Protective effect of platelet-activating factor antagonist on ischemia-induced liver injury in rats.
Platelet-activating factor (PAF), one of the chemical mediators related to inflammation reaction, is also involved in the pathologic state induced by endotoxin or ischemia. PAF antagonist has been reported to block the action of PAF and protect cells from its deleterious effects. The effects of a PAF antagonist, CV-6209, were evaluated in this study by means of a partial liver ischemia model, in which ischemia was induced by clamping only part of the liver without causing intestinal congestion. This model allowed the study of ischemic liver injury without influence from other organs. After 30, 60, and 90 minutes of ischemia, the bile flow, ATP level, and energy charge of the ischemic lobes were compared for the effects with and without CV-6209. After 60 minutes of ischemia, those that had received CV-6209 showed more bile production and higher ATP level and energy charge, with values of 0.25 +/- 0.05 ml/hr, 3.9 +/- 0.9 nmol/mg dry liver weight, and 0.61 +/- 0.02, respectively. In contrast, the values for the control group were 0.05 +/- 0.05 ml/hr, 1.7 +/- 0.8 nmol/mg dry liver weight, and 0.43 +/- 0.08, respectively. Other liver function tests (aspartate aminotransferase and lactate dehydrogenase levels) could also be improved if an appropriate dose of PAF antagonist were administered. The results imply that PAF, as has been suggested in other studies on ischemic injury, plays a role in liver ischemia and that its deleterious effects can be blocked by PAF antagonist. We conclude that the PAF antagonist offers promise in the field of liver surgery, including liver transplantation, as a means of protecting the liver from ischemic injury.
Wang
K S
KS
Department of Surgery II, Osaka University Medical School, Japan.
Monden
M
M
Kanai
T
T
Gotoh
M
M
Umeshita
K
K
Ukei
T
T
Mori
T
T
D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001646:Bile / Q000502:physiology; D001653:Bile Ducts, Intrahepatic / Q000187:drug effects / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D007511:Ischemia / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000098:blood supply* / Q000737:chemistry; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D011726:Pyridinium Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
D010972:Platelet Activating Factor; D011726:Pyridinium Compounds; C053321:CV 6209; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases