Partial protective effect of Y-27632, a Rho kinase inhibitor, against hepatic ischemia-reperfusion injury in rats.
(+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl)-cyclohexanecarboxamide dihydrochloride (Y-27632), a Rho kinase inhibitor, has a suppressive effect on the functions of polymorphonuclear leukocytes. In this study, the influence of Y-27632 on ischemia-reperfusion injury of the liver was examined in rats. Y-27632 (3 mg/kg) or vehicle alone was intravenously injected into rats 60 min before occlusion. Blood samples were obtained for 48 h after reperfusion. At the end of the experiment, the hepatic content of myeloperoxidase, which reflects the number of polymorphonuclear leukocytes in liver tissues, was determined. The increases in serum hepatic aminotransferases and inflammatory cytokines [tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6] after reperfusion were partially, but significantly, inhibited by Y-27632. The increased hepatic myeloperoxidase content was significantly lowered by Y-27632. These results suggest that Y-27632 has a partial protective effect against hepatic ischemia-reperfusion injury through the suppression of polymorphonuclear leukocytes and inflammatory cytokines.
Kawaguchi
Atsuhiro
A
Department of Clinical Pharmacology, Jichi Medical School, Tochigi 329-0498, Japan.
Ohmori
Masami
M
Fujimura
Akio
A
D000410:Alanine Transaminase / Q000097:blood / Q000187:drug effects; D000577:Amides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D007275:Injections, Intravenous; D047908:Intracellular Signaling Peptides and Proteins; D008099:Liver / Q000098:blood supply / Q000601:surgery / Q000648:ultrastructure; D008107:Liver Diseases / Q000150:complications / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D017346:Protein Serine-Threonine Kinases / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D011725:Pyridines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy / Q000517:prevention & control*; D013997:Time Factors; D054460:rho-Associated Kinases
D000577:Amides; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D011725:Pyridines; C108830:Y 27632; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases