title: Sulfasalazine prevents the increase in TGF-β, COX-2, nuclear NFκB translocation and fibrosis in CCl4-induced liver cirrhosis in the rat.
abstract: It has been demonstrated that this sulfasalazine (SF) inhibits the nuclear factor κB (NFκB) pathway, which regulates important genes during inflammation and immune answer. The aim of this work was to evaluate the effects of SF on carbon tetrachloride (CCl(4))-induced liver fibrosis. We formed the following experimental groups of rats: controls, damage induced by chronic CCl(4) (0.4 g/kg, intraperitoneally, three times a week for 8 weeks) administration and CCl(4) + SF (100 mg/kg/day, postoperatively for 8 weeks) administration. We determined the activities of alanine aminotransferase (ALT), γ-glutamyl transpeptidase (γ-GTP), cyclooxygenase (COX)-1 and COX-2, lipid peroxidation, glutathione levels, collagen content, expression of transforming growth factor-β (TGF-β) and nuclear translocation of NFκB. SF was capable to inhibit the ALT and γ-GTP elevated levels induced with the CCl(4) administration. SF had antioxidant properties, prevented the lipid peroxidation and the imbalance of reduced and oxidized glutathione produced by CCl(4). Importantly, SF blocked the accumulation of collagen in the liver, the expression of TGF-β, the nuclear translocation of NFκB and the activity of COX-2, all induced with the administration of CCl(4) in the rat. These results show that SF has strong antifibrotic properties because of its antioxidant properties and its ability to prevent nuclear translocation of NFκB and consequently the expression of TGF-β and the activity of COX-2.
authors.affiliation: Departamento de Farmacología, Cinvestav-IPN, Apdo, México, DF México.
authors.forename: E
authors.initials: E
authors.lastname: Chávez
authors.forename: L
authors.initials: L
authors.lastname: Castro-Sánchez
authors.forename: M
authors.initials: M
authors.lastname: Shibayama
authors.forename: V
authors.initials: V
authors.lastname: Tsutsumi
authors.forename: M G
authors.initials: MG
authors.lastname: Moreno
authors.forename: P
authors.initials: P
authors.lastname: Muriel
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D002251:Carbon Tetrachloride; D003094:Collagen / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012460:Sulfasalazine / Q000494:pharmacology / Q000627:therapeutic use*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D016328:NF-kappa B; D016212:Transforming Growth Factor beta; D012460:Sulfasalazine; D003094:Collagen; D002251:Carbon Tetrachloride; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D005723:gamma-Glutamyltransferase; D000410:Alanine Transaminase; D005978:Glutathione; D019803:Glutathione Disulfide