title: Protective effects of Mg-CUD against D-galactosamine-induced hepatotoxicity in rats.
abstract: This study examined the protective effects of magnesium chenoursodeoxycholic acid (Mg-CUD), a magnesium trihydrate salt of chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA), against D-galactosamine (D-GalN)-induced liver injury. Hepatotoxicity was induced by intraperitoneal injection of D-GalN (700mg/kg) and Mg-CUD (15.625, 31.25 and 62.5mg/kg) was administered orally once a day for 2weeks and 6h after D-GalN injection. Significant increases in the level of serum alanine aminotransferase activity and lipid peroxidation were attenuated by Mg-CUD 24h after D-GalN treatment. Hepatic glutathione/oxidized glutathione ratio was decreased, and this decrease was attenuated by Mg-CUD. Mg-CUD attenuated the increase in the levels of serum tumor necrosis factor (TNF)-α and interleukin (IL)-6, while it augmented the increase in serum IL-10 level and heme oxygenase (HO)-1 protein expression. Mg-CUD attenuated increased levels of TNF-α, IL-6, and IL-1β mRNA expression. Increased levels of IL-10 and HO-1 mRNA expression were augmented by Mg-CUD. The increased nuclear level of nuclear factor-κB (NF-κB) and decreased cytosolic level of Inhibitory κB-α protein were attenuated by Mg-CUD. Nuclear phosphorylated c-Jun (p-c-Jun) level showed a significant increase and this increase was attenuated by Mg-CUD. Our results suggest that Mg-CUD ameliorates D-GalN-induced acute hepatitis and that this protection is likely due to its anti-oxidative and anti-inflammatory activities, and inhibition of NF-κB nuclear translocation and nuclear p-c-Jun expression.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon, Gyeonggi-do 440-746, Republic of Korea.
authors.forename: Jun-Ho
authors.initials: JH
authors.lastname: Choi
authors.forename: Jung-Woo
authors.initials: JW
authors.lastname: Kang
authors.forename: Dong-Wook
authors.initials: DW
authors.lastname: Kim
authors.forename: Yong-Kyung
authors.initials: YK
authors.lastname: Sung
authors.forename: Sun-Mee
authors.initials: SM
authors.lastname: Lee
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D005688:Galactosamine / Q000633:toxicity*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D019803:Glutathione Disulfide / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009942:Organometallic Compounds / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000637:Transaminases / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*
chemical_list: D015850:Interleukin-6; D016328:NF-kappa B; D009942:Organometallic Compounds; D010750:Phosphoproteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C559096:magnesium chenoursodeoxycholic acid; D016753:Interleukin-10; D014580:Ursodeoxycholic Acid; D005688:Galactosamine; D051547:Heme Oxygenase-1; D000637:Transaminases; D051550:I-kappa B Kinase; D048031:JNK Mitogen-Activated Protein Kinases; D019803:Glutathione Disulfide