Disease relevance of ozagrel

• Effects of OKY 046, a thromboxane-synthase inhibitor, on renal function in nonazotemic cirrhotic patients with ascites [1].
• However, insulin clearance was not significantly affected by OKY-046, implying that inhibition of Tx synthetase reduced proteinuria independently of changes in renal hemodynamics [2].
• Pretreatment with a lower molecular weight imidazole derivative OKY 046 (N = 9) inhibited all Tx synthesis after ischemia [3].
• Histologically, the liver preserved for 6 hr in simple cold lactated Ringer's solution exhibited interstitial edema, various degrees of hepatocyte swelling, and sinusoidal stenosis, as well as dilatation, while the livers treated with OKY-046 demonstrated much less hepatocyte swelling, and change in sinusoidal width was nearly absent [4].
• The triphasic relationship between ipsilateral renal blood flow and ureteral pressure previously found following unilateral ureteral obstruction was observed despite OKY-046 infusion [5].

High impact information on ozagrel

• Pretreatment with the Tx synthetase inhibitor OKY 046 (n = 7) lowered baseline plasma and lymph TxB2 levels to 22 and 52 pg/ml (P less than 0.05) and prevented the IL-2-induced increase in plasma and lung lymph TxB2 (P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)[6]
• We, therefore, evaluated the effects of a thromboxane A2 receptor antagonist SQ-29,548 compared to those of a thromboxane A2 synthetase inhibitor OKY-046 on osteogenic sarcoma-induced platelet aggregation and thromboxane A2 release [7].
• In both cell lines, the rate of synthesis of TXA2 was very low and the selective blockade of its synthesis (by two other TXA2 synthase inhibitors, OKY-046 and Ridogrel) or action (by the TXA2 receptor antagonist BM-13,177) did not alter matrix production or TGF-beta mRNA levels [8].
• Pretreatment with OKY-046 led to reduced TxB2 levels of 149 +/- 17 pg/mL, normal lung histology, and 83 +/- 13 PMN/20 HPF, a value similar to that of the sham group and lower than that of the placebo-treated group (p less than 0.05) [9].
• Prior to tourniquet inflation, both OKY 046 and ketoconazole lowered plasma TxB2 levels as well as the L/P ratio (p less than 0.05) [3].

Chemical compound and disease context of ozagrel

• The effect of the thromboxane A2 synthesis inhibitor OKY-046 on renal function in rabbits following release of unilateral ureteral obstruction [10].
• In patients with chronic bronchitis, the cough threshold was significantly greater with indomethacin (5.94 (GSEM 1.50) microM) than with placebo (3.41 (GSEM 1.33) microM and OKY-046 2.97 (GSEM 1.43) microM) [11].
• The reduction in thromboxane A2 production associated with increased prostacyclin appeared to be the major mechanism of the interruption of the thrombus formation by OKY-046 [12].
• In contrast, both inhibition of Tx synthesis (Tx < 3 ng/ml) with OKY-046 and blockade of the Tx receptor with SQ-30741 (Tx > 20 ng/ml) were not only associated with significantly lower peak PVRs (<0.2 cmH2O x ml(-1) x min) but also with attenuated increase in lung wet-to-dry ratio and airway edema [13].
• Pretreatment with OKY-046 (100 mg/kg i.v., n = 8) prevented PMA-induced increases in TxB2, LTB4, and pulmonary edema formation but did not prevent the increase in PVR.(ABSTRACT TRUNCATED AT 250 WORDS)[14]

Biological context of ozagrel

• Administration of OKY 046 decreased systolic and mean arterial blood pressure and urinary excretion of thromboxane and protein in spontaneously hypertensive rats [15].
• OKY 046 (10(-5) M), a thromboxane synthase inhibitor, significantly tempered the rapid vascular smooth muscle cell growth in SHR by 9% for doubling time and by 10% for [3H]thymidine uptake [16].
• The geometric mean value of PC20 FEV1 increased significantly from 0.55 to 2.24 mg/ml after oral OKY-046, but was unchanged after inhalation of OKY-046 and after oral administration of AA-861 [17].
• Baseline values of FEV1 and forced vital capacity (FVC) were not altered by oral OKY-046, oral AA-861, or inhaled OKY-046 [17].
• Infusion of OKY-046 significantly inhibited pulmonary thromboxane B2 delivery, attenuated the early increase in pulmonary vascular resistance, and blocked the increase in systemic vascular resistance [18].

