Antiplatelet activity of alpha-lipoic acid.
Alpha-lipoic acid (ALA) is often used as a dietary supplement to prevent and treat chronic diseases associated with excessive oxidative stress. The aim of this study was to investigate the mechanisms of the antiplatelet activity of ALA. ALA significantly inhibited collagen-induced platelet aggregation, thromboxane B(2) (TXB(2)) formation, Ca(2+) mobilization, and protein kinase Calpha (PKCalpha) activation, but ALA itself increased cyclic AMP formation in rabbit washed platelets. However, the effects of ALA on the above platelet responses were markedly reversed by the addition of 2'5'-ddAdo, an adenylate cyclase inhibitor. Additionally, increased reactive oxygen species (ROS) formation and cyclooxygenase-1 activity stimulated by arachidonic acid were inhibited by ALA. In conclusion, we demonstrated that ALA possesses an antiplatelet activity, which may be associated with an elevation of cyclic AMP formation, involving subsequent inhibition of TXA(2), Ca(2+) mobilization, and PKCalpha-mediated pathways. Moreover, inhibition of ROS formation and increase of platelet membrane fluidity may also involve its actions.
Lai
Yuan-Shu
YS
Taipei City Hospital, Taipei, Taiwan.
Shih
Ching-Yu
CY
Huang
Yu-Feng
YF
Chou
Tz-Chong
TC
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D051545:Cyclooxygenase 1 / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism; D008063:Thioctic Acid / Q000494:pharmacology*
D010975:Platelet Aggregation Inhibitors; D017382:Reactive Oxygen Species; D008063:Thioctic Acid; D000242:Cyclic AMP; D051545:Cyclooxygenase 1