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Melatonin Ameliorates Liver Fibrosis Induced by Carbon Tetrachloride in Rats via Inhibiting TGF-β1/Smad Signaling Pathway

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Summary

Melatonin has been reported to inhibit hepatic fibrosis and the mechanism may be correlated to its anti-oxidant effect. Nevertheless, the mechanism is not completely identified. This study was conducted to investigate the effects of melatonin on TGF-β1/Smad signaling pathway in liver fibrosis in rats. The liver fibrosis model was made by the subcutaneous injection of CCl4. The liver pathology changes were detected using hematoxylin and eosin (H&E) staining and Van Gieson (VG) staining. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were measured with an autoanalyzer. Glutathione peroxidase (GPx) activities and levels of malondialdehyde (MDA) and hydroxyproline (Hyp) in liver were evaluated by spectrophotometry. Expression levels of TGF-β1, Smad2/3, phosphorylated Smad2/3 (p-Smad2/3) and Smad7 in liver were detected by immunohistochemistry and Western blot analysis. Results showed that melatonin suppressed CCl4-induced liver fibrosis, along with an improvement in histological changes, significant decreases in pathologic grading sores and obvious decreases in Hyp levels in liver. Melatonin improved liver function indicated by decreased serum ALT and AST activities. In addition, melatonin exerted its anti-oxidant effects, as supported by decreased MDA levels and increased GPx activities in liver. Furthermore, melatonin inhibited TGF-β1/Smad pathway, as evidenced by decreased TGF-β1, Smad2/3 and p-Smad2/3 expression and increased Smad7 expression in liver. In conclusion, melatonin may suppress CCl4-induced hepatic fibrosis in rats via inhibiting TGF-β1/Smad pathway. It is possible for melatonin to be a potential reagent to treat and cure liver fibrosis.

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Authors and Affiliations

  1. Department of Gastroenterology, First Affiliated Hospital of Anhui Medical University, Key Laboratory of Digestive Disease of Anhui Province, Hefei, 230022, China

    Yu-rong Wang, Ru-tao Hong, Yuan-yuan Xie & Jian-ming Xu

Authors
  1. Yu-rong Wang
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  2. Ru-tao Hong
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  3. Yuan-yuan Xie
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  4. Jian-ming Xu
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Corresponding author

Correspondence to Ru-tao Hong.

Additional information

This study was supported by the Natural Science Research Project of Colleges and Universities in Anhui Province (No. KJ2013A155) and the National Natural Science Foundation of China (No. 81370529).

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Wang, Yr., Hong, Rt., Xie, Yy. et al. Melatonin Ameliorates Liver Fibrosis Induced by Carbon Tetrachloride in Rats via Inhibiting TGF-β1/Smad Signaling Pathway. CURR MED SCI 38, 236–244 (2018). https://doi.org/10.1007/s11596-018-1871-8

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  • DOI: https://doi.org/10.1007/s11596-018-1871-8

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