Vitamin E succinate enhances steatotic liver energy status and prevents oxidative damage following ischemia/reperfusion.
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.
Evans
Z P
ZP
Department of Transplant Surgery, Medical University of South Carolina, South Carolina, USA.
Mandavilli
B S
BS
Ellett
J D
JD
Rodwell
D
D
Fariss
M W
MW
Fiorini
R N
RN
Schnellmann
R G
RG
Schmidt
M G
MG
Chavin
K
K
D000818:Animals; D015152:Blotting, Northern; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000235:genetics; D005234:Fatty Liver / Q000378:metabolism* / Q000473:pathology; D005978:Glutathione / Q000378:metabolism; D007473:Ion Channels / Q000235:genetics; D020738:Leptin / Q000172:deficiency; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D024101:Mitochondrial Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D015427:Reperfusion Injury / Q000517:prevention & control*; D013386:Succinates / Q000494:pharmacology; D000071246:Uncoupling Protein 2; D014810:Vitamin E / Q000494:pharmacology*
D004272:DNA, Mitochondrial; D007473:Ion Channels; D020738:Leptin; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D013386:Succinates; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2; D014810:Vitamin E; D005978:Glutathione