In vivo study | Fenspiride, an anti-inflammatory agent with low anti-cyclooxygenase activity, was administered orally to rats at a dose of 60-200 mg/kg, inhibits Endotoxin-induced but not Carrageenin-induced neutrophil migration into the peritoneal cavity and exudation into the peritoneal cavity. Treatment of rats with Fenspiride (200 mg/kg) inhibited the release of tumor necrosis factor by stimulating macrophages in a dose-dependent manner. Treatment of myringotomized rats with Fenspiride (topical application) inhibited the development of sclerosing lesions, while by intraperitoneal injection was ineffective. Treatment of endotoxemic guinea pigs with Fenspiride (60 mg/kg) significantly reduced serum levels (4.2 ng/mL vs. 2.3 ng/mL). And early rise of LPS-induced TNF concentrations in bronchoalveolar lavage fluid (55.7 ng/mL vs. 19.7 ng/mL). Fenspiride (60 mg/kg) also significantly reduced lipopolysaccharide-induced pulmonary Macrophage stimulation after N-formyl-methionyl-phenylalanine stimulation, compared with untreated control cells, enhanced release of arachidonic acid metabolites. Treatment of endotoxemic guinea pigs with Fenspiride (60 mg/kg) reduced elevated serum concentrations of extracellular type II phospholipase A2, the intensity of neutrophil infiltration into the alveoli, and the lethality of lipopolysaccharide. |