S-adenosyl-l-methionine protection of acetaminophen mediated oxidative stress and identification of hepatic 4-hydroxynonenal protein adducts by mass spectrometry

Acetaminophen (APAP) hepatotoxicity is protected by S-adenosyl-l-methionine (SAMe) treatment 1hour (h) after APAP in C57/Bl6 mice. This study examined protein carbonylation as well as mitochondrial and cytosolic protein adduction by 4-hydroxynonenal (4-HNE) using mass spectrometry (MS) analysis. Add...

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Veröffentlicht in:	Toxicology and applied pharmacology 2014-12, Vol.281 (2), p.174-184
Hauptverfasser:	Brown, James Mike, Kuhlman, Christopher, Terneus, Marcus V., Labenski, Matthew T., Lamyaithong, Andre Benja, Ball, John G., Lau, Serrine S., Valentovic, Monica A.
Format:	Artikel
Sprache:	eng
Schlagworte:	4-Hydroxynonenal 60 APPLIED LIFE SCIENCES Acetaminophen ADDUCTS Aldehydes - metabolism Animals Antioxidants - pharmacology Biological and medical sciences Carbamoyl-Phosphate Synthase (Ammonia) - metabolism CARBONYLATION Chemical and Drug Induced Liver Injury - etiology Chemical and Drug Induced Liver Injury - metabolism Chemical and Drug Induced Liver Injury - prevention & control Chromatography, Liquid Cytoprotection Disease Models, Animal Hepatotoxicity LEAKS LIGASES LIVER Liver - drug effects Liver - metabolism Male Mass spectrometry MASS SPECTROSCOPY Medical sciences METHIONINE MICE Mice, Inbred BALB C MITOCHONDRIA Mitochondria, Liver - drug effects Mitochondria, Liver - metabolism Oxidative stress Oxidative Stress - drug effects PHOSPHATES Protein adduction Protein Carbonylation Protein Processing, Post-Translational S-Adenosylmethionine - pharmacology SARCOSINE Sarcosine Dehydrogenase - metabolism Tandem Mass Spectrometry TOXICITY Toxicology WEIGHT
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Zusammenfassung:	Acetaminophen (APAP) hepatotoxicity is protected by S-adenosyl-l-methionine (SAMe) treatment 1hour (h) after APAP in C57/Bl6 mice. This study examined protein carbonylation as well as mitochondrial and cytosolic protein adduction by 4-hydroxynonenal (4-HNE) using mass spectrometry (MS) analysis. Additional studies investigated the leakage of mitochondrial proteins and 4-HNE adduction of these proteins. Male C57/Bl6 mice (n=5/group) were divided into the following groups and treated as indicated: Veh (15ml/kg water, ip), SAMe (1.25mmol/kg, ip), APAP (250mg/kg), and SAMe given 1h after APAP (S+A). APAP toxicity was confirmed by an increase (p
ISSN:	0041-008X 1096-0333
DOI:	10.1016/j.taap.2014.08.027