Gastroprotective effect of malotilate in indomethacin- and ethanol-induced gastric mucosal damage.

Malotilate as a synthetic substance shares comparable hepatoprotective properties with various flavonoids. The gastroprotective effect of some flavonoids prompted us to ascertain the similar effectiveness of malotilate. The possible gastroprotectivity was examined in gastric mucosal damage in rats induced by indomethacin (20 mg.kg-1) or ethanol (96%). Oral pretreatment with malotilate (25, 50, 100, 200 and 400 mg.kg-1) reduced the extent of lesions induced by both indomethacin and ethanol. Histological analyses also revealed a mitigating effect on the severity of gastric mucosal lesions. Similar results were obtained in the group of rats pretreated with 5 mg.kg-1 indomethacin followed by oral administration of 96% ethanol. This finding suggests that the effect of malotilate on rat gastric mucosa is independent of endogenous prostaglandin production.

Pentoxifylline-associated reduction of indomethacin-induced rat gastric mucosal injury is supported by decreased lipid peroxidation.

Pentoxifylline pretreatment protects rat gastric mucosa against indomethacin-induced damage. Lipid peroxidation after indomethacin treatment (determined as thiobarbituric acid reactants) was significantly reduced by a single dose of pentoxifylline. The same was true for pentoxifylline administration for 6 days. There is a relationship between reduced lipid peroxidation, decreased number of circulating activated neutrophils and diminished disposition for acute gastric mucosal lesions induced by indomethacin in pentoxifylline-pretreated rats.

[The role of polymorphonuclear leukocytes in the development of gastric lesions induced by indomethacin and ethanol and the relation of vascular permeability]. / Uloha polymorfonukleárnych leukocytov pri vzniku zalúdocných lézií vyvolaných indometacínom a etanolom vo vzt'ahu k cievnej permeabilite.

The relationship between a reduced number of polymorphonuclear leukocytes (PMN), activated PMN/NBT (+) PMN/, permeability of gastric vessels, and disposition for the development of gastric lesions was studied following administration of indomethacin or ethanol in rats. Decrease in the number of circulating neutrophils and in the number of NBT (+) PMN after 3- or 6-day administration of methotrexate was found to diminish the disposition for the development of gastric lesions. Six-day administration of pentoxifylline resulted in a decreased number of NBT (+) PMN and in a diminished disposition for gastric mucosa injury induced by indomethacin, yet failed to reduce the occurrence rate of lesions after ethanol administration. No direct relationship was established between changes in gastric vascular permeability and decreased disposition for the development of gastric lesions after administration of methotrexate or pentoxifylline. (Fig. 3, Ref. 30.)