Effects of diacerein on indomethacin-induced gastric ulceration.
We investigated the effect of diacerein, an antiosteoarthritic agent, and its metabolite, rhein, on the production of reactive oxygen species (ROS) from neutrophils as well as the protective effect of diacerein on indomethacin-induced gastric ulceration and its protection mechanism. Rhein inhibited the ROS production from N-formyl-methionyl-leucyl-phenylalanine or phorbol-12-myristate-13-acetate-activated human peripheral neutrophils. Indomethacin-induced gastric ulceration was significantly inhibited by oxygen radical scavengers and 16,16-dimethyl-prostaglandin E(2) (dmPGE(2)) but not by allopurinol. Diacerein inhibited indomethacin-induced gastric ulceration in a dose-dependent manner. Diacerein did not affect the gastric mucosal PGE(2) content. In addition, diacerein inhibited HCl + ethanol-induced gastric ulceration. These data indicate that the inhibitory effect of diacerein on indomethacin-induced gastric ulceration could be mediated not by the augmentation of gastric mucosal PGE(2) production but by the suppression of ROS production based on its inhibition of neutrophil activation.
Tamura
T
T
Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Shizuoka, Japan. tadafuni.tamura@kyowa.co.jp
Yokoyama
T
T
Ohmori
K
K
D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D000431:Ethanol; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D006851:Hydrochloric Acid; D007213:Indomethacin; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy*
D000880:Anthraquinones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D017382:Reactive Oxygen Species; D000431:Ethanol; C025292:diacerein; D015232:Dinoprostone; D006851:Hydrochloric Acid; D007213:Indomethacin; C020491:rhein