oxidative damage as a consequence of heme redox cycling between ferric and ferryl states that generates radical species that induce lipid peroxidation. We demonstrate in vitro that acetaminophen inhibits hemoprotein-induced lipid peroxidation by reducing ferryl heme to its ferric state and quenching globin radicals. Severe muscle injury (rhabdomyolysis) is accompanied by the release of myoglobin that becomes deposited in the kidney, causing renal injury. We previously showed in a rat model of rhabdomyolysis that redox cycling between ferric and ferryl myoglobin yields radical species that cause severe oxidative damage to the kidney. In this model, acetaminophen at therapeutic plasma concentrations significantly decreased oxidant injury in the kidney, improved renal function, and reduced renal damage. These findings also provide a hypothesis for potential therapeutic applications for acetaminophen in diseases involving hemoprotein-mediated oxidative injury.

MeSH Terms (20)

Acetaminophen Animals Arachidonic Acids Catalysis Dose-Response Relationship, Drug Hemeproteins Hemoglobins Humans Hydrogen-Ion Concentration Hydrogen Peroxide Iron Lipid Peroxidation Male Myoglobin Oxidation-Reduction Rats Rats, Sprague-Dawley Renal Insufficiency Rhabdomyolysis Spectrophotometry

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