Study of endothelial dysfunction and asymmetric dimethylarginine levels
Keywords
experimental diabetic retinopathy, endothelial dysfunction, endothelin-1, Asymmetric dimethylarginine, correction, metformin, aflibercept, L-arginine, citicoline, L-carnitine, bromfenacAbstract
The aim of the study was to analyze changes in the level of endothelin-1 and asymmetric dimethylarginine in the development of endothelial dysfunction in experimental diabetic retinopathy and various methods of its correction.
The study was performed on white Wistar rats weighing 180-200 g. According to the tasks of the animal were divided into 7 groups:
As a result of our study proved a violation of the structural and functional state of the endothelium in experimental diabetic retinopathy, as evidenced by elevated levels of ADMA and endothelin-1 in 2nd group (p <0.001), most pronounced in the 3rd stage. It was confirmed that the correction of the studied complication of diabetes mellitus only with a hypoglycemic drug, even with long-term administration, does not correct the development of endothelial dysfunction (p <0.001).
It was found that the addition of aflibercept and a solution of L-arginine in the correction to hypoglycemic drugs significantly (p <0.001) improves the condition of the endothelium, but does not solve the problem completely. It is observed that the correction of the simulated pathological condition by reducing hyperglycemia, administration of aflibercept and bromfenac (group № 5) has a positive effect on the normalization of endothelial function markers (p <0.001), but the effect is less pronounced than in the following groups. It was found that in rats in which diabetic retinopathy was simulated with subsequent correction of hyperglycemia, administration of aflibercept, L-carnitine and bromfenac (group № 6), the reduction of pathologically elevated levels of markers of endothelial dysfunction is more pronounced compared to the 3rd group, which indicates the feasibility of this method of correction. It was found that the most effective method of correction was in the 7th group of the experiment in which hyperglycemia was corrected, aflibercept, L-arginine and citicoline were obtained to normalize the levels of endothelial dysfunction markers - endothelin 1 and asymmetric dimethylarginine.
References
Endothelial dysfunction in the pathogenesis of complications of diabetes. Message I. Endothelial dysfunction: etiology, pathogenesis and diagnostic methods AI Gozhenko, G.S. Kuznetsova, K.S. Kuznetsova, T.M. Beat, AB Wort. Endocrinology. 2017, T 22, No. 2. S. 171-181.
Sukhareva OY, Shestakova MV Modern standards and recommendations for the treatment of diabetes mellitus 2: focus on metformin // Consilium medicum. - 2009. - V. 11, No. 12. - P. 18-24.
Steinmetz A., Fenselau S., Schrezenmeir Y. Treatment of dyslipoproteinemia in the metabolic syndrome // Exp. Clin. Endocrinol. Diabetes. - 2001. - Vol. 109, No. 4. - P. 548-559.
Kuznetsova ES, Kuznetsova AS, Shukhtin VV, Gozhenko AI Features of the osmoregulatory function of the kidneys in patients with type 2 diabetes // Ukrainian Journal of Nephrology and Dialogue. - 2015. - No. 4 (49). - S. 21-26.
Kurkin D.V., Logvinova E.O., Bakulin D.A., Volotova E.V., Tyurenkov I.N. Endothelioprotective properties of the new gpr119 receptor agonist (dipiarone) in animals with chronic cerebrovascular accident and experimental diabetes mellitus // Modern problems of science and education. - 2018. - No. 4.; URL: http://www.science-education.ru/ru/article/view?id=27935 (date accessed: 09/06/2020).
Arkhipova M. M., Neroev V. V., Baratova L. A., Lysenko V. S. / / Bulletin of ophthalmology. - 2000. - No. 2. - P. 8-10.
Arkhipova MM, Vanin AF / / Bulletin of ophthalmology. - 2001. -No. 1 - S. 10-11.
The role of nitric oxide in the formation of endothelial dysfunction in diabetes mellitus. S.G. Dzugkoev, F.S. Dzugkoeva, V.A. Metelskaya. Cardiovascular therapy and prevention, 2010; 9 (8). C63-68.
Pasechnikova N.V., Moroz O.A. Protective action of quercetin and lipoate on functional groups of retinal proteins in diabetes modeling. Ophthalmological journal. - 2015. - No. 3. - P. 76-81
Bayrasheva V.K., Babenko A.Yu., Dmitriev Yu.V., Bayramov A.A., Chefu S.G., Shatalov I.S., Arefieva A.N., Pchelin I.Yu., Khudyakova N V.V., Aliev P.N., Grineva E.N. The role of metformin in the prevention of diabetic nephropathy in experimental type 2 diabetes mellitus. Regional blood circulation and microcirculation. 2016; 15 (3): 70-80.
Pokrovsky M.V., Pokrovskaya T.G., Korchakov V.I. et al. Endothelioprotective effects of L-arginine in modeling nitric oxide deficiency. Let's experiment. and a wedge. pharmacol. 2008; 71 (2): 29–31.
