The protective effect of resveratrol on dimethylnitrosamine-induced liver fibrosis in rats
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Oxidative stress in liver injury is a major pathogenetic factor in progress of liver fibrosis. Resveratrol, a representative antioxidant derived from grapes, has been reported to show widespread pharmacological properties. In this study, we investigated the protective effects of resveratrol on dimethylnitrosamine (DMN)-induced liver fibrosis in rats. Rats were treated with resveratrol daily by oral gavage for seven days after a single intraperitoneal injection of DMN (40 mg/kg). Resveratrol remarkably recovered body and liver weight loss due to DMNinduced liver fibrosis. Liver histology showed that resveratrol alleviated the infiltration of inflammatory cells and fibrosis of liver tissue. Resveratrol decreased the level of malondialdehyde and increased the levels of glutathione peroxidase and superoxide dismutase. Also, resveratrol significantly inhibited the mRNA expression of inflammatory mediators including inducible nitric oxide, tumor necrosis factor-alpha and interleukin-1beta. In addition, resveratrol showed not only reduced mRNA expression of fibrosis-related genes such as transforming growth factor beta 1, collagen type I, and alpha-smooth muscle actin, but also a significant decrease of hydroxyproline in rats with DMN-induced liver fibrosis. Our results suggest that resveratrol could be used to treat liver injury and fibrosis and be useful in preventing the development of liver fibrosis and cirrhosis.
Key wordsLiver injury Resveratrol Antioxidant enzyme TGF-β1 Collagen type I α-SMA
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- Birrell, M. A., McCluskie, K., Wong, S., Donnelly, L. E., Barnes, P. J., and Belvisil, M. G., Resveratrol, an extract of red wine, inhibits lipopolysaccharide induced airway neutrophilia and inflammatory mediators through an NFkappa B-independent mechanism. FASEB J., 19, 840–841 (2005).PubMedGoogle Scholar
- Bisht, K., Wagner, K. H., and Bulmer, A. C., Curcumin, resveratrol and flavonoids as anti-inflammatory, cyto- and DNA-protective dietary compounds. Toxicology, Epub ahead of print (2009).Google Scholar
- Cai, Y. J., Fang, J. G., Ma, L. P., Yang, L., and Liu, Z. L., Inhibition of free radical-induced peroxidation of rat liver microsomes by resveratrol and its analogues. Biochim. Biophys. Acta, 1637, 313–318 (2003).Google Scholar
- Chavez, E., Reyes-Gordillo, K., Segovia, J., Shibayama, M., Tsutsumi, V., Vergara, P., Moreno, M. G., and Muriel, P., Resveratrol prevents fibrosis, NF-kappa B activation and TGF-beta increases induced by chronic CCl4 treatment in rats. J. Appl. Toxicol., 28, 35–43 (2008).CrossRefPubMedGoogle Scholar
- Chen, A. and Zhang, L., The antioxidant (-)-epigallocatechin-3-gallate inhibits rat hepatic stellate cell proliferation in vitro by blocking the tyrosine phosphorylation and reducing the gene expression of platelet-derived growth factorbeta receptor. J. Biol. Chem., 278, 23381–23389 (2003).CrossRefPubMedGoogle Scholar
- Ezquerro, I. J., Lasarte, J. J., Dotor, J., Castilla-Cortazar, I., Bustos, M., Penuelas, I., Blanco, G., Rodriguez, C., Lechuga Mdel, C., Greenwel, P., Rojkind, M., Prieto, J., and Borras-Cuesta, F., A synthetic peptide from transforming growth factor beta type III receptor inhibits liver fibrogenesis in rats with carbon tetrachloride liver injury. Cytokine, 22, 12–20 (2003).CrossRefPubMedGoogle Scholar
- Hierholzer, C., Harbrecht, B., Menezes, J. M., Kane, J., Macmicking, J., Nathan, C. F., Peitzman, A. B., Billiar, T. R., and Twardy, D. J., Essential role of induced nitric oxide in the initiation of the inflammatory response after hemorrhagic shock. J. Exp. Med., 187, 917–928 (1998).CrossRefPubMedGoogle Scholar
- Ohara, F., Nii, A., Sakiyama, Y., Tsuchiya, M., and Ogawa, S., Pathophysiological characteristics of dimethylnitrosamine-induced liver fibrosis in acute and chronic injury models: a possible contribution of KLF5 to fibrogenic responses. Dig. Dis. Sci., 53, 2222–2232 (2008).CrossRefPubMedGoogle Scholar