Modulatory influence of sodium 2-propenyl thiosulfate from garlic on cyclooxygenase activity in canine platelets: possible mechanism for the anti-aggregatory effect.
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.
Chang
H S
HS
Laboratory of Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, 060-0818, Japan.
Yamato
O
O
Yamasaki
M
M
Maede
Y
Y
D000498:Allyl Compounds / Q000494:pharmacology*; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D051545:Cyclooxygenase 1; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005737:Garlic / Q000737:chemistry*; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins; D010084:Oxidation-Reduction; D010936:Plant Extracts / Q000494:pharmacology; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000302:isolation & purification / Q000378:metabolism*; D013463:Sulfuric Acid Esters / Q000494:pharmacology*
C488464:2-propenyl thiosulfate; D000498:Allyl Compounds; D008565:Membrane Proteins; D010936:Plant Extracts; D010975:Platelet Aggregation Inhibitors; D013463:Sulfuric Acid Esters; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D005978:Glutathione