Correction of the Endothelial Function and the Hemostasis System Disorders with Ademethionin and Taurine in Model Associated with ADMA-Like Preeclampsia
Objective: The aim of this study is to evaluate the effectiveness of pharmacological correction of functional disorders of endothelial function and the hemostasis system with ademethionin and taurine in ADMA-like preeclampsia model as a serious problem of modern medicine.
Materials and methods: Simulation of ADMA-like preeclampsia was performed by intraperitoneal injection of L-NAME to females in the same doses for 7 days (14-20th days of pregnancy). Deficiency of nitric oxide in result of the blockade of NOsynthase was accompanied by violation of endothelium dependent and endothelium undependentvasodilation assessed in pharmacological trials, which was reflected in the increase of the coefficient endotelialny dysfunction. The platelet aggregation induced by ADP, collagen, ristomycin, adrenaline was determined, as well as PTT, TT, aPTT, fibrinogen, and the clotting time. The animals were divided into the following groups: Intact – pregnant + 0.9% NaCl from the 14th to the 20th days of pregnancy. (n=10); -NAME) – pregnant + ADMA-like agent (with intraperitoneal administration of L-NAME at a dose of 25 mg/kg once a day from the 14th to the 20th days of pregnancy) (n=10); Pregnant + L-NAME 25 mg/kg + Taurine (50 mg/kg/day orally) (n=10); Pregnant + L-NAME 25 mg/kg + Taurine (50 mg/kg/day orally) (n=10); Pregnant + L-NAME 25 mg/kg +Ademethionine (150 mg/kg/ day orally (n=10); Pregnant + L-NAME 25 mg/kg + Taurine (50 mg/kg/day orally) +Ademethionine (150 mg/kg/ day orally (n=10).
Results: Introduction of ademethionin and taurine resulted in a decrease in thrombocyte aggregation capacity from 53.8±2.60% to 27.7±1.25% when using ADP as an inducer. The clotting time was from 841±42 s up to 1152±25 s. In addition, there was an increase in temporal parameters of plasma-coagulation hemostasis and a decrease in plasma fibrinogen content. In the group with use of taurine the coefficient of endothelial dysfunction decreased to the level of intact animals. Use of ademethionine and taurine combined resulted in the most pronounced endothelioprotective effect on the ADMA-like preeclampsia model. The coefficient of endothelial dysfunction decreased more than when using monotherapy of these drugs.
Conclusion: In animals with experimental preeclampsia, there were disturbances in the hemostasis system, comparable to those in the clinical situation. The use of ademethionine and taurine leads to a pronounced correction of hemostasis parameters. Possibly, ademethionine and taurine have an endothelioprotective effect because of their ability to decrease hyperhomocysteinemia.