Inhibitory effect of flufenidone on TGF-β1/Smads pathway in hepatocytes of rats with diethylnitrosamine (DEN)-induced liver injury
10.12092/j.issn.1009-2501.2022.07.003
- Author:
Feng WEI
1
;
Yang HE
1
;
Zhiqiang FAN
1
;
Linqi OUYANG
1
;
Shikun LIU
2
;
Linqi OUYANG
3
Author Information
1. Department of Pharmacy, The First Hospital of Hunan University of Chinese Medicine
2. Department of Pharmacy, The Third Xiangya Hospital of Central South University
3. School of Pharmacy, Hunan University of Chinese Medicine
- Publication Type:Journal Article
- Keywords:
flufenidone;
hepatocytes;
liver fibrosis;
TGF-β1/Smads pathway
- From:
Chinese Journal of Clinical Pharmacology and Therapeutics
2022;27(7):739-746
- CountryChina
- Language:Chinese
-
Abstract:
AIM: To explore the protective effect of fluorofenidone (AKF-PD) on diethylnitrosamine-induced liver injury in rats and its inhibition of the TGF-β1/Smads pathway in hepatocytes. METHODS: Fifty-five male Sprague Dawley (SD) rats were randomly divided into three groups: model group (DEN group, n=20) were gavaged with DEN (10 mg/kg), 5 times for 14 weeks; control group (n=20) were gavaged with saline with the same volume of the model group; treatment group (DEN+AKF-PD Group, n=15), after 4 weeks of modeling, they were gavaged with AKF-PD (500 mg/kg) daily, and stopped at 14 weeks. At the end of experiment, the rats were killed by anesthesia and spinal dislocation. Masson staining was used to observe collagen deposition; primary hepatocytes were extracted and identified, and the levels of α-smooth muscle actin (α-SMA), TGF-β1, Smad3, and Smad7 mRNA, and the expression of Smad3 and Smad7 proteins in hepatocytes were detected. RESULTS: Compared with the control group, Masson staining showed that collagen deposition increased in the DEN group; AKF-PD treatment could significantly improve liver pathological damage and reduce collagen deposition. In addition, compared with the DEN group, the α-SMA, TGF-β1, and Smad3 mRNA levels of the AKF-PD group were significantly reduced, and the Smad7 mRNA level was increased. Moreover, AKF-PD treatment could dependably reduce the expression of Smad3 and increase Smad7. CONCLUSION: AKF-PD can significantly improve liver injury and fibrosis in rats caused by DEN. This effect may be related to the down-regulation of α-SMA, TGF-β1, and Smad3 mRNA levels in hepatocytes and the increase of Smad7 mRNA levels.
