Disease relevance of thromboxane B2

• More frequent dazmegrel treatment (100 mg/kg p.o. every 8 h from Day 1 to killing) resulted in complete TXB2 synthetase inhibition, AA metabolism diversion, and increased tumor growth and metastasis [1].
• Ovarian anaplastic cancer and adenocarcinoma (n = 12) produced 6-keto-PGF1 alpha on average 11.6-fold (95% CI from 5.2 to 26.0) 6-keto-PGF1 alpha and TxB2 on average 30.0-fold (95% CI from 13.5 to 66.7) over production by healthy ovaries, and the ratio of 6-keto-PGF1 alpha to TxB2 shifted to the dominance of TxB2 [2].
• Similarly ovarian metastases of breast cancer, tubal cancer, and colon cancer produced increasingly 6-keto-PGF1 alpha (mean, 20.7 ng/mg protein/min) and TxB2 (5.1 ng/mg protein/min) [2].
• The effect of haemorrhagic hypotension on the levels of prostaglandin E2 (PGE2), thromboxane B2 (TXB2), and 6-keto prostaglandin F1 alpha (6-keto-PGF1 alpha) in cortical tissue of rats was studied [3].
• The development of subepithelial, glomerular immune-complex deposits and proteinuria was associated with a significant stimulation of glomerular PGE2 (87%) and TXB2 (183%) formation [4].

High impact information on thromboxane B2

• Plasma levels of beta-thromboglobulin (beta-TG) and of thromboxane B2 (TxB2), in vivo measures of platelet activity, were elevated three- and 10-fold [5].
• When PG biosynthesis was determined in NL tissue separately, low mean levels of PGE2 and PGF2 alpha (less than 2 pmol/mg protein/15 min), intermediate levels of PGD2 and 6-keto-PGF1 alpha (6KPGF1 alpha) (2-7 pmol/mg protein/15 min), and high levels of thromboxane B2 (TXB2) (greater than 7 pmol/mg protein/15 min) were observed [6].
• Synthesis of selected products (TXB2, PGD2, and PGE2) increased markedly over time (up to 10.6, 3.5, and 0.9 micrograms/g, respectively) [1].
• The overall metabolic profile was TXB2 much greater than PGD2 greater than PGF2 alpha greater than 6-keto-PGF1 alpha greater than PGE2 on Day 15 and TXB2 much greater than PGD2 much greater than PGF2 alpha greater than 6-keto-PGF1 alpha on Day 24 [1].
• C3b at concentrations ranging from 20 to 80 micrograms/ml induced synthesis of large quantities of the arachidonic acid cyclooxygenation products thromboxane B2 (TXB2) and prostaglandin E (PGE) but failed to trigger an oxidative burst [7].

Chemical compound and disease context of thromboxane B2

• Chronic treatment of M5-bearing mice with dazmegrel (UK-38,485), a selective thromboxane synthetase inhibitor (100 mg/kg p.o. daily, from Day 7 to killing), resulted in incomplete TXB2 synthesis inhibition, AA metabolism diversion toward the other prostaglandins, and no effects of tumor growth and metastasis [1].
• After ischemia and reperfusion in the control group, the levels of TxB2 and PGF2 alpha increased in both CN and HPC [8].
• We hypothesized that infusion of amr would cause pulmonary vasodilation and reduce serum TxB2 and TNF levels in piglets with late phase GBS-induced pulmonary hypertension [9].
• The 6-keto-PGF1a/TxB2 ratio in endometrial cancer (0.9; 0.3-1.5) was smaller (p less than 0.02) than that in healthy endometrium (3.3; 1.9-4.8) [10].
• RESULTS: Reperfusion following focal cerebral ischemia resulted in increases in TXB2 at 5 min and 6-keto-PGF1 alpha at 30 min and a decrease in the ratio of epoprostenol (PGI2)/thromboxane A2 (TXA2) (6-keto-PGF1 alpha/TXB2) at 5 min in hippocampus, striatum, and cerebral cortex [11].

Biological context of thromboxane B2

• The pharmacokinetics were evaluated by investigation of the time- and dose-dependent effects of ABT-761, and the pharmacologic selectivity of ABT-761 was evaluated based on calcium ionophore-stimulated leukotriene B4 (LTB4) and thromboxane B2 (TXB2) biosynthesis ex vivo in whole blood [12].
• The minimum serum TXB2 concentration, however, did not differ among the different genotypes (P=.32, ANOVA) [13].
• Moreover, the production of TXB2 during whole blood clotting was assessed as an index of the cyclooxygenase activity of platelet PGHS-1 ex vivo [14].
• 14C-Serotonin (5-hydroxytryptamine) release from preloaded platelets, and thromboxane B2 (TxB2) formation were evaluated simultaneously with platelet aggregation [15].
• The level of 6-keto-PGF1 alpha in amniotic fluid correlated with the pregnancy week in normal and preeclamptic pregnancies, and the levels of TxB2 in amniotic fluid in normal, preeclamptic, and rhesus-immunized pregnancies [16].

