Trichostatin A protects against intestinal injury in rats with acute liver failure.
Histone deacetylase (HDAC) inhibitors have been widely applied in the clinic as anticancer drugs against multiple neoplasms and proved their anti-inflammation under different pathology recently. Trichostatin A (TSA) is an HDAC inhibitor specific in class I and II HDAC enzymes. The aim of the present study was to elucidate the protective effects of TSA on acute liver failure (ALF) in rats and its potential mechanism.



A total of 18 female Sprague-Dawley rats were separated into control, model, and TSA groups. We used Western blotting to determine the expression of HDACs, inflammatory cytokines, and acetylation of histone in liver and small intestine. The gene expression of inflammatory factors and Cox-2 was detected by a polymerase chain reaction. Colonic motility was assessed by spatiotemporal mapping. Histologic analysis and immunohistochemistry were performed. Intestinal permeability examination and levels of alanine aminotransferase, aspartate aminotransferase, and total bilirubin were also observed.



ALF procedure caused harm to histology of liver and small intestine, increased the intestinal permeability and serum levels of alanine aminotransferase, aspartate aminotransferase, and total bilirubin. It also interrupted the normal organization of colonic motor patterns by hurting enteric nervous system and pacemaker cells. Along with the decrease of inflammatory factors in ALF rats by TSA administration, all the damage to the liver, the small intestine, and the colon was repaired.



TSA alleviates the lesion in liver, as well as in small intestine and colon in ALF rats by directly inhibiting inflammatory response.
Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, China.
Qian
Q
Zhang
Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, China.
Fan
F
Yang
Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, China.
Xun
X
Li
Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, China.
Hai-Yue
HY
Zhang
Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, China.
Xiao-Gang
XG
Chu
Pharmaceutical ​Department, Renmin Hospital of Wuhan University, Wuhan, China.
Hong
H
Zhang
Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, China.
Lu-Wen
LW
Wang
Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, China. Electronic address: zjgong@163.com.
Zuo-Jiong
ZJ
Gong
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use*; D006655:Histone Deacetylases / Q000378:metabolism; D006877:Hydroxamic Acids / Q000627:therapeutic use*; D007410:Intestinal Diseases / Q000209:etiology / Q000517:prevention & control*; D007421:Intestine, Small / Q000187:drug effects; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D017114:Liver Failure, Acute / Q000150:complications* / Q000201:enzymology / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D016207:Cytokines; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D008070:Lipopolysaccharides; C012589:trichostatin A; D006655:Histone Deacetylases
Endotoximia; Histone deacetylase inhibitor; Inflammatory factors; Intestinal permeability