Effects of a platelet-activating factor antagonist, CV-6209, on gastric mucosal lesions induced by ischemia-reperfusion.
Recent research was shown that oxygen-derived free radicals are involved in the pathogenesis of various diseases, including ischemia-reperfusion injury. We have also reported that oxygen-derived free radicals and lipid peroxidation may play an important role in gastric mucosal injury induced by ischemia-reperfusion. The hypoxanthine-xanthine oxidase system and neutrophils are considered important sources of oxygen-derived free radicals in this process. In recent years, it also has been shown that serum platelet-activating factor (PAF) levels increased during ischemia-reperfusion, and that induction of superoxide generation by neutrophils is one of the important biological effects of PAF. In the present study, we examined the effect of CV-6209, a specific PAF receptor antagonist, on gastric mucosal injury induced by ischemia-reperfusion, to shed some light on the possible involvement of PAF in such lesions. CV-6209 significantly attenuated the gastric mucosal injury induced by ischemia-reperfusion, and inhibited both an increase of thiobarbituric acid reactive substances and a decrease of alpha-tocopherol in gastric mucosa after ischemia-reperfusion. However, CV-6209 had no effect on gastric mucosal blood flow during ischemia-reperfusion. These results suggest that endogenous PAF may play an important role in gastric mucosal injury induced by ischemia-reperfusion, and that CV-6209 exerts its beneficial effect mainly by inhibiting neutrophil superoxide production induced by PAF.
Yoshikawa
T
T
First Department of Medicine, Kyoto Prefectural University of Medicine, Japan.
Takahashi
S
S
Naito
Y
Y
Ueda
S
S
Tanigawa
T
T
Yoshida
N
N
Kondo
M
M
D000818:Animals; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D011726:Pyridinium Compounds / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D015427:Reperfusion Injury / Q000209:etiology*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014810:Vitamin E / Q000032:analysis
D010972:Platelet Activating Factor; D011726:Pyridinium Compounds; D017392:Thiobarbituric Acid Reactive Substances; C053321:CV 6209; D014810:Vitamin E