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Chenodeoxycholic Acid Derivative HS-1200 Inhibits Hepatocarcinogenesis and Improves Liver Function in
Miao Xu1, Qi Zhao2, Donghui Shao3
1Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China; Department of Gastroenterology, Jinan Hospital, Jinan, Shandong 250013, China.
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, and mutT 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.
