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]. 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].
Ozagrel/奥扎格雷 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Rabbit pulmonary artery endothelial cells
10 µM
40 min
Inhibited TXA2 synthase, reduced TXB2 release, and attenuated stretch-induced contraction
Br J Pharmacol. 1997 Sep;122(2):199-208.
HEK293 cells
10 µM
20 seconds
To investigate the effect of Ozagrel on 12-HHT and TxB2 production. Results showed that Ozagrel partially inhibited 12-HHT production but completely inhibited TxB2 production.
J Lipid Res. 2013 Nov;54(11):2979-87.
Ozagrel/奥扎格雷 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Guinea-pigs
Capsaicin-induced cough model
Oral
10, 30, and 100 mg/kg
Administered 1 hour before capsaicin provocation
To evaluate the inhibitory effect of Ozagrel on capsaicin-induced cough, results showed Ozagrel dose-dependently reduced cough counts (ED50 value, 26.3 mg/kg).
Br J Pharmacol. 2000 Sep;131(2):266-70
Mongolian gerbils
Transient bilateral carotid artery occlusion model
Intraperitoneal injection
30 mg/kg
Single dose
To evaluate the neuroprotective effects of Ozagrel against ischemia-induced neuronal loss. Results showed that Ozagrel did not significantly protect CA1 neurons in the hippocampus from ischemia-induced loss.
Br J Pharmacol. 1996 Aug;118(7):1592-6
Sprague Dawley rats
Cortical spreading depression (CSD) model
Topical epidural administration
1 mM
Single dose, observed for 50 minutes
To evaluate the effect of Ozagrel on CSD-evoked cerebral oligemia. Results showed that Ozagrel partially inhibited the early decrease in CBF ("dip" phase) but had no significant effect on the later persistent oligemia.
To evaluate the effect of antiplatelet therapy in a mouse model of adenomyosis. Results showed that Ozagrel dose-dependently suppressed myometrial infiltration, improved generalized hyperalgesia, reduced uterine contractility, and lowered plasma corticosterone levels, improved the expression of some proteins known to be involved in adenomyosis and slowed down the process of fibrogenesis.
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