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HIF1a Inhibitor Rescues Acute-on-Chronic Liver Failure
- Source :
- Annals of Hepatology, Vol 18, Iss 5, Pp 757-764 (2019)
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- Introduction and Objectives Hypoxia-inducible factor-1α is critically involved in the pathogenesis of liver diseases. Its inhibitor genistein attenuated D-galactosamine (D-GalN)-induced liver damage. However, the role of genistein in acute-on-chronic liver failure (ACLF) is unclear. The influence of genistein on reactive oxygen species (ROS) and hepatocyte functions were evaluated in a rat model of ACLF. Material and methods Genistein [20 mg/ (kg. day)]/coenzyme Q10 [10 mg/ (kg. day)]/lipoic acid [20 mg/ (kg. day)] was administered via the intra-gastric route daily for 6 weeks as co-treatment to the rats in the experimental groups. Then, 100 μg/kg LPS combined with 0.5 g/kg D-GalN was injected intraperitoneally to attack the rats. Results Genistein significantly attenuated LPS/D-GalN-induced ACLF, characterized by ameliorated gross appearance and microscopic histopathology of liver, reduced AST level in serum, whereas increased levels of ATP, ADP/O, and respiratory control ratio (RCR) in mitochondria. Genistein suppressed necrosis and ROS production. Conclusion These results suggested that genistein could protect against ACLF through inhibiting cellular ROS production and necrosis, improving RCR, and decreasing permeability transition pores in mitochondrial, which was similar as mitochondrial protective agent coenzyme Q10.
- Subjects :
- Male
Necrosis
Specialties of internal medicine
Genistein
Mitochondrion
Pharmacology
Rats, Sprague-Dawley
Pathogenesis
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
medicine
Animals
Protein Kinase Inhibitors
chemistry.chemical_classification
Coenzyme Q10
Reactive oxygen species
Hepatology
business.industry
Hypoxia-inducible factor-1α
Acute-On-Chronic Liver Failure
General Medicine
Hypoxia-Inducible Factor 1, alpha Subunit
Rats
Disease Models, Animal
Lipoic acid
medicine.anatomical_structure
RC581-951
Liver
chemistry
030220 oncology & carcinogenesis
Hepatocyte
030211 gastroenterology & hepatology
medicine.symptom
Reactive Oxygen Species
business
Biomarkers
Subjects
Details
- ISSN :
- 16652681
- Volume :
- 18
- Database :
- OpenAIRE
- Journal :
- Annals of Hepatology
- Accession number :
- edsair.doi.dedup.....4cf299ed174372c289e7f08db55e78bc