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The effect of some ε-aminocaproic acid derivatives on platelet responses.

100%

Bruzgo I., Tomasiak M., Stelmach H., Midura-Nowaczek K.

vol. 51

issue 1

73-80

ε-Aminocaproic acid (EACA) is a synthetic low molecular drug with antifibrinolytic activity. However, treatment with this drug can be incidentally associated with an increased thrombotic tendency. The aim of the present work was to test synthetic EACA derivatives for their antiplatelet activities. We investigated the effect of three EACA derivatives with antifibrinolytic activity: I. ε-aminocaproyl-L-leucine hydrochloride (HClH-EACA-L-Leu-OH), II. ε-aminocaproyl-L-(S-benzyl)-cysteine hydrochloride (HClH-EACA-L-Cys(S-Bzl)-OH) and III. ε-aminocaproyl-L-norleucine (H-EACA-L-Nle-OH) on platelet responses (aggregation and adhesion) and on their integrity. It was found that: 1. as judged by LDH release test, none of the tested compounds, up to 20 mM, was toxic to platelets, 2. in comparison with EACA, all the synthetic derivatives inhibited much stronger the ADP- and collagen-induced aggregation of platelets suspended in plasma (platelet rich plasma) and aggregation of these cells in whole blood, 3. EACA and its derivatives exerted a similar inhibitory effect on the thrombin-induced adhesion of platelets to fibrinogen-coated surfaces. Since platelet activation and blood coagulation are tightly associated processes, the antiplatelet properties of EACA derivatives are expected to indicate reduced thrombotic properties of these derivatives compared to EACA.

THE INHIBITION OF HUMAN PLATELET AGGREGATION BY A LOW-MOLECULAR WEIGHT CHITOSAN

88%

Drozd N. N., Logvinova Y. S., Shagdarova B. T., Il’ina A. V., Varlamov V. P.

vol. 23

55 - 65

Chitosan derivatives were obtained by chemical (MW of 6 kDa, DD 99% - Ch6/99; MW13 kDa, DD 98% - Ch13/98) and enzymatic (MW of 5 kDa, DD 85% - Ch5/85; MW of 10 kDa, DD 85% - Ch10/85) depolymeri-sation of chitosan with a MW of 334 and 1000 kDa. Chitosan derivatives (almost identical MW pairs and different DD) possessed insignificant an-ticoagulant activity, did not promote human platelet aggregation and re-duced ADP or collagen-induced platelet aggregation. The studied sam-ples at a concentration of 2 mg/ml reduced the aggregation of platelets more than twice induced in 2x10-6M and 1x10-5M concentrations; at weak activation in 2x10-6M, the Ch10/85 sample was the most effective. The Ch6/99 and Ch13/98 samples were 20 times more effective at the inhibi-tion of collagen-induced platelet aggregation than the Ch10/85 sample. The latter can be explained by the greater value of positive charge (DD) and polydispersity (Mw/Mn) of chitosan samples obtained by chemical de-polymerisation

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1 Acta Biochimica Polonica

1 Progress on Chemistry and Application of Chitin and its Derivatives

1 2018

1 2004

1 Bruzgo I.

1 Drozd N. N.

1 Il’ina A. V.

1 Logvinova Y. S.

1 Midura-Nowaczek K.

1 Shagdarova B. T.

1 Stelmach H.

1 Tomasiak M.

1 Varlamov V. P.

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The effect of some ε-aminocaproic acid derivatives on platelet responses.

THE INHIBITION OF HUMAN PLATELET AGGREGATION BY A LOW-MOLECULAR WEIGHT CHITOSAN