Антиоксидантна та енерготропна дія селективних модуляторів естрогенових рецепторів в умовах моделювання гострого інфаркту міокарда

Abstract

The purpose of the study is to take a closer look into the SERM antioxidant and energotropic activity in the simulated acute myocardial infarction. Materials and Methods. Small-focal acute myocardial infarction was simulated by the 3-day administration to rats of coronary spasmodic agent — pituitrin, and β1, 2, 3 adrenoceptor against isoprenaline. The study drugs were injected intraperitoneally 20 minutes after the injection of isadrine for three days. The concentration of nitrosyrosine, homocysteine, the activity of superoxide dismutase were detected in the heart homogenate, and of ST2 — in the blood plasma. The state of carbohydrate- energy metabolism was determined by the level of the most significant intermediates — ATP, ADP, AMP, lactate, pyruvate, malate, isocitrate, glycogen, as well as by the activity of cytosolic and mitochondrial creatine phosphokinase (CPK-ct; CPK-mx). Results and discussion. Experimental therapy of AMI wth the study drugs has led to a certain decrease in the heart rate, a decrease in the ST deflection, as well as promoted the recovery of the T-wave amplitude up to the test level, which has revealed their anti-ischemic effect. Statistically significant differences among the study drugs have not been recorded, as of their effect on ECG markers. Along with ECG changes, we have documented the oxidative stress development and the thiol-disulfide shift in the tissues of animals with AMI. Experimental therapy with tamoxifen, toremifene, and referent drugs — thiotriazolin and cаpicor, has led to statistically significant rise of SOD and GR comparing to corresponding terms of model pathology. The study drugs positive effect on the content of oxidative stress marker products has been detected, which occurred as the decrease in the number of thiol-disulfide oxidized derivatives — homocysteine and NТZ. In addition, the study drugs administration led to the stabilization of cardiomyocyte energy metabolism. An important factor is that experimental therapy did not only lead to energy production increase, but also to its transport, which was manifested in the rise of mitochondrial creatine phosphokinase (CPK-mx) activity. Toremifene and tamoxifen proved to have the most expressed effect in relation to this enzyme activity, increasing it on average by 56 per cent. Besides, experimental therapy led to a decrease in CPK-mx hyperenzymemia and marker ST2 concentration in the plasma. Experimental research has established that toremifene and tamoxifen selective estrogen receptor modulators possessed the most pronounced effect in the simulated acute myocardial infarction. The cardioprotective effects of selective estrogen receptor modulators documented by us are the experimental justification for the relevance and prospects of further research in this direction.