Antiapoptotic and protective effects of roscovitine on ischemia-reperfusion injury of the rat liver.
OBJECTIVE
This study was designed to investigate the role of apoptosis on liver IR injury and to determine the effects of roscovitine on this process.


METHODS
Rat livers pretreated with roscovitine received 60 min right lobe ischemia followed by 4 h (n=8) and 24 h (n=8) reperfusion. Tissue injury was evaluated by serum alanine aminotransferase, aspartate aminotransferase, tissue malondialdehyde, myeloperoxidase measurements and histological examination. Dead (apoptotic and necrotic) hepatocytes were determined by trypan blue dye and apoptosis was evaluated with M30 monoclonal antibody.


RESULTS
Administration of roscovitine significantly decreased both apoptotic and dead hepatocyte counts compared to controls (P<0.01). Liver transaminase levels were decreased significantly in the roscovitine-pretreated groups (P<0.05). In the groups evaluated 24 h after reperfusion, MPO levels (P<0.02) and leukocyte infiltration on histologic sections were decreased significantly in the roscovitine-administered group compared to its control.


CONCLUSIONS
This study indicates that hepatocyte apoptosis may play a role in the development of IR injury of the liver. Administration of roscovitine may be beneficial in preventing this injury.
Topaloglu
Serdar
S
Department of Surgery, Hacettepe University School of Medicine, Ankara, Turkey.
Abbasoglu
Osman
O
Ayhan
Ayse
A
Sokmensuer
Cenk
C
Kilinc
Kamer
K
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001219:Aspartate Aminotransferases / Q000097:blood; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000293:injuries / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011687:Purines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D000077546:Roscovitine
D004791:Enzyme Inhibitors; D011687:Purines; D000077546:Roscovitine; D008315:Malondialdehyde; D009195:Peroxidase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase