Cyclosporin A pretreatment in a rat model of warm ischaemia/reperfusion injury.
OBJECTIVE
These studies investigated the role of apoptosis following ischaemia/reperfusion (I/R) injury to the liver and the effect of pretreatment with Cyclosporin A.


METHODS
Male Sprague-Dawley rats received 30 min of warm ischaemia followed by a period of reperfusion of 6 h. Rats were given olive oil or Cyclosporin A (30 mg/kg p.o.) the day before surgery. Neutrophil numbers were assessed in haematoxylin-eosin-stained sections of liver. In situ staining of sections using TdT-mediated dUTP-fluorescein nick-end labelling was carried out to determine the extent of apoptosis, followed by electron microscopy. Semi-quantitative polymerase chain reaction (PCR) analysis of the transcript for Fas antigen was performed.


CONCLUSIONS
High levels of apoptosis were observed in I/R injury, which were greatly ameliorated in Cyclosporin A-pretreated groups. PCR analysis indicated a reduction in the level of expression of Fas transcript in Cyclosporin A-treated rats. Histological analysis showed a significant increase in the number of neutrophils infiltrating I/R-injured tissue (62 +/- 10.69, n=16), which was markedly reduced by Cyclosporin A pretreatment (16 +/- 7, n=6, P<0.05). These results indicate a role of parenchymal apoptosis in the pathogenesis of I/R injury, which occurs in association with neutrophil infiltration, both of which can be significantly reduced by Cyclosporin A pretreatment.
Saxton
Nina E
NE
Transplant Biology, Queensland Institute of Medical Research, Royal Brisbane Hospital Post Office,. Brisbane, Qld 4029, Australia. ninas@qimr.edu.au
Barclay
Johanna L
JL
Clouston
Andrew D
AD
Fawcett
Jonathan
J
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology*; D004195:Disease Models, Animal; D006358:Hot Temperature; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D008099:Liver / Q000276:immunology / Q000473:pathology* / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D009504:Neutrophils / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology
D007166:Immunosuppressive Agents; D016572:Cyclosporine