TXA2 (thromboxane A2) is known as a potent vasoconstrictive eicosanoid that can modulate pulmonary arterial pressure and hypoxic pulmonary vasoconstriction. TXA2 is involved in the early phases of oleic acid (OA)–induced lung injury, a representative model of ARDS/ALI (acute respiratory distress syndrome/acute lung injury)[3]. Ozagrel Hydrochloride is the hydrochloride form of Ozagrel. TXA2 synthase activity was selectively inhibited by Ozagrel and its IC50 for the rabbit platelet enzyme was found to be 11nM[4]. To evaluate efficacy, 80 mg/kg ozagrel was administered intravenously 30 min prior to OA injection. Administration of ozagrel prevented an increase in expression of MCP-1 and IL-8 mRNA in whole lungs 3 h after OA injection. There was a significant decrease in the MCP-1/β-actin and IL-8/β-actin ratios in the OA + ozagrel group compared with the OA + saline group. Moreover, Ozagrel significantly inhibited the increase in TXB2 levels in BALF 1.5 h after OA injection. These results indicated that ozagrel reduces pulmonary vascular hyper-permeability, the inflammation that is manifested by infiltration of macrophages and neutrophils, and the over-expression of MCP-1 and IL-8 mRNA in lungs induced by OA injection[3].
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