Vitamin E Succinate Enhances Steatotic Liver Energy Status and Prevents Oxidative Damage Following Ischemia/Reperfusion

• Published in: Transplantation proceedings Vol. 41; no. 10; pp. 4094 - 4098
• Main Authors: Evans, Z.P, Mandavilli, B.S, Ellett, J.D, Rodwell, D, Fariss, M.W, Fiorini, R.N, Schnellmann, R.G, Schmidt, M.G, Chavin, K
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2009
• Subjects: Animals; Blotting, Northern; DNA Damage; DNA, Mitochondrial - genetics; Fatty Liver - metabolism; Fatty Liver - pathology; Glutathione - metabolism; Ion Channels - genetics; Leptin - deficiency; Liver - drug effects; Liver - metabolism; Liver - physiopathology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Obese; Mitochondrial Proteins - genetics; Reperfusion Injury - prevention & control; RNA, Messenger - genetics; Succinates - pharmacology; Surgery; Uncoupling Protein 2; Vitamin E - pharmacology
• ISSN: 0041-1345; 1873-2623
• DOI: 10.1016/j.transproceed.2009.09.055

Abstract We have previously shown that treatment of steatotic livers with vitamin E succinate decreases liver injury and increases survival after ischemia/reperfusion (I/R). It is now understood that compromised energy status is associated with increased injury following liver ischemia in the setting of hepatic steatosis at least partially as a result of increased reactive oxygen species (ROS) and induction of mitochondrial uncoupling protein-2 (UCP2). Given the association between ROS, mitochondrial function, and UCP2, it was our goal to determine whether the protective effects of vitamin E succinate were associated with decreased ROS injury, down-regulation of UCP2, or improvement of ATP levels following I/R. To test this, leptin deficient (ob/ob) mice with steatotic livers that had received other 50 IU of vitamin E succinate supplement per day or control chow for 7 days were subjected to total hepatic ischemia (15 minutes) followed by reperfusion. We measured liver expressions of ATP, glutathione (GSH), and UCP2 as well as mitochondrial DNA damage. Vitamin E treatment decreased hepatic UCP2 expression and increased ATP and GSH levels prior to I/R. These levels were maintained at 1 hour after I/R. At 24 hours, while hepatic UCP2 expression, ATP, and GSH levels were similar to those of mice not receiving vitamin E, mitochondrial DNA damage was blocked. These results revealed that vitamin E succinate decreased hepatic UCP2 expression, reduced oxidative stress, and improved mitochondrial function in mice with steatotic livers before and after I/R, identifying mechanisms of protection in this setting.