title: Magnesium chenoursodeoxycholic acid ameliorates carbon tetrachloride-induced liver fibrosis in rats.
abstract: This study was designed to investigate the hepatoprotective effects of magnesium chenoursodeoxycholic acid (Mg-CUD), a magnesium trihydrate salt of ursodeoxycholic acid and chenodeoxycholic acid, in carbon tetrachloride (CCl(4))-induced liver fibrosis in rats. Rats were treated with CCl(4) dissolved in olive oil (0.5 mL/kg, twice a week) intraperitoneally for eight weeks. Mg-CUD was administered orally at 15.625, 31.25, 62.5 and 125 mg/kg once a day. Chronic CCl(4) administration induced increases in serum transforming growth factor-β1, hepatic hydroxyproline content and serum alanine aminotransferase activity. Mg-CUD attenuated these increases. The levels of α-smooth muscle actin protein and mRNA expression were increased by chronic CCl(4) exposure and Mg-CUD attenuated these increases. Mg-CUD suppressed increases in matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 mRNA expression and elevation of oxidative stresses by attenuating lipid peroxidation and enhancing reduced glutathione/oxidized glutathione ratio. The overexpression of toll-like receptor 4 and increased nuclear translocation of nuclear factor-κB and phosphorylated c-Jun, a component of activator protein 1, were suppressed by Mg-CUD. Furthermore, CCl(4) increased the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10 and cyclooxygenase (COX)-2. Mg-CUD attenuated the levels of TNF-α, IL-6 and COX-2, while it augmented the level of IL-10. Our results suggest that Mg-CUD may prevent liver fibrosis by modulating collagen accumulation and inflammatory signaling pathways.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon Gyeonggi-do 440-746, Republic of Korea.
authors.forename: Jung-Woo
authors.initials: JW
authors.lastname: Kang
authors.forename: Seong-Jin
authors.initials: SJ
authors.lastname: Yoon
authors.forename: Yong-Kyung
authors.initials: YK
authors.lastname: Sung
authors.forename: Sun-Mee
authors.initials: SM
authors.lastname: Lee
mesh_terms: D000199:Actins / Q000096:biosynthesis; D000410:Alanine Transaminase / Q000096:biosynthesis / Q000097:blood; D000818:Animals; D002251:Carbon Tetrachloride; D002252:Carbon Tetrachloride Poisoning / Q000188:drug therapy*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006909:Hydroxyproline / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D016328:NF-kappa B / Q000096:biosynthesis; D009942:Organometallic Compounds / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000199:Actins; D015850:Interleukin-6; D016328:NF-kappa B; D009942:Organometallic Compounds; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D051197:Toll-Like Receptor 4; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; C559096:magnesium chenoursodeoxycholic acid; D016753:Interleukin-10; D002251:Carbon Tetrachloride; D051546:Cyclooxygenase 2; D000410:Alanine Transaminase; D048031:JNK Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2; D005978:Glutathione; D006909:Hydroxyproline