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NRF2 Protection against Liver Injury Produced by Various Hepatotoxicants
Joint Authors
Ekuase, Edugie
Wu, Kai Connie
Lu, Yuan-Fu
Klaassen, Curtis D.
Liu, Jie
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2013, Issue 2013 (31 Dec. 2013), pp.1-8, 8 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2013-05-23
Country of Publication
Egypt
No. of Pages
8
Main Subjects
Natural & Life Sciences (Multidisciplinary)
Biology
Abstract EN
To investigate the role of Nrf2 as a master defense against the hepatotoxicity produced by various chemicals, Nrf2-null, wild-type, Keap1-knock down (Keap1-Kd) and Keap1-hepatocyte knockout (Keap1-HKO) mice were used as a “graded Nrf2 activation” model.
Mice were treated with 14 hepatotoxicants at appropriate doses, and blood and liver samples were collected thereafter (6 h to 7 days depending on the hepatotoxicant).
Graded activation of Nrf2 offered a Nrf2-dependent protection against the hepatotoxicity produced by carbon tetrachloride, acetaminophen, microcystin, phalloidin, furosemide, cadmium, and lithocholic acid, as evidenced by serum alanine aminotransferase (ALT) activities and by histopathology.
Nrf2 activation also offered moderate protection against liver injury produced by ethanol, arsenic, bromobenzene, and allyl alcohol but had no effects on the hepatotoxicity produced by D-galactosamine/endotoxin and the Fas ligand antibody Jo-2.
Graded Nrf2 activation reduced the expression of inflammatory genes (MIP-2, mKC, IL-1β, IL-6, and TNFα), oxidative stress genes (Ho-1, Egr1), ER stress genes (Gadd45 and Gadd153), and genes encoding cell death (Noxa, Bax, Bad, and caspase3).
Thus, this study demonstrates that Nrf2 prevents the liver from many, but not all, hepatotoxicants.
The Nrf2-mediated protection is accompanied by induction of antioxidant genes, suppression of inflammatory responses, and attenuation of oxidative stress.
American Psychological Association (APA)
Liu, Jie& Wu, Kai Connie& Lu, Yuan-Fu& Ekuase, Edugie& Klaassen, Curtis D.. 2013. NRF2 Protection against Liver Injury Produced by Various Hepatotoxicants. Oxidative Medicine and Cellular Longevity،Vol. 2013, no. 2013, pp.1-8.
https://search.emarefa.net/detail/BIM-461992
Modern Language Association (MLA)
Liu, Jie…[et al.]. NRF2 Protection against Liver Injury Produced by Various Hepatotoxicants. Oxidative Medicine and Cellular Longevity No. 2013 (2013), pp.1-8.
https://search.emarefa.net/detail/BIM-461992
American Medical Association (AMA)
Liu, Jie& Wu, Kai Connie& Lu, Yuan-Fu& Ekuase, Edugie& Klaassen, Curtis D.. NRF2 Protection against Liver Injury Produced by Various Hepatotoxicants. Oxidative Medicine and Cellular Longevity. 2013. Vol. 2013, no. 2013, pp.1-8.
https://search.emarefa.net/detail/BIM-461992
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-461992