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Plaunotol prevents indomethacin‐induced gastric mucosal injury in rats by inhibiting neutrophil activation
Author(s) -
Kazunori Murakami,
Kenji Okajima,
Naoaki Harada,
Hirotaka Isobe,
Liu W,
Masayoshi Johno,
Hiroaki Okabe
Publication year - 1999
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1046/j.1365-2036.1999.00481.x
Subject(s) - medicine , neutrophile , pharmacology , inflammation , immunology
Background: Activated neutrophils play a critical role in indomethacin‐induced gastric mucosal injury. Aim: To investigate the effect of plaunotol, an anti‐ulcer agent, on neutrophil activation in vitro and its effect on gastric mucosal injury and gastric accumulation of neutrophils in rats given indomethacin. Methods: Human monocytes and neutrophils were isolated from the peripheral blood of healthy volunteers. We examined the effect of plaunotol on neutrophil elastase release, production of O 2 − , intracellular calcium concentration and expression of adhesion molecules CD11b and CD18 in activated neutrophils in vitro . The effect of plaunotol on TNF‐α production by monocytes stimulated with endotoxin also was investigated in vitro . The effect of plaunotol (100 mg/kg, p.o.) on gastric mucosal injury and neutrophil accumulation was investigated in male Wistar rats given indomethacin (30 mg/kg, p.o.). Results: Plaunotol inhibited the fMLP‐induced release of neutrophil elastase from activated neutrophils, as well as the opsonized zymosan‐induced production of O 2 − by neutrophils. Plaunotol significantly inhibited increased levels of intracellular calcium, a second messenger of neutrophil activation, in vitro . The fMLP‐induced increases in CD11b and CD18 expression were also inhibited by plaunotol in vitro . Plaunotol inhibited monocytic production of TNF‐α, a potent activator of neutrophils. Both gastric mucosal injury and gastric neutrophil infiltration in rats given indomethacin were significantly inhibited by the oral administration of plaunotol. Conclusions: Plaunotol inhibits indomethacin‐induced gastric mucosal injury, at least in part by inhibiting neutrophil activation.