c-fos and c-jun mRNA expression in a pig liver model of ischemia/reperfusion: effect of extended cold storage and the antioxidant idebenone.
OBJECTIVE
Expression of immediate early genes has been reported during reperfusion after ischemia in rat livers due to oxygen radical formation. This study investigates in perfused pig livers the effect of the antioxidant idebenone and of cold ischemia time on the gene expression of c-fos and c-jun.


METHODS
Livers were perfused for 210 min after 0.5 h or 20 h ischemic storage (4 degrees C). One group of pigs was fed idebenone (280 mg/day/7days) prior to organ harvesting. C-fos and c-jun mRNA were determined by RT-PCR at 3, 30, 60, 120 180, 210 min during reperfusion.


RESULTS
Lipid peroxidation increased in liver tissue form 0.54 +/- 0.21 to 1. 09 +/- 0.54 nmol MDA/mg protein during reperfusion after 20 h compared to 0.5 h cold storage. This was antagonized by idebenone (0. 68 +/- 0.20 nmol/MDA/mg protein). C-fos and c-jun were strongly induced in livers stored for 20 h, which was attenuated by idebenone (p < 0.05).


CONCLUSIONS
These findings suggest that cold ischemia time and oxygen radicals are critical for immediate early gene expression and that application of an effective antioxidant can attenuate this early stress reaction of the pig liver.
Wieland
E
E
Abteilung Klinische Chemie, Georg-August-Universität, Göttingen, Germany. ewieland@med.uni-goettingen.de
Oellerich
M
M
Braun
F
F
Schtüz
E
E
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D016227:Benzoquinones / Q000494:pharmacology*; D003080:Cold Temperature; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D016762:Genes, fos; D016758:Genes, jun; D006801:Humans; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D016031:Liver Transplantation; D008297:Male; D015394:Molecular Structure; D010477:Perfusion; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics; D051381:Rats; D015427:Reperfusion Injury / Q000188:drug therapy / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014451:Ubiquinone / Q000031:analogs & derivatives
D000975:Antioxidants; D016227:Benzoquinones; D012333:RNA, Messenger; D014451:Ubiquinone; C036619:idebenone