l-Theanine prevents carbon tetrachloride-induced liver fibrosis via inhibition of nuclear factor κB and down-regulation of transforming growth factor β and connective tissue growth factor

• Published in: Human & experimental toxicology 2016-02, Vol.35 (2), p.135-146
• Main Authors: Pérez-Vargas, JE, Zarco, N, Vergara, P, Shibayama, M, Segovia, J, Tsutsumi, V, Muriel, P
• Format: Article
• Language: English
• Subjects: Alanine Transaminase - blood; Animals; Antioxidants - metabolism; Aspartate Aminotransferases - blood; Carbon Tetrachloride Poisoning - pathology; Carbon Tetrachloride Poisoning - prevention & control; Chemical and Drug Induced Liver Injury - pathology; Chemical and Drug Induced Liver Injury - prevention & control; Connective Tissue Growth Factor - biosynthesis; Connective Tissue Growth Factor - drug effects; Cytokines - biosynthesis; Down-Regulation - genetics; Glutamates - therapeutic use; Lipid Peroxidation - drug effects; Liver Cirrhosis - chemically induced; Liver Cirrhosis - pathology; Liver Cirrhosis - prevention & control; Male; Matrix Metalloproteinase 13 - biosynthesis; NF-kappa B - biosynthesis; NF-kappa B - drug effects; Rats; Rats, Wistar; Transforming Growth Factor beta - biosynthesis; Transforming Growth Factor beta - drug effects
• ISSN: 0960-3271; 1477-0903
• DOI: 10.1177/0960327115578864

Here we evaluated the ability of l-theanine in preventing experimental hepatic cirrhosis and investigated the roles of nuclear factor-κB (NF-κB) activation as well as transforming growth factor β (TGF-β) and connective tissue growth factor (CTGF) regulation. Experimental hepatic cirrhosis was established by the administration of carbon tetrachloride (CCl4) to rats (0.4 g/kg, intraperitoneally, three times per week, for 8 weeks), and at the same time, adding l-theanine (8.0 mg/kg) to the drinking water. Rats had ad libitum access to water and food throughout the treatment period. CCl4 treatment promoted NF-κB activation and increased the expression of both TGF-β and CTGF. CCl4 increased the serum activities of alanine aminotransferase and γ-glutamyl transpeptidase and the degree of lipid peroxidation, and it also induced a decrease in the glutathione and glutathione disulfide ratio. l-Theanine prevented increased expression of NF-κB and down-regulated the pro-inflammatory (interleukin (IL)-1β and IL-6) and profibrotic (TGF-β and CTGF) cytokines. Furthermore, the levels of messenger RNA encoding these proteins decreased in agreement with the expression levels. l-Theanine promoted the expression of the anti-inflammatory cytokine IL-10 and the fibrolytic enzyme metalloproteinase-13. Liver hydroxyproline contents and histopathological analysis demonstrated the anti-fibrotic effect of l-theanine. In conclusion, l-theanine prevents CCl4-induced experimental hepatic cirrhosis in rats by blocking the main pro-inflammatory and pro-fibrogenic signals.