Troxipide, a novel antiulcer compound, has inhibitory effects on human neutrophil migration and activation induced by various stimulants

Background. Neutrophils are considered to be involved in the pathogenesis o f Helicobacter pylori-associated gastroduodenal diseases on account of thei r potent biological functions as effector cells. Troxipide, a new antiulcer compound used for patients with gastric ulcer or gastritis, has been shown to inhibit migration and activation of guinea pig neutrophils, but little is known about the pharmacological effects on human neutrophils. Aims. To study the effects of troxipide on chemotactic migration and supero xide generation by human neutrophils. Methods. The chemotactic response of neutrophils was determined in a multi- well chamber with a polycarbonate filter and the generation of O-2- by neut rophils was measured using a chemiluminescence method. Concentrations of tr oxipide in gastric mucosa were measured by high-performance liquid chromato graphy Results, incubation of neutrophils with 10(-6) to 10(-4) M troxipide caused inhibition of recombinant interleukin-8-induced migration. These concentra tions of troxipide also inhibited superoxide generation by neutrophils stim ulated by formyl-methionyl-leucyl-phenylalanine or platelet activating fact or. These phenomena were not simply due to the direct cytotoxic effects sin ce the above concentrations of troxipide did not induce neutrophil apoptosi s. The concentrations of troxipide detected in the gastric mucosa after ora l administration were in the range able to inhibit chemotactic migration an d superoxide generation by neutrophils in vitro. Conclusion. These results suggest that troxipide may exert its therapeutic effect in patients with gastric ulcer or gastritis by inhibiting inflammato ry responses and mucosal injury mediated by neutrophils in gastric mucosa.