Modulatory influence of sodium 2-propenyl thiosulfate from garlic on cyclooxygenase activity in canine platelets: Possible mechanism for the anti-aggregatory effect

Modulatory influence of sodium 2-propenyl thiosulfate from garlic on cyclooxygenase activity in canine platelets: Possible mechanism for the anti-aggregatory effect
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DOI:
10.1016/j.plefa.2005.01.003
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发表时间:
2005-05-01
影响因子:
3
通讯作者:
Maede, Y
Maede, Y
中科院分区:
医学4区
文献类型:
--
作者:
Chang, HS;Yamato, O;Maede, Y

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我们以前发现2-丙烯基硫代硫酸钠(2 PTS)在相对低浓度下对犬和人血小板都具有体外抗聚集作用,但在高浓度下聚集程度趋于恢复到对照水平。为了阐明2 PTS调节血小板聚集的机制,我们研究了2 PTS对犬血小板环氧化酶(考克斯)活性和还原型谷胱甘肽(GSH)浓度的影响。血小板考克斯酶活性在0.1 mM浓度下呈剂量依赖性抑制,但在1 mM浓度下趋于恢复到对照水平,而血小板GSH浓度则呈剂量依赖性降低,在0.1 mM(P < 0.05)和1 mM(P < 0.001)浓度下显著降低。此外,纯化的考克斯-1的活性直接抑制GSH的加入以剂量依赖性的方式。根据这些结果,我们得出结论,2 PTS诱导的血小板聚集抑制是由于抑制考克斯活性而发生的。此外,2 PTS可能通过影响血小板GSH浓度而对血小板聚集具有调节作用。(c)2005爱思唯尔有限公司保留所有权利。
We previously found that sodium 2-propenyl thiosulfate (2PTS) has an anti-aggregatory effect in vitro on both canine and human platelets at relatively low concentrations, but the extent of aggregation tends to return to the control level at high concentrations. To clarify the mechanism of this modulatory influence of 2PTS on the aggregation of platelets, we investigated the effects of 2PTS on cyclooxygenase (COX) activity and the reduced glutathione (GSH) concentration in canine platelets. Platelet COX activity was inhibited by 2PTS in a dose-dependent manner up to 0.1 mM, but tended to return to the control level at 1 mM. In contrast, the platelet GSH concentration decreased in a dose-dependent manner after treatment with 2PTS and a significant decrease was observed at 0.1 mM (P < 0.05) and 1 mM (P < 0.001). Furthermore, the activity of purified COX-1 was directly inhibited by addition of GSH in a dose-dependent manner. From these results, we conclude that the 2PTS-induced inhibition of platelet aggregation occurs as a result of inhibition of COX activity. Additionally, 2PTS may have a modulatory effect on platelet aggregation by affecting the platelet GSH concentration. (c) 2005 Elsevier Ltd. All rights reserved.