Studying dose-dependent endothelio- and cardioprotective activity of selective arginase II inhibitor in hyperhomocysteine-induced endothelial dysfunction

Yakushev, V. I.; Филиппенко, Н. Г.; Kizilova, Irina; Корокин, М. В.; Бесхмельницына, Е. А.; Litvinova, Anna

doi:10.18413/2313-8971-2016-2-1-42-45

Cited by 5 publications

(3 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Preeclampsia currently remains an urgent problem of the modern obstetrics, as this complication is one of the most common causes of maternal and perinatal mortality worldwide. The frequency of this complication ranges from 2 to 8% of pregnancies (Gureev et al 2014;Adamyan et al 2016;Yakushev et al 2016). The recent studies have named a disruption of the functional state of the vascular endothelium among the main causes of the development of preeclampsia, which entails the development of the generalized vascular spasm, an increase in blood pressure, as well as disorders in the hemostasis system and, as a consequence, ischemic disorders in organs (Nguyen et al 2016;Lukyanova et al 2018).…”

Section: Introductionmentioning

confidence: 99%

Study of the effect of acetylsalicylic acid and a selective arginase II inhibitor KUD 975 on the correction of hemostatic disorders in experimental preeclampsia

Gureeva

Severinova

Гуреев

et al. 2022

RRP

View full text Add to dashboard Cite

Introduction: The disruption of the functional state of the vascular endothelium is among the main causes of preeclampsia, which is one of the most common causes of maternal and perinatal mortality. It can be enhanced by the humoral factors secreted by the activated platelets. The use of acetylsalicylic acid is an effective way to prevent preeclampsia. However, its ability to activate eNOS is a prerequisite for researching its ability to correct the disorders in developing preeclampsia, including by reducing the platelet activity. In this case its effect can be enhanced through increasing the bioavailability of L-arginine by using a selective arginase II inhibitor KUD 975. These facts were the prerequisite for conducting this study. Materials and methods: The study was conducted on 180 female Wistar rats weighing 250–300 g. Acetylsalicylic acid was used at a dose of 7 mg/kg/day and 10 mg/kg/day, KUD 975 – at a dose of 1 mg/kg/day and 3 mg/kg/day. Adenosine diphosphate (ADP, 6.5 microns), arachidonic acid (ASPI, 0.5 mM), and collagen (3.2 mcg/ml) were used as aggregation inducers. Results and discussion: ADMA-like preeclampsia simulation led to an increase in platelet aggregation ability when using all aggregation inducers. This is evidenced by an increase in a degree, rate of aggregation, and a shortened time of thrombus formation. The use of acetylsalicylic acid and a selective arginase II inhibitor KUD 975 led to a decrease in the aggregation ability of platelets and an increase in thrombosis time, while the combined administration of the studied agents showed a more pronounced effect. Conclusion: The data obtained while performing a series of experiments strongly indicate a promising outlook for using acetylsalicylic acid and a selective arginase II inhibitor KUD 975 in order to correct emerging disorders in preeclampsia.

show abstract

Section: Introductionmentioning

confidence: 99%

Study of the effect of acetylsalicylic acid and a selective arginase II inhibitor KUD 975 on the correction of hemostatic disorders in experimental preeclampsia

Gureeva

Severinova

Гуреев

et al. 2022

RRP

View full text Add to dashboard Cite

show abstract

“…At the same time, none of the proposed methods and their combinations provide guaranteed protection against ischemia-reperfusion injury, in connection with which the search and selection of innovative and promising compounds and preparations of this orientation continue. Preclinical studies at the systemic (Korokin et al, 2014;Peresypkina et al, 2016;Yakushev et al, 2016), cellular (Danilenko et al, 2016;Kravchenko et al, 2016;Kalmikov et al, 2018), and molecular (Bogus et al, 2018;Dzhimak et al, 2018;Soldativ et al, 2018) levels, including specific activity (Gumanova et al, 2007;Denisyuk et al, 2016;Danilenko, 2018) and toxicology studies (Kolesnichenko et al, 2018) in conjunction with bioequivalence studies )Kalmikov et al, 2018(, therapeutic equivalence and effectiveness (Avdeeva et al, 2016) are an integral part of the research of innovative drugs.…”

Section: Introductionmentioning

confidence: 99%

Incretin Mimetics Vildagliptin and Exenatide Improve Pedicle Skin Flap Survival in Rats.

Даниленко¹,

Tarasova²,

Pokrovskiy³

et al. 2019

jwpr

View full text Add to dashboard Cite

Hypoxia and tissue ischemia are the leading factors in the alteration of tissues in many pathological conditions. Prevention and reversion of the effects of local ischemia, which develops during various surgical interventions, is an actual problem of modern medicine. The aim of the present study was to investigate the effect of exenatide and vildagliptin on the survival rate of an isolated pedicle skin flap in sixty adults Wistar rats. Simulation of a pedicle skin graft was performed on the second day of the experiment. After anesthesia under aseptic conditions, a skin graft was cut out: isolated in a plastic bag, the edges of the skin were stitched with interrupted sutures (nylon 3/0). Rats were divided into six groups: control group, exenatide group (10 µg/kg/day subcutaneously for nine days after surgery), vildagliptin group (0.2 mg/kg/day intraperitoneally for nine days after surgery) and pentoxifylline group (100 mg/kg/day intravenously, two hours before the surgical intervention). In the other two groups, glibenclamide (5 mg/kg) were administered before injection of incretin mimetics. On the third, seventh and tenth day, area of the surviving tissue was measured. Subsequently, the survival rate of the skin graft was calculated. The area of the surviving tissue in exenatide and vildagliptin group was 1.5 and 1.7 times more compared to the control group, respectively. Preliminary blockade of ATP-dependent potassium channels by glibenclamide eliminated the protective effect of exenatide and vildagliptin. The increase in the survival of ischemic tissues using exenatide and vildagliptin has been experimentally proved. The current study confirmed the important role of ATP-dependent potassium channels in dermatoprotective properties of incretin mimetics.

show abstract

“…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%

Untitled

Даниленко¹

2018

AJP

View full text Add to dashboard Cite

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.

show abstract

Studying dose-dependent endothelio- and cardioprotective activity of selective arginase II inhibitor in hyperhomocysteine-induced endothelial dysfunction

Cited by 5 publications

References 0 publications

Study of the effect of acetylsalicylic acid and a selective arginase II inhibitor KUD 975 on the correction of hemostatic disorders in experimental preeclampsia

Study of the effect of acetylsalicylic acid and a selective arginase II inhibitor KUD 975 on the correction of hemostatic disorders in experimental preeclampsia

Incretin Mimetics Vildagliptin and Exenatide Improve Pedicle Skin Flap Survival in Rats.

Untitled

Contact Info

Product

Resources

About