Anatomical context of thromboxane B2

• Purified eosinophils produced TXB2 predominantly after stimulation with PMA, fMLP, and PAF [17].
• Ciliary body--iris microsomes prepared 15 min after paracentesis synthesized increased amounts of all cyclo-oxygenase products assayed, most notably TXB2 and PGE2 [18].
• 6 KetoPGF1 alpha and TxB2 synthesis was also measured in incubates of blood vessels supplying and transplanted with the kidney in these animals [19].
• TXB2 synthesis was significantly greater in allotransplanted pancreas than isotransplanted pancreas from the 5th day after transplantation [20].
• During the phase of cellular rejection (3-5 days), TxB2 synthesis was selectively elevated in allografted renal cortex, renal artery, renal vein, and abdominal aorta in comparison with isografted tissues [19].

Associations of thromboxane B2 with other chemical compounds

• No differences were observed in NL and LC tissue for the major LC histological cell types when PGD2, TXB2, or 6KPGF1 alpha biosyntheses were compared [6].
• After discontinuation of nabumetone, urinary 11-dehydro-TXB2 excretion and whole blood TXB2 production returned to predrug levels with a similar timecourse that was consistent with the elimination half-life of its active metabolite [14].
• Unilaterally pregnant rats were killed on Days 20 and 21 of pregnancy (delivery = Day 21.5) and uterine tissue was removed and analyzed for prostaglandin (PG) E, PGF, thromboxane B2 (TxB2), and 6-keto-PGF1 alpha (6KF) by radioimmunoassay [21].
• Similarly, incubation with aspirin (10 microM) did not affect contractile responses to endothelin-1, but significantly reduced TxA2 production in coronary artery segments as judged by a decrease in thromboxane B2 (TxB2) from 4.77 +/- 0.98 to 1.38 +/- 0.36 ng g-1 2 h-1 [22].
• This study assessed the effect of pulsatile blood flow on plasma thromboxane and prostacyclin profiles during cardiopulmonary bypass by serial measurement of their stable metabolites, thromboxane B2 (TxB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) [23].

Gene context of thromboxane B2

• The daily administration of low-dose aspirin (40 mg), a selective inhibitor of platelet PGHS-1, caused a cumulative inhibition of urinary 11-dehydro-TXB2 and whole blood TXB2 production that recovered with a timecourse consistent with platelet turnover [14].
• Effects of misoprostol, a synthetic prostaglandin E1 (PGE1) analogue, on cyclooxygenase-2 (COX-2) protein level and exudate prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) level were investigated in acute carrageenan-induced air pouch inflammation in rats [24].
• To determine whether the induction of immune-mediated glomerular injury influences the formation of cyclooxygenase products by glomerular cells, we determined prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) (as the stable metabolite of TXA2) formation in isolated glomeruli of rats with passive Heymann nephritis (PHN) [4].
• Regression analysis revealed significant correlations between GA, TxB, PGI, and arterial oxygenation [25].
• In vitro, nicotine (2 X 10(-3) mol/liter) inhibited pulmonary TxB2 production by 70% and simultaneously stimulated the production of 6-keto-prostaglandin F1 alpha, a stable metabolite of PGI2, by 40%, which suggest that nicotine does not exert its effect at the cyclooxygenase level [26].

Analytical, diagnostic and therapeutic context of thromboxane B2

• The in vitro glomerular TxB2 synthesis correlated inversely with the presacrifice GFR and filtration fraction [27].
• Ex vivo production of thromboxane B2 (TXB2) and 6-keto PGF1 alpha was determined by specific radioimmunoassay in serum from venous blood incubated for 1 hr (37 degrees) [28].
• In the transplanted aorta, TXB2 was significantly greater in the allograft group from the third posttransplant day [20].
• The plasma concentrations of thromboxane B2 (TXB2, the stable breakdown product of TXA2) were also measured by ELISA to assess whether transdermal nicotine acutely affects TXA2 production [29].
• This was in contrast to the control group were TXB2 levels further increased up to a mean of 718+/-333 pg/ml at the end of CPB (P=0.016) [30].

References