title: Chenodeoxycholic Acid Derivative HS-1200 Inhibits Hepatocarcinogenesis and Improves Liver Function in Diethylnitrosamine-Exposed Rats by Downregulating MTH1.
abstract: Aim. To investigate the effects of HS-1200 on liver tumorigenesis and liver function in a diethylnitrosamine- (DEN-) induced hepatocellular carcinoma (HCC) rat model.Methods. Rats were randomly assigned into five groups: control, HS-1200, HCC, HCC + low dose HS-1200, and HCC + high dose HS-1200 groups. Rat HCC model was established by intraperitoneal injection of DEN. And rats were given HS-1200 by daily oral gavage. After 20 weeks, we examined animal body weight, liver weight, liver pathological changes, serum levels of AST, ALT, and AFP, andmutT homologue gene 1 (MTH1)in liver tissue.Results. Oral gavage of HS-1200 significantly increased animal body weight and decreased liver weight as well as liver coefficient in HCC rats (P< 0.05 versus HCC group). Moreover, oral administration of HS-1200 suppressed tumorigenesis, attenuated pathological changes in liver tissues, and decreased serum levels of AST, ALT, and AFP in HCC rats (P< 0.05 versus HCC group). In addition, the mRNA level of MTH1 was upregulated in the liver tissues of HCC rats (P< 0.05 versus control group), which was reversed by HS-1200 treatment in a dose-dependent manner (P< 0.05 versus HCC group).Conclusions. HS-1200 inhibits hepatocarcinogenesis and improves liver function maybe by inducing downregulation of MTH1.
authors.affiliation: Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China; Department of Gastroenterology, Jinan Hospital, Jinan, Shandong 250013, China.
authors.forename: Miao
authors.identifier: 0000-0002-3074-0726
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Department of Gastroenterology, Jinan Hospital, Jinan, Shandong 250013, China.
authors.forename: Donghui
authors.identifier: 0000-0002-3162-6626
authors.initials: D
authors.lastname: Shao
authors.affiliation: Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Central Laboratory, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China.
authors.forename: Jianni
authors.initials: J
authors.lastname: Qi
authors.affiliation: Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China.
authors.forename: Chengyong
authors.identifier: 0000-0001-5431-3027
authors.initials: C
authors.lastname: Qin
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001835:Body Weight; D049109:Cell Proliferation; D002635:Chenodeoxycholic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000378:metabolism*; D004052:Diethylnitrosamine / Q000737:chemistry*; D015536:Down-Regulation; D005786:Gene Expression Regulation; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D009929:Organ Size; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D011755:Pyrophosphatases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
chemical_list: C479128:HS 1200; C000616635:Nudt1 protein, rat; D012333:RNA, Messenger; D002635:Chenodeoxycholic Acid; D004052:Diethylnitrosamine; D010744:Phosphoric Monoester Hydrolases; D011755:Pyrophosphatases; C078207:8-oxodGTPase; D045643:DNA Repair Enzymes