Rebamipide reduces indomethacin-induced gastric injury in mice via down-regulation of ICAM-1 expression.
Non-steroidal anti-inflammatory drugs (NSAIDs) induced gastric mucosal injury occurs through subsequent events following free radical production derived from activated neutrophils. In this study, we hypothesized that rebamipide, a novel anti-ulcer agent, exerts a protective effect on NSAID-induced gastric injury through its antioxidant properties. The protective effect of rebamipide in a mouse model of indomethacin-induced gastric injury and mechanisms for this effect were investigated. Pre-treatment with rebamipide significantly inhibited indomethacin-induced gastric mucosal injury in mice. Gastric thiobarbituric acid reactive substances (TBARS) levels and myeloperoxidase (MPO) activity substantially increased 3 hr after indomethacin administration. These increases were significantly inhibited by pre-treatment with rebamipide. Furthermore, rebamipide pre-treatment notably decreased intercellular adhesion molecule-1 (ICAM-1) expression that was up-regulated in gastric tissue treated with indomethacin. Therefore, rebamipide may reduce indomethacin-induced gastric mucosal injuries through its antioxidant effect, which inhibits the neutrophil activation step following up-regulation of ICAM-1 expression on endothelial cells.
Hiratsuka
Tetsuro
T
Third Department of Internal Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan.
Futagami
Seiji
S
Shindo
Tomotaka
T
Hamamoto
Tatsuhiko
T
Ueki
Nobue
N
Suzuki
Kenji
K
Shinji
Yoko
Y
Kusunoki
Masanori
M
Shinoki
Kei
K
Wada
Ken
K
Miyake
Kazumasa
K
Gudis
Katya
K
Tsukui
Taku
T
Sakamoto
Choitsu
C
D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000502:physiology; D015536:Down-Regulation; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology*; D007213:Indomethacin / Q000009:adverse effects*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D051379:Mice; D008813:Mice, Inbred ICR; D018375:Neutrophil Activation; D015363:Quinolones / Q000494:pharmacology*; D015854:Up-Regulation
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D000975:Antioxidants; D015363:Quinolones; D018799:Intercellular Adhesion Molecule-1; C052785:rebamipide; D000409:Alanine; D007213:Indomethacin