Anatomical context of ozagrel

• Maximal degranulation of atypical mast cells was delayed to 6 hours with OKY-046, whereas these cells responded completely at 1 hour without OKY-046 [19].
• We conclude that OKY-046 reduces post-preservation reoxygenation injury by protecting sinusoidal endothelial cells and hepatocytes [4].
• The frequency of antidonor precursor cytotoxic T cells (pCTL), as measured by limiting dilution assay, was consistently lower in allografts from OKY-046-treated animals (1/3146-1/5160) compared with vehicle treatment (1/661-1/1878), while no difference in pCTL ranges were seen in splenocytes from both groups [20].
• Tracheas were also pretreated with meclofenamate (10(-6) M) (a cyclooxygenase inhibitor) and UK 37,248 (10(-8) to 10(-5) M) and OKY 046 (10(-9) to 10(-6) M) (thromboxane synthetase inhibitors), and the thiamylal protocol was repeated [21].
• These changes were completely blocked in the OKY-046 group, except for the neutrophil depletion and the increase in lung lymphatic flow [22].

Associations of ozagrel with other chemical compounds

• We conclude that OKY-046 alters the antigen-induced response of atypical mast cells, the subsequent cellular and clinical late-phase response, and prevents the increase in histamine response [19].
• Platelet aggregation and thromboxane B2 (TXB2) formation induced by collagen and arachidonic acid were suppressed by the infusion of OKY-046, while both were not affected by the infusion of vehicle [23].
• Bradykinin instilled by the airway route significantly decreased systemic blood pressure but this effect was not altered in animals pretreated with either indomethacin or OKY-046 [24].
• CONCLUSIONS: We have demonstrated that atherosclerosis in aortic allografts is inhibited by the continuous administration of either OP-2507 or OKY-046, and a combination of both agents strongly increases this inhibitory effect [25].
• Immunoglobulin E-mediated bronchoconstriction in actively sensitized rats was also inhibited by both DP-1904 (1, 10 mg/kg) and OKY-046 (100 mg/kg) [26].

Gene context of ozagrel

• In the next series of experiments, ET-1 and ET-3 were administered after administration of 20 mg/kg of OKY-046 [27].
• OKY-046 showed no effects in animals treated with ET-1, as in those pre-treated with INDO, while it significantly inhibited the decreases in hepatic blood flow induced by ET-3 [27].
• Indomethacin and OKY-046 did not, however, reduce 125I-EGF binding [28].
• The administration of OKY-046 (inhibitor of TXA2 synthesis) to the University of Wisconsin solution suppressed this reduction in TXA2R number [29].
• OKY-046 also increased PCNA expression in the cortex and outer stripe in Sham-Nx animals [30].

Analytical, diagnostic and therapeutic context of ozagrel

• Reduced protein excretion (0.88 +/- 0.12 mg/min/g, n = 6, P less than 0.001) also occurred with inhibition of Tx synthetase by OKY-046, 10(-4) M, a dose that was shown in separate perfusions to inhibit urinary TxB2 excretion by greater than 85% [2].
• The addition of OKY-046 to the preservation solution, however, prevented the rise in reperfusion pressure almost completely and the increase in effluent enzyme levels [29].
• Despite the beneficial effects on allograft function, OKY-046 neither altered the morphologic appearance of the cellular infiltrate nor the systemic proliferative and cytotoxic anti-donor cellular immune responses [31].
• Six days following transplantation, renal TXB2 production was only partially inhibited in animals given continuous infusions of OKY-046, and remained markedly elevated [31].
• Chronic oral administration of OKY-046 ameliorated not only the renal hyperperfusion but increased urinary albumin excretion (UAE) at two weeks, but also the renal hypoperfusion, filtration fraction and UAE at 24 weeks [32].

References