ד"ר יואב מיניסטר - Allicin and disulfiram enhance platelet integrin αIIbβ3-fibrinogen binding

מבוסס על מאמרים של  ד"ר יואב מיניסטר, בוריס שנקמן, נורית רוזנברג ונפתלי סביון

Integrins play an important role in cell-cell interactions. The integrin ?IIb?3 (glycoprotein IIbIIIa) found in platelet fibrinogen receptor is a good model to study this phenomenon. Binding of a ligand activates these integrins to induce their clustering and cytoskeletal rearrangement, which results in platelet aggregation leading to thrombosis. The biologically active compound of garlic, Allicin, has highly active disulfide bond [-S(O)-S-] and is known to be antimicrobial, hypolipidemic, anticancer, and antithrombotic. Allicin can react with different proteins with sulfhydryl (-SH) group to block their free sulfhydryl residues thus preventing disulfide bonds formation. Both ?IIb and ?3 integrin subunits of integrin have disulfide bonds forming cysteine residues and free sulfhydryls groups. Various experiments have suggested that by preventing disulfide bond formation in ?IIb?3 molecule, its binding with various ligands can be increased thus reducing platelet aggregation. In this study, platelet aggregation was induced by treatment with collagen or ADP and epinephrine, to check the effect of sulfhydryl-reactive agents like such as allicin, glutathione, dithiobis nitrobenzoic acid (DTNB) and disulfiram, on ?IIb?3 activity. Allicin and disulfiram are similar in structure and properties and have same ability to cross cell membrane whereas DTNB has an aromatic ring and can not cross the membrane and therefore is less effective than Allicin and disulfiram, which are more accessible to platelets to react with their sulfhydryls groups. Allicin was able to inhibit the aggregation of washed platelets when treated with aggregation-inducing agents. Both allicin and disulfiram could decrease the binding of ?IIb?3 with fibrinogen and bring down expression of P-selectin molecule in washed platelets, thus preventing platelet aggregation. These effects could be obtained by a plasma concentration of Allicin that can be achieved by consuming 4-5 garlic cloves per day, thus suggesting an effective measure to prevent thrombosis. Also it proves the efficacy of similar organosulfur compounds in cancer.