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European Journal of Gastroenterology & Hepatology:
doi: 10.1097/MEG.0b013e3283644e26
Original Articles: Liver Fibrosis

Caffeine prevents experimental liver fibrosis by blocking the expression of TGF-β

Arauz, Jonathana; Zarco, Natanaelb; Segovia, Joséb; Shibayama, Minekoc; Tsutsumi, Victorc; Muriel, Pabloa

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Abstract

Background

There is a growing body of evidence that caffeine exerts beneficial effects on the liver; however, the molecular mechanisms by which caffeine exerts beneficial effects on the liver are poorly defined.

Aims

The aim of the present study was to examine the efficacy of caffeine in preventing thioacetamide (TAA)-induced cirrhosis in rats.

Materials and methods

Cirrhosis was induced by chronic TAA administration and the effects of coadministration of caffeine for 8 weeks were evaluated, including control groups.

Results

The administration of TAA induced liver cirrhosis, which was inhibited by caffeine. Caffeine prevents elevation of liver enzymes. Liver histopathology and hydroxyproline levels were significantly lower in the rats treated with TAA plus caffeine compared with TAA only. Caffeine shows antioxidant properties by restoring the redox equilibrium [lipid peroxidation and glutathione peroxidase (GPx) levels]. Western blot assays showed blockade of the expression of transforming growth factor-β and its downstream inductor connective tissue growth factor. Similarly, caffeine decreases messenger RNA levels of these profibrogenic proteins. In addition, caffeine inhibits hepatic stellate cells because of blockade of the expression of α-smooth muscle actin; in the western blot assay, we also found low levels of mRNA of collagen α1. Zymography assays showed that caffeine had an effect on the activity of matrix metalloproteinases 2 and 9, but no effect on the expression of tissue inhibitor of metalloproteinases-1, using RT-PCR.

Conclusion

Our results show that caffeine prevents experimental cirrhosis; the mechanisms of action are associated with its antioxidant properties and mainly by its ability to block the elevation of the profibrogenic cytokine transforming growth factor-β, which may be associated with attenuation of the inflammatory and fibrotic processes.

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins

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