Pharmacological correction of L-name-induced oxide deficiency with derivatives of 3-(2,2,2-trimethylhydrazinium) propionate

Skachilova, Sophiya Ya.; Кесарев, О. Г.; Даниленко, Л. М.; Быстрова, Н. А.; Должиков, А. А.; Nikolaev, S.B.

doi:10.18413/2313-8971-2016-2-1-36-41

Cited by 3 publications

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“…In this case, their study should be conducted on pharmacological targets, which provides a targeted search for the creation of new drugs. [3][4][5] Today, different methods are proposed for the assessment of the cardioprotective activity of pharmacological agents: Check the absorption of calcium ions by isolated heart of rats, [6] the tests for the load resistance, [7,8] non-invasive evaluation of systolic function…”

Section: Introductionmentioning

confidence: 99%

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Даниленко¹

2018

AJP

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Introduction: At present, doxorubicin (DOX) is the most popular anthracycline antibiotic in oncology. The search for substances with a cardiotropic effect in DOX-associated cardiomyopathy is conducted among various classes of chemical and pharmacological groups. Research Tasks: Development of methodological approaches for evaluation of cardioprotective activity of drugs in doxorubicin cardiomyopathy. Materials and Methods: Simulation of the cardiomyopathy was performed by intraperitoneal administration of DOX at a dose of 20 mg/kg 1 time per day. After 48 h, we assessed indices of a left ventricular contractility under conditions of high heart rate 480 bmp for 15 s on an isolated Langendorff heart of rats. As an additional index of the assessment of the cardioprotective action of pharmacological agents, S tТТI coefficient was used, reflecting the diastole defect, which is an area under the curve of the buildup of an end diastolic pressure. To evaluate the myocardial damage, the isoenzyme creatine phosphokinase-MB and lactate dehydrogenase (LDH) in perfusate flowing from the isolated hearts were determined. For a comprehensive confirmation of the development of the simulated pathological processes, a morphological study of the hearts was performed. As drugs, enalaprilat (KRKA Slovenia) at the dose of 5 mg/kg intraperitoneally every 12 h, carvedilol (Teva, Israel) per os 1 time a day, and verapamil (JSC Alkaloid, Macedonia) at the dose of 5 mg/kg intraperitoneally 1 time a day were used. Results: In a control group with the DOX-induced cardiomyopathy under the conditions of submaximal stimulation frequencies (480 bpm), we observed the diastolic defect which numerically was S tТТI = 8.3 ± 0.3 c.u. which shows significant damage and the failure of the calcium pumps of cardiac myocytes. In an intact group, S tТТI coefficient was 1.4 ± 0.1 c.u. which is 8 times less than in the control group. The results of biochemical and morphological studies confirmed the degree of myocardial damage. In the comparative analysis of cardioprotective activity of drugs in doxorubicin cardiomyopathy, the studied compounds were located in the following sequence: Enalaprilat (5 mg/kg), carvedilol (30 mg/kg), verapamil (5 mg/kg). Conclusion: The fundamental difference in the area under the curve of the buildup of the end diastolic pressure under the conditions of submaximal stimulation frequencies (480 bpm) for 15 s in the intact group and the control group on the background of DOX administration naturally led to the necessity of introducing S tТТI coefficient, which is quite revealing and informative. The obtained results allow to use S tТТI at the screening of innovative molecules.

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Section: Introductionmentioning

confidence: 99%

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Даниленко¹

2018

AJP

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The role of iNOS inhibition in the mechanism of the cardioprotective effect of new GABA and glutamic acid derivatives in the model of acute alcoholic myocardial injury in rats

et al. 2023

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The cardioprotective effects of new derivatives of glutamic acid (glufimet) and GABA (mefargin) were studied in rats exposed to acute alcohol intoxication (AAI) under conditions of selective blockade of inducible NO-synthase (iNOS). AAI induced a pronounced decrease in the contractile function of the myocardium during exercise tests (load by volume, test for adrenoreactivity, isometric exercise), caused mitochondrial dysfunction and increased processes of lipid peroxidation (LPO) in heart cells. A decrease in NO production during iNOS inhibition and AAI improved the respiratory function of mitochondria, a decreased the level of LPO products, and increased mitochondrial superoxide dismutase activity of heart cells. This led to an increase in myocardial contractility. The studied compounds, glufimet and mefargin, caused a statistically significant increase in the rates of myocardial contraction and relaxation, left ventricular pressure, and also reduced NO production. This was accompanied by a decrease in the intensity of LPO processes and an increase in the respiratory control ratio (RCR), reflecting the coupling between respiration and phosphorylation processes during activation of the respiratory chain complexes I and II. The decrease in NO concentration during selective blockade of iNOS and administration of the studied substances was less pronounced than without blockade of the enzyme. This suggests the putative effect of new derivatives of neuroactive amino acids on the NO system.

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Study of Efficiency of 3-Oxypiridine Derivatives in Correction of Disorders in the Conditions of Experimental Preeclampsia

Yurakova

Skachilova²,

Даниленко

et al. 2020

Journal of Volgograd State Medical University

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The pathogenesis of preeclampsia is polyetiologic and not fully understood. One of the leading theories of pathogenesis is the theory of oxidative stress. Accordingly, the search for new drugs with antioxidant and antihypoxic effects is promising for the prevention and treatment of preeclampsia. Methods. The experiment was performed on 140 female white rats of Wistar strain weighing 250-300 g. The studied substances were administered within 7 days from 14 to 21 days of pregnancy. On the 21st day of pregnancy, functional tests were conducted. Results. Administration of 3-oxypiridine derivates in animals causes the expressed correction of pathological changes in experimental ADMA-like preeclampsia. There was a significant rise in systolic and diastolic blood pressure, respectively, the improvement of microcirculation in the placenta, restoration of endothelium NO-synthesis function, proteinuria reduction. Conclusion. The results of this study prove the future outlook of the use of 3-oxypiridine derivates for correction of functional changes in preeclampsia and substantiate the reasonability of further research in this direction.

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Pharmacological correction of L-name-induced oxide deficiency with derivatives of 3-(2,2,2-trimethylhydrazinium) propionate

Cited by 3 publications

References 0 publications

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The role of iNOS inhibition in the mechanism of the cardioprotective effect of new GABA and glutamic acid derivatives in the model of acute alcoholic myocardial injury in rats

Study of Efficiency of 3-Oxypiridine Derivatives in Correction of Disorders in the Conditions of Experimental Preeclampsia

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