Effect of 1,6-dihydro-2[2-(2-methylpropoxy)anilino]-6-oxo-5-pyrimidineca rboxyli c acid on ethanol-induced microvascular injury in rats.
To disclose the cytoprotective mechanism of 1,6-dihydro-2[2-(2-methyoxypropoxy)anilino]-6-oxo-5-pyrimidinecarb oxylic acid (CAS 98772-05-5, MAR-99), the effect of this compound on the microvascular injury in gastric mucosa induced by 99.5% ethanol in rats was studied. In this experiment, it was found that the elevation of vascular permeability observed at the early state of ethanol-induced gastric mucosal injury was closely correlated with the combined action of histamine and slow reacting substance (leukotriene C4, LTC4). MAR-99 (0.3-10 mg/kg p.o.) prevented dose-dependently the increase in vascular permeability. Furthermore, MAR-99 (10 mg/kg p.o.) improved the decrease in the number of histamine containing cells and histamine content, and prevented the production of LTC4. These results suggest that MAR-99 exerts its anti-microvascular injury effect by regulating the release of histamine and the production of LTC4 in glandular stomach against ethanol, and this effect may contribute to the anti-lesion effect of this compound.
Ishizuka
Y
Y
Research Laboratories, Roussel Morishita Co., Ltd., Shiga, Japan.
Kamisaki
T
T
Okamoto
H
H
Kawashima
M
M
Sato
M
M
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D004195:Disease Models, Animal; D000431:Ethanol; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology; D006168:Guinea Pigs; D006636:Histamine Release / Q000187:drug effects; D017997:Leukotriene C4 / Q000378:metabolism; D008297:Male; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014148:Tranexamic Acid / Q000031:analogs & derivatives / Q000494:pharmacology
D000897:Anti-Ulcer Agents; D011743:Pyrimidines; D017997:Leukotriene C4; D000431:Ethanol; C000665:cetraxate; D014148:Tranexamic Acid; C087838:MAR 99