Small Molecule Chemistry | Drug Discovery & Design | Toxicology | Liver Biology & Pathobiology
Novel protective mechanisms for acetaminophen (APAP) hepatic toxicity by S-adenosyl-L-methionine (SAMe)
J Mike Brown, Andre Benja Lamyaithong, Stephanie Van Meter, John G Ball, Amber Mills, Michael Wright, Monica Valentovic*
*Corresponding author: Monica Valentovic
Department of Pharmacology, Marshall University School of Medicine, Huntington, WV, USA
F1000Posters 2012, 3: 263 (poster) [English]
Society of Toxicology Annual Meeting & ToxExpo 2012, 11 - 15 Mar 2012, 514
Acetaminophen (APAP) overdose induces severe hepatotoxicity. S-adenosyl-L-methionine (SAMe) reduces APAP toxicity when administered one hour after APAP. This study explored APAP induced leakage of mitochondrial enzymes and the extent of 4-HNE adduction of these proteins. This study also examined changes in the polyamine pathway induced by SAMe and APAP.
- SAMe markedly reduced APAP toxicity, as indicated by the moderation of alanine transaminase (ALT).
- APAP resulted in higher mitochondrial protein adduction by 3-nitrotyrosine (3-NT), a result that was lowered by SAMe.
- APAP induced an increase in mitochondrial leakage of carbamoyl phosphate synthase (CPS-1) into the cytosol, the extent of which was reduced by SAMe.
- SAMe helped to maintain the polyamine pathway in APAP overdose, and decreased 4-HNE adduction of CPS-1.
Further studies are needed to examine the extent of adduction of other mitochondrial proteins by APAP, and subsequent modulation by SAMe. Further studies will evaluate the mechanism for SAMe attenuation of APAP toxicity.
No relevant competing interests disclosed.
National Institutes of Health (NIH), 3P20RR016477-09S4
National Institutes of Health (NIH), 5P20RR016477
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