Metformin reduces platelet hypersensitivity in hypercholesterolemic rabbits.
The effects of Metformin treatment on platelet responsiveness to aggregating agents was studied in cholesterol-fed rabbits. Three groups of animals were fed, for one month, either a normal (N), or a hypercholesterolemic (HC), or a hypercholesterolemic + 0.5% Metformin diet (HC + Met), Platelets from the HC rabbits required significantly lower collagen and arachidonic acid concentrations to aggregate, as compared to platelets from N rabbits. The platelet response from the HC + Met rabbits was not significantly different from that of normals. The cholesterol/phospholipid ratio in platelets was increased in both dietary groups (HC, HC + Met). The serum thromboxane B2 concentrations did not show any significant difference between the groups. Plasma exchange experiments failed to indicate a specific effect of the plasma environment on platelet behaviour. In view of the inactivity of metformin on the platelet cyclo-oxygenase pathway, the reported results suggest that metformin may act by an as yet unexplored mechanism.
D000818:Animals; D001791:Blood Platelet Disorders / Q000188:drug therapy* / Q000209:etiology; D001792:Blood Platelets / Q000032:analysis / Q000187:drug effects; D002791:Cholesterol, Dietary / Q000494:pharmacology; D003094:Collagen / Q000494:pharmacology; D006937:Hypercholesterolemia / Q000150:complications*; D006967:Hypersensitivity / Q000188:drug therapy* / Q000209:etiology; D008055:Lipids / Q000097:blood; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D010951:Plasma Exchange; D010974:Platelet Aggregation; D011817:Rabbits; D013929:Thromboxane B2 / Q000097:blood
D002791:Cholesterol, Dietary; D008055:Lipids; D013929:Thromboxane B2; D003094:Collagen; D008687:Metformin