Melatonin Alleviates Liver Fibrosis by Inhibiting Autophagy

Abstract

Objective

Melatonin has been reported to suppress inflammation and alleviate liver fibrosis, but its effect on autophagy in liver fibrosis has not been studied. This study investigated the effect of melatonin on autophagy in an animal model of liver fibrosis and the hepatic stellate cell (HSC)-T6 cell line.

Methods

The model was established in rats through carbon tetrachloride treatment, and melatonin was administered at three doses (2.5, 5.0, and 10.0 mg/kg). Haematoxylin and eosin staining and Van Gieson’s staining were performed to examine the pathological changes of liver. The expression of alpha-smooth muscle actin (α-SMA) and Beclin1 in liver tissues was detected by immunohistochemical staining. The protein levels of α-SMA, Beclin1 and LC3 in the animal model were detected by Western blot analysis, and gene levels of Beclin1 and LC3 were detected by quantitative real-time PCR (qRT-PCR) in the animal model. HSC-T6 cells were activated by platelet-derived growth factor-BB (PDGF-BB). The expression of α-SMA, Beclin1 and collagen I was detected by Western blot analysis, and the gene expression of Beclin1 and LC3 was detected by qRT-PCR.

Results

Melatonin reduced the expression of α-SMA, Beclin1 and LC3 in liver tissues. In addition, melatonin inhibited the activation of HSC-T6 cells and the expression of α-SMA, Beclin1 and LC3 in these cells. These results revealed that melatonin could inhibit autophagy and HSC activation.

Conclusion

Melatonin might ameliorate liver fibrosis by regulating autophagy, suggesting that melatonin is a potential therapeutic agent for liver fibrosis.

Keywords

autophagy / liver fibrosis / hepatic stellate cells / melatonin

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