Oxidative stress and DNA fragmentation in hepatic injury of the bile duct-ligated rats: modulatory effect of ursodeoxycholic acid

Abstract

Event Abstract Back to Event Oxidative stress and DNA fragmentation in hepatic injury of the bile duct-ligated rats: modulatory effect of ursodeoxycholic acid Maja Jovic1, Marko Jovic1* and Dusan Sokolovic1 1 University of Nis, Institute of Biochemistry, Serbia Introduction. Accumulation of toxic hydrophobic bile acids (BA) during cholestasis can activate Fas death receptors directly and induce oxidative damage that causes mitochondrial dysfunction and hepatocyte apoptosis. Reactive oxygen species (ROS) induce chromatin dysfunction such as single- and double-strand DNA fragmentation. The major beneficial effects of treatment with ursodeoxycholic acid (UDCA) are protection against cytotoxicity of BA, stimulation of hepatobiliary secretion, antioxidative activity and blocking the apoptotic signal (inhibition of mitochondrial cytochrome C releasing). Aim of the present study was to evaluate the effect of UDCA on oxidative stress and DNA fragmentation in liver injury of bile duct-ligated (BDL) rats. Material and Methods. Three groups of Wistar rats were investigated: I-sham-operated, II-BDL and III-BDL+UDCA (30mg/kgBW,i.g.). The animals were killed after 7 days. Results: Lipid peroxidation (MDA) level and oxidative modification of proteins (carbonyl group content) significantly increased in BDL group (4.75±0.59 vs. sham-operated 2.84±0.31 nmol/mg prot, p<0.001 and 48.21±6.37 vs. sham-operated 39.63±5.69µmol/g prot,p<0.05). Activity of catalase, the free radicals scavenging enzymes was decreased in liver of BDL rats (5.8±2.11 vs. sham-operated 8.4±2.05 U/mg prot,p<0.001). Xanthine oxidase (XO), major enzyme of ROS production was increased in cholestatic group (2.25±0.26 vs. sham-operated 1.48±0.46 U/g prot;p<0.001). The apoptotic effect in cholestasis is probably triggered by the increase activation of alkaline-DNase I (caspase 3-activated) and acid-DNase II (3.19±0.61 vs. sham-operated 1.06±0.19 U/g prot. and 2.93±0.91 vs. sham-operated 1.53±0.24 U/g prot,p<0.001). UDCA was found to be effective in liver of BDL rats:(1) decreased MDA levels (3.26±0.67,p<0.01),(2) no significantly decreased carbonyl group (45.62±6.69), (3) increase activity of catalase (7.94±1.34, p<0.001), (4) reduces activity of XO (1.77±0.68,p<0.05). (5) effect on terminal apoptotic reaction, because of the decrease in DNase I and DNase II activity (2.37±0.34 and 1.92±0.42,p<0.05), compared with cholestatic liver. Conclusion. These results support a novel effect for UDCA in the control of endonuclease activity as a final down-stream mediator of apoptosis and therefore in the DNA stability, beside established role in reducing oxidative damage and maintained antioxidant defenses in cholestatic liver. Keywords: Cholestasis, Oxidative Stress, Ursodeoxycholic Acid, DNA, Rats Conference: 8th Southeast European Congress on Xenobiotic Metabolism and Toxicity - XEMET 2010, Thessaloniki, Greece, 1 Oct - 5 Oct, 2010. Presentation Type: Poster Topic: Xenobiotic toxicity Citation: Jovic M, Jovic M and Sokolovic D (2010). Oxidative stress and DNA fragmentation in hepatic injury of the bile duct-ligated rats: modulatory effect of ursodeoxycholic acid. Front. Pharmacol. Conference Abstract: 8th Southeast European Congress on Xenobiotic Metabolism and Toxicity - XEMET 2010. doi: 10.3389/conf.fphar.2010.60.00133 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 28 Oct 2010; Published Online: 04 Nov 2010. * Correspondence: Dr. Marko Jovic, University of Nis, Institute of Biochemistry, Nis, Serbia, markojovic10@yahoo.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Maja Jovic Marko Jovic Dusan Sokolovic Google Maja Jovic Marko Jovic Dusan Sokolovic Google Scholar Maja Jovic Marko Jovic Dusan Sokolovic PubMed Maja Jovic Marko Jovic Dusan Sokolovic Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.