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5-Lipoxygenase Deficiency Reduces Acetaminophen-Induced Hepatotoxicity and Lethality
Joint Authors
Cunha, Fernando Queiroz
Cunha, Thiago Mattar
Casagrande, Rúbia
Verri, Waldiceu A.
Cardoso, Renato D. R.
Pinho-Ribeiro, Felipe A.
Crespigio, Jefferson
Hohmann, Miriam S. N.
Ferreira, Sergio Henrique
Alves-Filho, José C.
da Silva, Rosiane V.
Pinge-Filho, Phileno
Source
Issue
Vol. 2013, Issue 2013 (31 Dec. 2013), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2013-10-31
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
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-1β, TNF-α, IFN-γ, and IL-10), superoxide anion, and thiobarbituric acid reactive substances production, myeloperoxidase and N-acetyl-β-D-glucosaminidase activity, Nrf2 and gp91phox 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.
American Psychological Association (APA)
Hohmann, Miriam S. N.& Cardoso, Renato D. R.& Pinho-Ribeiro, Felipe A.& Crespigio, Jefferson& Cunha, Thiago Mattar& Alves-Filho, José C.…[et al.]. 2013. 5-Lipoxygenase Deficiency Reduces Acetaminophen-Induced Hepatotoxicity and Lethality. BioMed Research International،Vol. 2013, no. 2013, pp.1-13.
https://search.emarefa.net/detail/BIM-1030734
Modern Language Association (MLA)
Hohmann, Miriam S. N.…[et al.]. 5-Lipoxygenase Deficiency Reduces Acetaminophen-Induced Hepatotoxicity and Lethality. BioMed Research International No. 2013 (2013), pp.1-13.
https://search.emarefa.net/detail/BIM-1030734
American Medical Association (AMA)
Hohmann, Miriam S. N.& Cardoso, Renato D. R.& Pinho-Ribeiro, Felipe A.& Crespigio, Jefferson& Cunha, Thiago Mattar& Alves-Filho, José C.…[et al.]. 5-Lipoxygenase Deficiency Reduces Acetaminophen-Induced Hepatotoxicity and Lethality. BioMed Research International. 2013. Vol. 2013, no. 2013, pp.1-13.
https://search.emarefa.net/detail/BIM-1030734
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1030734