1. HIF1a Inhibitor Rescues Acute-on-Chronic Liver Failure
- Author
-
Dexi Chen, Qinghua Meng, Jinling Dong, Fang Xie, Kefei Wang, Xuemei Liu, and Yueke Zhu
- 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 - 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.
- Published
- 2019