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Histone deacetylase inhibitor givinostat attenuates nonalcoholic steatohepatitis and liver fibrosis

   
@article{APS10533,
	author = {He-ming Huang and Shi-jie Fan and Xiao-ru Zhou and Yan-jun Liu and Xiao Li and Li-ping Liao and Jing Huang and Cui-cui Shi and Liang Yu and Rong Fu and Jian-gao Fan and Yuan-yuan Zhang and Cheng Luo and Guang-ming Li},
	title = {Histone deacetylase inhibitor givinostat attenuates nonalcoholic steatohepatitis and liver fibrosis},
	journal = {Acta Pharmacologica Sinica},
	volume = {43},
	number = {4},
	year = {2022},
	keywords = {},
	abstract = {Nonalcoholic steatohepatitis (NASH) is a common chronic liver disease that is increasingly prevalent worldwide. Liver inflammation is an important contributor to disease progression from nonalcoholic fatty liver (NAFL) to NASH, but there is a lack of efficient therapies. In the current study we evaluated the therapeutic potential of givinostat, a histone deacetylase (HDAC) inhibitor, in the treatment of NASH in vivo and in vitro. Liver inflammation was induced in mice by feeding a methionine- and choline-deficient diet (MCD) or a fructose, palmitate, cholesterol diet (FPC). The mice were treated with givoinostat (10 mg·kg−1·d−1, ip) for 8 or 10 weeks. At the end of the experiment, the livers were harvested for analysis. We showed that givoinostat administration significantly alleviated inflammation and attenuated hepatic fibrosis in MCD-induced NASH mice. RNA-seq analysis of liver tissues form MCD-fed mice revealed that givinostat potently blocked expression of inflammation-related genes and regulated a broad set of lipid metabolism-related genes. In human hepatocellular carcinoma cell line HepG2 and human derived fetal hepatocyte cell line L02, givinostat significantly decreased palmitic acid-induced intracellular lipid accumulation. The benefit of givinostat was further confirmed in FPC-induced NASH mice. Givinostat administration significantly attenuated hepatic steatosis, inflammation as well as liver injury in this mouse model. In conclusion, givinostat is efficacious in reversing diet-induced NASH, and may serve as a therapeutic agent for the treatment of human NASH.},
	issn = {1745-7254},	url = {http://www.chinaphar.com/article/view/10533}
}