title: 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.
abstract: 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.
authors: Department of Pharmacology, Cinvestav-IPN Apartado, D.F. México.
authors: J E
authors: JE
authors: Pérez-Vargas
authors: Department of Physiology, Biophysics and Neurosciences, Cinvestav-IPN Apartado, D.F. México.
authors: N
authors: N
authors: Zarco
authors: Department of Physiology, Biophysics and Neurosciences, Cinvestav-IPN Apartado, D.F. México.
authors: P
authors: P
authors: Vergara
authors: Department of Infectomics and Molecular Pathogenesis, Cinvestav-IPN Apartado, D.F. México.
authors: M
authors: M
authors: Shibayama
authors: Department of Physiology, Biophysics and Neurosciences, Cinvestav-IPN Apartado, D.F. México.
authors: J
authors: J
authors: Segovia
authors: Department of Infectomics and Molecular Pathogenesis, Cinvestav-IPN Apartado, D.F. México.
authors: V
authors: V
authors: Tsutsumi
authors: Department of Pharmacology, Cinvestav-IPN Apartado, D.F. México pmuriel@cinvestav.mx.
authors: P
authors: P
authors: Muriel
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000097:blood; D002252:Carbon Tetrachloride Poisoning / Q000473:pathology* / Q000517:prevention & control*; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology* / Q000517:prevention & control*; D055513:Connective Tissue Growth Factor / Q000096:biosynthesis* / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D015536:Down-Regulation / Q000235:genetics; D005971:Glutamates / Q000627:therapeutic use*; D015227:Lipid Peroxidation / Q000187:drug effects; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control*; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis; D016328:NF-kappa B / Q000096:biosynthesis* / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000187:drug effects
chemical_list: D000975:Antioxidants; D016207:Cytokines; D005971:Glutamates; D016328:NF-kappa B; D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor; C026166:theanine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D053509:Matrix Metalloproteinase 13
keywords: NF-κB; carbon tetrachloride; cirrhosis; cytokines; l-Theanine; liver damage; necrosis; oxidative stress