Selective conjugated fatty acids inhibit guinea pig platelet aggregation

Selective conjugated fatty acids inhibit guinea pig platelet aggregation
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DOI:
10.1016/j.ejphar.2006.06.059
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发表时间:
2006-09-18
影响因子:
5
通讯作者:
Cook, Mark E.
Cook, Mark E.
中科院分区:
医学2区
文献类型:
--
作者:
Li, Guangming;Butz, Daniel;Cook, Mark E.

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共轭亚油酸已显示减少从选择的组织和/或细胞释放类二十烷酸。为了阐明共轭亚油酸异构体对环氧合酶-1(考克斯-1)活性的影响及其作为血小板聚集抑制剂的应用,将共轭亚油酸异构体和共轭十九碳二烯酸与绵羊考克斯-1和Raw 264.7巨噬细胞一起孵育,以检查它们对考克斯-1活性的影响。在胶原和ADP诱导的豚鼠全血血小板聚集中进一步检查了效果。测试的脂肪酸显示出抑制考克斯-1酶活性。然而,只有10 t,12 c-共轭亚油酸、9 t,11 t-共轭亚油酸和共轭十九碳二烯酸抑制胶原和ADP诱导的血小板聚集,IC 50为125.9 μ M(74.2 μ M至213.4 μ M,95%置信区间),99.3 μ M在胶原蛋白诱导的聚集中分别为52.8 μ M至187.2 μ M,95%置信区间)和124.3 μ M(85.1 μ M至181.5 μ M,95%置信区间)。10 t,12 c-共轭亚油酸、9 t,11 t-共轭亚油酸和共轭十九碳二烯酸也明显抑制TxB(2)的释放。10 t,12 c-共轭亚油酸、9 t,11 t-共轭亚油酸和共轭十九碳二烯酸是血小板聚集抑制剂,9 c,11 t-共轭亚油酸是中度抑制剂,亚油酸和9 c,11 c-共轭亚油酸对血小板聚集无影响。(c)2006 Elsevier B. V.保留所有权利。
Conjugated linoleic acids have been shown to reduce eicosanoid release from select tissues and/or cells. To elucidate effects of conjugated linoleic acid isomers on cyclooxygenase-1 (COX-1) activity and their application as platelet aggregation inhibitors, conjugated linoleic acid isomers and conjugated nonadecadienoic acid were incubated with ovine COX-1 and Raw264.7 macrophage to examine their effects on COX-1 activity. The effects were further examined in collagen and ADP-induced guinea pig whole blood platelet aggregation. Fatty acids tested were shown to inhibit COX-1 enzymatic activity. However, only 10t, 12c-conjugated linoleic acid, 9t, 11t-conjugated linoleic acid and conjugated nonadecadienoic acid inhibited collagen and ADP-induced platelet aggregation with IC50 125.9 mu M (74.2 mu M to 213.4 mu M, 95% confidence interval), 99.3 mu M (52.8 mu M to 187.2 mu M, 95% confidence interval) and 124.3 mu M (85.1 mu M to 181.5 mu M, 95% confidence interval) respectively in collagen-induced aggregation. TxB(2) release was also appreciably inhibited by 10t, 12c-conjugated linoleic acid, 9t, 11t-conjugated linoleic acid and conjugated nonadecadienoic acid. Based on these data, we conclude 10t, 12c-conjugated linoleic acid, 9t, 11t-conjugated linoleic acid and conjugated nonadecadienoic acid are platelet aggregation inhibitors while 9c, 11t-conjugated linoleic acid is a moderate inhibitor and linoleic acid, and 9c, 11c-conjugated linoleic acid have no effect on whole blood platelet aggregation. (c) 2006 Elsevier B.V. All rights reserved.