Oxidative stress and Liver X Receptor agonist induce hepatocellular carcinoma in Non-alcoholic steatohepatitis model.
J Gastroenterol Hepatol
; 36(3): 800-810, 2021 Mar.
Article
in En
| MEDLINE
| ID: mdl-32870526
ABSTRACT
BACKGROUND AND AIM:
The incidence of non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC) is progressively increasing. However, the pathophysiology and etiology of NASH progression to HCC are unknown. We hypothesized that steatosis was the key factor in NASH-related hepatocarcinogenesis and aimed to evaluate the effects of long-term liver X receptor (LXR) agonist stimulation on hepatic steatosis induced by a high-fat diet and oxidative stress.METHODS:
We used an LXR agonist (T0901317) and CCl4 to induce hepatic steatosis and oxidative stress, respectively. C57BL/6 mice fed with a high-fat diet were treated with either T0901317 + CCl4 (T09 + CCl4 group) or CCl4 alone (CCl4 group). T0901317 (2.5 mg/kg) and CCl4 (0.1 mL/kg) were intraperitoneally administered twice weekly for 24 weeks.RESULTS:
The liver-to-body weight ratio was significantly higher in the T09 + CCl4 group than in the CCl4 group. Mice in the T09 + CCl4 group exhibited abnormal lipid metabolism and NASH-like histopathological features. Additionally, all mice in the T09 + CCl4 group developed liver tumors diagnosed as well-differentiated HCC. The genes identified via microarray analysis were related to NASH and HCC development.CONCLUSIONS:
By combining long-term LXR agonist stimulation with oxidative stress and a high-fat diet, we successfully reproduced liver conditions in mice similar to those in humans with NASH and progression to HCC. Our results provide new insight into NASH-related HCC progression and therapy.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sulfonamides
/
Carcinoma, Hepatocellular
/
Oxidative Stress
/
Non-alcoholic Fatty Liver Disease
/
Liver X Receptors
/
Hydrocarbons, Fluorinated
/
Liver Neoplasms
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
J Gastroenterol Hepatol
Journal subject:
GASTROENTEROLOGIA
Year:
2021
Type:
Article
Affiliation country:
Japan