Effect of pretreatment with FTY720 and cyclosporin on ischaemia-reperfusion injury of the liver in rats.
The effect of pretreatment with FTY720 (2-amino-2-[2-(4-octylphenyl)ethyl]-1,3-propanediol hydrochloride) or cyclosporin, or both, on neutrophil-mediated injury has been examined by use of a rat model of transient clamping of hepatic flow. Pretreatment with FTY720 alone or with cyclosporin induced a marked reduction of circulatory lymphocytes, whereas the use of these drugs in combination was very effective at suppressing the elevation of the number of peripheral polymorphonuclear neutrophils (PMN) after reperfusion. Pretreatment with cyclosporin, with or without FTY720, significantly reduced hepatic damage, whereas FTY720 alone tended to prolong hepatic damage. Pretreatment of cyclosporin alone, but not in combination with FTY720, significantly reduced the accumulation of PMN and led to lower myeloperoxidase levels in the damaged liver. In conclusion, pretreatment with cyclosporin, with or without FTY720, reduced hepatic damage after warm ischaemia-reperfusion, whereas pretreatment with FTY720 alone tended to prolong this damage.
Mizuta
K
K
Department of Clinical Pharmacology, Centre for Molecular Medicine, Jichi Medical School, Kawachi-gun, Tochigi, Japan.
Ohmori
M
M
Miyashita
F
F
Kitoh
Y
Y
Fujimura
A
A
Mori
M
M
Kanno
T
T
Hashizume
K
K
Kobayashi
E
E
D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology*; D000068876:Fingolimod Hydrochloride; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007958:Leukocyte Count / Q000187:drug effects; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D008297:Male; D018375:Neutrophil Activation / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D011409:Propylene Glycols / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000201:enzymology / Q000276:immunology*; D013110:Sphingosine / Q000031:analogs & derivatives; D000637:Transaminases / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D014409:Tumor Necrosis Factor-alpha; D016572:Cyclosporine; D009195:Peroxidase; D000637:Transaminases; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine