Acylcarnitine Profiles in Acetaminophen Toxicity in the Mouse: Comparison to Toxicity, Metabolism and Hepatocyte Regeneration
| العنوان: | Acylcarnitine Profiles in Acetaminophen Toxicity in the Mouse: Comparison to Toxicity, Metabolism and Hepatocyte Regeneration |
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| المؤلفون: | Sudeepa Bhattacharyya, Lisa Pence, Sandra S. McCullough, Shubhra Chaudhuri, Leah Hennings, Richard D. Beger, Pippa Simpson, Jack A. Hinson, Ke Yan, Laura P. James |
| المصدر: | Metabolites Metabolites, Vol 3, Iss 3, Pp 606-622 (2013) Metabolites; Volume 3; Issue 3; Pages: 606-622 |
| بيانات النشر: | MDPI, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | NAPQI, Endocrinology, Diabetes and Metabolism, lcsh:QR1-502, Biology, Pharmacology, 030226 pharmacology & pharmacy, Biochemistry, lcsh:Microbiology, Article, acylcarnitine, 03 medical and health sciences, 0302 clinical medicine, medicine, Carnitine, Molecular Biology, 030304 developmental biology, acetaminophen, chemistry.chemical_classification, 0303 health sciences, digestive, oral, and skin physiology, Fatty acid, toxicity, Metabolism, Liver regeneration, 3. Good health, Acetaminophen, medicine.anatomical_structure, chemistry, Hepatocyte, Toxicity, β-oxidation, hepatic, medicine.drug |
| الوصف: | High doses of acetaminophen (APAP) result in hepatotoxicity that involves metabolic activation of the parent compound, covalent binding of the reactive intermediate N-acetyl-p-benzoquinone imine (NAPQI) to liver proteins, and depletion of hepatic glutathione. Impaired fatty acid β-oxidation has been implicated in previous studies of APAP-induced hepatotoxicity. To better understand relationships between toxicity and fatty acid β-oxidation in the liver in APAP toxicity, metabolomic assays for long chain acylcarnitines were examined in relationship to established markers of liver toxicity, oxidative metabolism, and liver regeneration in a time course study in mice. Male B6C3F1 mice were treated with APAP (200 mg/kg IP) or saline and sacrificed at 1, 2, 4, 8, 24 or 48 h after APAP. At 1 h, hepatic glutathione was depleted and APAP protein adducts were markedly increased. Alanine aminotransferase (ALT) levels were elevated at 4 and 8 h, while proliferating cell nuclear antigen (PCNA) expression, indicative of hepatocyte regeneration, was apparent at 24 h and 48 h. Elevations of palmitoyl, oleoyl and myristoyl carnitine were apparent by 2–4 h, concurrent with the onset of Oil Red O staining in liver sections. By 8 h, acylcarnitine levels were below baseline levels and remained low at 24 and 48 h. A partial least squares (PLS) model suggested a direct association of acylcarnitine accumulation in serum to APAP protein adduct and hepatic glutathione levels in mice. Overall, the kinetics of serum acylcarnitines in APAP toxicity in mice followed a biphasic pattern involving early elevation after the metabolism phases of toxicity and later depletion of acylcarnitines. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2218-1989 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::59a60d45ba5df08effa04108266b6ef1 http://europepmc.org/articles/PMC3901280 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....59a60d45ba5df08effa04108266b6ef1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22181989 |
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