title: The effect of ursodeoxycholic acid on oxidative stress level and DNase activity in rat liver after bile duct ligation.
abstract: Accumulation of hydrophobic bile acids (BAs) during cholestasis plays an important role in apoptosis initiation as well as oxidative stress increase in liver cells. Ursodeoxycholic acid (UDCA) acts as a protector in BA-induced cell injury.The aim of the study was to evaluate the effect of UDCA on oxidative stress level and DNase I and II activity caused by liver injury in bile duct ligation (BDL) rats.Wistar rats were divided in four groups: group 1, control (sham-operated); group 2, sham-operated and injected with UDCA (30 mg/kg); group 3,animals with BDL; and group 4,UDCA-treatedcholestatic rats. Animals were sacrificed after 9 days. Malondialdehyde (MDA; lipid peroxidation end-product) level and protein-molecule oxidative modification (carbonyl group content) significantly increased in BDL rat liver. Catalase (CAT) activity in liver tissue was found to be decreased in BDL rats. In addition, xanthine oxidase (XO) activity, which is thought to be one of the key enzymes producing reactive oxygen species, was found to be increased in the cholestatic group. The apoptotic effect in cholestasis was probably triggered by the increased activation of DNase I and II. The protective effect of UDCA on liver tissue damage in BDL rats, in comparison to cholestatic liver, were 1) decrease of MDA levels, 2) increased CAT activity, 3) reduced XO activity, and 4) effect on terminal apoptotic reaction, shown as a decrease in DNase I and II activity.Therefore, UDCA may be useful in the preservation of liver function in cholestasis treatment.
authors.affiliation: Department of Biochemistry, the University of Nis Medical School, Nis, Serbia. soko@medfak.ni.ac.rs
authors.forename: Dusan
authors.initials: D
authors.lastname: Sokolovic
authors.forename: Jelenka
authors.initials: J
authors.lastname: Nikolic
authors.forename: Gordana
authors.initials: G
authors.lastname: Kocic
authors.forename: Tatjana
authors.initials: T
authors.lastname: Jevtovic-Stoimenov
authors.forename: Andrej
authors.initials: A
authors.lastname: Veljkovic
authors.forename: Miroslav
authors.initials: M
authors.lastname: Stojanovic
authors.forename: Zoran
authors.initials: Z
authors.lastname: Stanojkovic
authors.forename: Danka M
authors.initials: DM
authors.lastname: Sokolovic
authors.forename: Marija
authors.initials: M
authors.lastname: Jelic
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D002756:Cholagogues and Choleretics / Q000494:pharmacology*; D001651:Cholestasis, Extrahepatic / Q000188:drug therapy* / Q000503:physiopathology; D003135:Common Bile Duct; D003850:Deoxyribonuclease I / Q000378:metabolism; D004195:Disease Models, Animal; D004706:Endodeoxyribonucleases / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*; D014969:Xanthine Oxidase / Q000378:metabolism
chemical_list: D002756:Cholagogues and Choleretics; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D014580:Ursodeoxycholic Acid; D002374:Catalase; D014969:Xanthine Oxidase; D004706:Endodeoxyribonucleases; D003850:Deoxyribonuclease I; C019329:deoxyribonuclease II