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Results: 5

1.
Fig. 3.

Fig. 3. From: Metabolic profiling of murine plasma reveals an unexpected biomarker in rofecoxib-mediated cardiovascular events.

Accumulation of 20-HETE following treatment of murine hepatic S-9 fraction with rofecoxib, SC-560, and indomethacin. (A) Significant increase was observed in the production of 20-HETE in a time-related manner following the incubation of normal murine hepatic S-9 fraction and ARA with rofecoxib (1 μM; n = 6). (B) Significant increase was observed in the production of 20-HETE following a 3-h incubation of normal murine liver S-9 fraction and ARA with rofecoxib, SC-560, and indomethacin (1 μM each; n = 6), whereas a slight increase was observed with rofecoxib (100 nM; n = 6). Data represent the mean ± SD. Statistical significance was determined by a two-sided unpaired t test and one-way ANOVA (*P < 0.05).

Jun-Yan Liu, et al. Proc Natl Acad Sci U S A. 2010 September 28;107(39):17017-17022.
2.
Fig. 5.

Fig. 5. From: Metabolic profiling of murine plasma reveals an unexpected biomarker in rofecoxib-mediated cardiovascular events.

20-HETE but not rofecoxib accelerates ADP-induced rat platelet aggregation in vitro. (A) Aggregation percentage under a different concentration of rofecoxib or 20-HETE at 1 min after ADP was added. (B) Aggregation percentage tracing curve of ADP-induced platelet aggregation under 10−7 M 20-HETE or rofecoxib. Graphs represent the mean ± SEM, depicting the percentage of aggregation over 5 min (n = 6). The control (CTL) group contains neither rofecoxib nor 20-HETE. Each point represents the mean ± SD (n = 6). Statistical significance was determined by a two-sided unpaired t test and repeated measures one-way ANOVA (*P < 0.05; **P < 0.01).

Jun-Yan Liu, et al. Proc Natl Acad Sci U S A. 2010 September 28;107(39):17017-17022.
3.
Fig. 4.

Fig. 4. From: Metabolic profiling of murine plasma reveals an unexpected biomarker in rofecoxib-mediated cardiovascular events.

In vitro effects of 20-HETE and its COX-mediated metabolites on blood clotting time. Venous blood (25 μL) was collected from the tail of Swiss Webster mice (male, 8 wk of age) to test blood clotting time using prescored capillary tubes rinsed with DMSO, 20-HETE (0.5 mM in DMSO), 20-OH-PGE2 (0.5 mM in DMSO), or 20-OH-PGF (0.5 mM in DMSO). The final concentration of 20-HETE, 20-OH-PGE2, and 20-OH-PGF was calculated to be ≈13 μM. Each compound was tested with blood from six individual mice. Data represent the mean ± SD (n = 6). Statistical significance was determined by a two-sided unpaired t test and one-way ANOVA (*P < 0.05; **P < 0.01).

Jun-Yan Liu, et al. Proc Natl Acad Sci U S A. 2010 September 28;107(39):17017-17022.
4.
Fig. 2.

Fig. 2. From: Metabolic profiling of murine plasma reveals an unexpected biomarker in rofecoxib-mediated cardiovascular events.

Infusion of 20-HETE significantly shortened the murine tail bleeding time. (A) Infusion (s.c.) of 20-HETE for 3 wk leads to a significantly shortened tail bleeding time (n = 6). The tail bleeding time was measured before the mice were killed. If the bleeding time was more than 10 min, the experiment was terminated at 10 min and recorded as 10 min. (B) Infusion (s.c.) of 20-HETE for 3 wk results in a higher plasma level of 20-HETE (n = 6). Data represent the mean ± SD. 20-HETE was administered with s.c. infusion at a flow rate of 250 ng/h. The bleeding time is a parameter of blood coagulation. A shorter bleeding time means that the blood is easier to aggregate, which increases the risk for cardiovascular events. Statistical significance was determined by a two-sided unpaired t test and one-way ANOVA (**P < 0.01).

Jun-Yan Liu, et al. Proc Natl Acad Sci U S A. 2010 September 28;107(39):17017-17022.
5.
Fig. 1.

Fig. 1. From: Metabolic profiling of murine plasma reveals an unexpected biomarker in rofecoxib-mediated cardiovascular events.

Chronic administration of rofecoxib significantly increases the blood level of 20-HETE, leading to a dramatically shortened tail bleeding time. (A) Oral administration of rofecoxib for 3 mo results in a dramatically shortened tail bleeding time (n = 6). The tail bleeding time was measured before the mice were killed. If the bleeding time was more than 10 min, the experiment was terminated at 10 min and recorded as 10 min. (B) Oral administration of rofecoxib for 3 mo results in a dramatic increase in plasma levels of 20-HETE (n = 6; dotted line, quantitative limit). (C) Structures of rofecoxib and 20-HETE. Data represent the mean ± SD. Rofecoxib was provided in the drinking water at a concentration of 50 mg/L. The bleeding time is a parameter of blood aggregation. A shorter bleeding time means that the blood is easier to aggregate, which can increase the risk for cardiovascular events. Statistical significance was determined by a two-sided unpaired t test and one-way ANOVA (**P < 0.01).

Jun-Yan Liu, et al. Proc Natl Acad Sci U S A. 2010 September 28;107(39):17017-17022.

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