Plaunotol prevents indomethacin-induced gastric mucosal injury in rats by inhibiting neutrophil activation.
BACKGROUND
Activated neutrophils play a critical role in indomethacin-induced gastric mucosal injury.


OBJECTIVE
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 O2-, intracellular calcium concentration and expression of adhesion molecules CD11b and CD18 in activated neutrophils in vitro. The effect of plaunotol on TNF-alpha 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 O2- 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-alpha, 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.
Murakami
K
K
Department of Laboratory Medicine, Kumamoto University School of Medicine, Honjo 1-1-1 Kumamoto 860-8556, Japan.
Okajima
K
K
Harada
N
N
Isobe
H
H
Liu
W
W
Johno
M
M
Okabe
H
H
D000818:Animals; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D002118:Calcium / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D004224:Diterpenes; D005233:Fatty Alcohols / Q000627:therapeutic use*; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D007213:Indomethacin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D018375:Neutrophil Activation; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013272:Stomach Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000897:Anti-Ulcer Agents; D015815:Cell Adhesion Molecules; D004224:Diterpenes; D005233:Fatty Alcohols; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C047686:plaunotol; D002118:Calcium; D007213:Indomethacin