Complement plays an important role in gastric mucosal damage induced by ischemia-reperfusion in rats.
Ischemia-reperfusion (I/R) of stomach causes gastric mucosal injury. Complement can also cause tissue damage, however its role in gastric I/R injury has not been thoroughly investigated. We evaluated the effect of complement suppression in reducing damage to the gastric epithelium caused by local I/R. Local gastric ischemia was induced by clamping the left gastric artery. The blood-to-lumen clearance of 51Cr-labeled EDTA (51Cr-EDTA) served as an index of epithelial damage. 51Cr-EDTA clearance increased shortly after reperfusion with peak values at 10 min. Intraperitoneal administration of cobra venom factor (CVF; 50 units) prior to I/R, which reduced the serum complement value (CH50) to an undetectable level, remarkably suppressed the 51Cr-EDTA clearance following reperfusion. A monocarboxylic acid derivative of K-76 (K-76 COOH) reduced the CH50 by more than 30% (100 mg/kg) and 60% (200 mg/kg). Rats pretreated with K-76 significantly attenuated the increase in 51Cr-EDTA clearance produced by I/R. These results suggest that complement inhibitor could be used to protect gastric mucosal injury induced by local I/R stress.
Joh
T
T
First Department of Internal Medicine, Nagoya City University School of Medicine, Nagoya, Japan. tjoh@med.nagoya-cu.ac.jp
Ikai
M
M
Oshima
T
T
Kurokawa
T
T
Seno
K
K
Yokoyama
Y
Y
Okada
N
N
Itoh
M
M
D000818:Animals; D002860:Chromium Radioisotopes; D003169:Complement Inactivator Proteins / Q000494:pharmacology; D003165:Complement System Proteins / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004492:Edetic Acid / Q000378:metabolism; D004546:Elapid Venoms / Q000008:administration & dosage / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D005753:Gastric Mucosa / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D012717:Sesquiterpenes / Q000494:pharmacology
D002860:Chromium Radioisotopes; D003169:Complement Inactivator Proteins; D004546:Elapid Venoms; D012717:Sesquiterpenes; C038797:K 76 carboxylic acid; D003165:Complement System Proteins; D004492:Edetic Acid