Plaunotol prevents indomethacin-induced gastric mucosal injury in rats by inhibiting neutrophil activation

Background: Activated neutrophils play a critical role in indomethacin-indu ced gastric mucosal injury. Aim: To investigate the effect of plaunotol, an anti-ulcer agent, on neutro phil activation in vitro and its effect on gastric mucosal injury and gastr ic 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 neutrop hil elastase release, production of O-2(-), intracellular calcium concentra tion and expression of adhesion molecules CD11b and CD18 in activated neutr ophils in vitro. The effect of plaunotol on TNF-alpha production by monocyt es stimulated with endotoxin also was investigated in vitro. The effect of plaunotol (100 mg/kg, p.o.) on gastric mucosal injury and neutrophil accumu lation was investigated in male Wistar rats given indomethacin (30 mg/kg, p .o.). Results: Plaunotol inhibited the fMLP-induced release of neutrophil elastas e from activated neutrophils, as well as the opsonized zymosan-induced prod uction of O-2(-) by neutrophils. Plaunotol significantly inhibited increase d levels of intracellular calcium, a second messenger of neutrophil activat ion, in vitro. The fMLP-induced increases in CD11b and CD18 expression were also inhibited by plaunotol in vitro. Plaunotol inhibited monocytic produc tion 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.