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 of Helicobacter pylori-associated gastroduodenal diseases on account of their 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.


OBJECTIVE
To study the effects of troxipide on chemotactic migration and superoxide 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 O2- by neutrophils was measured using a chemiluminescence method. Concentrations of troxipide in gastric mucosa were measured by high-performance liquid chromatography.


RESULTS
Incubation of neutrophils with 10(-6) to 10(4) M troxipide caused inhibition of recombinant interleukin-8-induced migration. These concentrations of troxipide also inhibited superoxide generation by neutrophils stimulated by formyl-methionyl-leucyl-phenylalanine or platelet activating factor. These phenomena were not simply due to the direct cytotoxic effects since the above concentrations of troxipide did not induce neutrophil apoptosis. The concentrations of troxipide detected in the gastric mucosa after oral administration were in the range able to inhibit chemotactic migration and superoxide generation by neutrophils in vitro.


CONCLUSIONS
These results suggest that troxipide may exert its therapeutic effect in patients with gastric ulcer or gastritis by inhibiting inflammatory responses and mucosal injury mediated by neutrophils in gastric mucosa.
Kusugami
K
K
First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Ina
K
K
Hosokawa
T
T
Kobayashi
F
F
Kusajima
H
H
Momo
K
K
Nishio
Y
Y
D000328:Adult; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002465:Cell Movement / Q000187:drug effects*; D002633:Chemotaxis / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D016481:Helicobacter Infections / Q000276:immunology / Q000503:physiopathology*; D006801:Humans; D007249:Inflammation; D007413:Intestinal Mucosa; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010880:Piperidines / Q000494:pharmacology*; D013276:Stomach Ulcer / Q000276:immunology / Q000503:physiopathology; D013481:Superoxides
D000897:Anti-Ulcer Agents; D010880:Piperidines; D013481:Superoxides; C028936:troxipide