FLAVONOID-INDUCED GASTROPROTECTION IN RATS - ROLE OF BLOOD-FLOW AND LEUKOCYTE ADHERENCE

To elucidate the mechanisms of flavonoid-induced protection against no nsteroidal anti-inflammatory drug (indomethacin)-induced acute gastric damage, the effects of 5-methoxyflavone and 5-methoxyflavanone on the gastric vasculature were compared both in vivo (using laser Doppler f lowmetry in anaesthetized rats) and in vitro on rat superior mesenteri c arteries. The effects of the compounds on indomethacin-induced leuko cyte adherence to mesenteric venules were investigated by intravital v ideomicroscopy. Oral 5-methoxyflavone reduced indomethacin-induced mac roscopic damage by 38 to 99% (ED50 = 5.5 mg/kg). Damage was not signif icantly reduced by 5-methoxyflavanone. Light microscopy studies also d emonstrated a reduction in damage severity, 5-Methoxyflavone, but not 5-methoxyflavanone, increased the gastric conductance significantly. T he effects on isolated mesenteric arteries correlated with the effects on in vivo conductance. Finally, indomethacin-induced leukocyte adher ence was inhibited to a greater extent by 5-methoxyflavone than by 5-m ethoxyflavanone, In conclusion, the flavonoid 5-methoxyflavone provide s gastroprotection against nonsteroidal anti-inflammatory drug-induced gastric damage, A structurally similar compound, 5-methoxyflavanone, demonstrated minimal gastroprotective activity, suggesting that the do uble bond of 5-methoxyflavone is required for biological activity, The finding that 5-methoxyflavone (but not 5-methoxyflavanone) significan tly increased gastric vascular perfusion and reduced leukocyte adheren ce to mesenteric venules suggests that these mechanisms may contribute to the flavonoid's gastroprotective activity.