期刊
BIOMED RESEARCH INTERNATIONAL
卷 2013, 期 -, 页码 -出版社
HINDAWI LTD
DOI: 10.1155/2013/627046
关键词
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资金
- SETI/Fundacao Araucaria
- Parana State Government
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
- Coordenadoria de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), Brazil
- Departamento de Ciencia e Tecnologia da Secretaria de Ciencia, Tecnologia e Insumos Estrategicos (Decit/SCTIE)
- Ministerio da Saude (MS) (Decit/SCTIE/MS) of CNPq
- Fundacao Araucaria
5-Lipoxygenase (5-LO) converts arachidonic acid into leukotrienes (LTs) and is involved in inflammation. At present, the participation of 5-LO in acetaminophen (APAP)-induced hepatotoxicity and liver damage has not been addressed. 5-LO deficient (5-LO-/-) mice and background wild type mice were challenged with APAP (0.3-6 g/kg) or saline. The lethality, liver damage, neutrophil and macrophage recruitment, LTB4, cytokine production, and oxidative stress were assessed. APAP induced a dose-dependent mortality, and the dose of 3 g/kg was selected for next experiments. APAP induced LTB4 production in the liver, the primary target organ in APAP toxicity. Histopathological analysis revealed that 5-LO-/- mice presented reduced APAP-induced liver necrosis and inflammation compared with WT mice. APAP-induced lethality, increase of plasma levels of aspartate aminotransferase and alanine aminotransferase, liver cytokine (IL-1 beta, TNF-alpha, IFN-gamma, and IL-10), superoxide anion, and thiobarbituric acid reactive substances production, myeloperoxidase and N-acetyl-beta-D-glucosaminidase activity, Nrf2 and gp91(phox) mRNA expression, and decrease of reduced glutathione and antioxidant capacity measured by 2,2'-azinobis(3-ethylbenzothiazoline 6-sulfonate) assay were prevented in 5-LO-/- mice compared to WT mice. Therefore, 5-LO deficiency resulted in reduced mortality due to reduced liver inflammatory and oxidative damage, suggesting 5-LO is a promising target to reduce APAP-induced lethality and liver inflammatory/oxidative damage.
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