Efficacy of Subconjunctival Aflibercept Versus Bevacizumab for Prevention of Corneal Neovascularization in a Rat Model. Cornea. 2016 - Vol. 35 - Issue 7.P. 991-996.
Bykov I.L. The influence of L-carnitine on metabolic disorders in experimental deficiency of acyl-CoA dehydrogenases. Experimental and Clinical Pharmacology. 2004. - Volume 67 - No. 6. P.48-52.
Dzugkoev S. G. Dzugkoeva F. S. Gumanova N. G. Metelskaya V. A. The effect of coenzyme Q 10, afobazole and L-carnitine on endothelial function in rats with experimental diabetes mellitus. Kuban Scientific Medical Bulletin. 2012. - No. 3 (132). - S.48-51.
Lupan IV, Avramenko OV, Akbash KS Computer statistical packages: a basic methodical guide. - 2nd type. - Kirovohrad: "CODE" 2015. - 236 p.
Penishkevich Ya.I., Kuchuk O.P., Kuz'o OO, Clinical anatomy and operative surgery - T. 15, No. 2 - 2016. S. 114-116.
Xu FP Leptin induces hypertrophy via endothelin-1-reactive oxygen species pathway in cultured neonatal rat cardiomyocytes / FP Xu, MS Chen, YZ Wang // Circulation. - 2004. - Vol. 110. - P. 1269-1275.
Pataraya S.A. Biochemistry and physiology of the endothelin family / S.A. Pataraya, D.V. Preobrazhensky, B.A. Sidorenko // Cardiologist. - 2000. - No. 6. - S. 78-85.
Guidry C. Endothelins produced by endothelial cells promote collagen gel contraction by fibroblasts / C. Guidry, M. Hook // J. Cell. Biol. - 1991. - Vol. 115. - P. 873-880.
Belchina Yu. B. Endothelial condition in patients with type 1 diabetes mellitus and metabolic cardiomyopathy / Yu. B. Belchina, LK Sokolova // Liki Ukrainy. - 2013. - No. 4. - S. 65-68. - Access mode: http://nbuv.gov.ua/UJRN/likukr_2013_4_14
Galyavich A.S., Gainutdinov E.R. Asymmetric dimethylarginine and products of nitric oxide metabolism in patients with acute and chronic forms of ischemic heart disease. Cardiovascular therapy and prevention. 2009; 8 (1): 31-34.
Lu CW, Xiong Y, He P. Dimethylarginine dimethylaminohydr olase-2 overexpression improves impaired nitric oxide synthesis of endothelial cells induced by glycated protein. Nitric Oxide 2006; 8:
MacAllister RJ, Parry H, Kimoto M, et al. Regulation of nitric oxide synthesis by dimethylarginine dimethylaminohydrolase. Br J Pharmacol 1996; 119: 1533-40.
Bode-Boger SM, Scalera F, Martens-Lobenlioffer J. Asynmietric dimethylarginine (ADMA) accelerates cell senescence. Vase Med 2005; 10 (Suppl 1): S65-71.
Chan JR, Boger RH, Bode-Boger SM, et al. Asymmetric dimethylarginine increases mononuclear cell adhesiveness in hypercholesterolemic humans. Arterioscler Thromb Vase Biol 2000; 20: 1040-6.
Smirnova IV, Kajstura M, Sawamura T, et al. Asymmetric dimethylarginine upregulates TOX-1 in activated macrophages: role in foam cell formation. Am J Physiol Heart Circ Physiol 2004; 287: H782-9.
Boger RH, Bode-Boger SM, Szuba A, et al. Asymmetric dimethylarginine (ADMA): a novel risk factor for endothelial dysfunction: its role in hypercholesterolemia. Circulation 1998; 98: 1842-7.
Stuhlinger MC, Oka RK, Graf EE, et al. Endothelial dysfunction induced by hyperhomocyst (e) inemia: role of asymmetric dimethylarginine. Circulation 2003; 108: 933-8
Rodionov R.N., Blokhin I.O., Galagudza M.M., Shlyakhto E.V., Lentz S.R. Asymmetric dimethylarginine and its role in the etiology and pathogenesis of cardiovascular diseases. Arterial hypertension. 2008.-N 4.- S.306-314.
Boger RH, Cooke JP, and Vallance P. ADMA: an emerging cardiovascular risk factor. Vasc Med 2005; 10 Suppl 1: S1-S2.
Boger RH, Bode-Boger SM, Mugge A., Kienke S., Brandes R., Dwenger A., and Frolich JC Supplementation of hypercholesterolaemic rabbits with L-arginine reduces the vascular release of superoxide anions and restores NO production. Atherosclerosis 1995; 117: 273-284.
Boger RH Asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, explains the "L-arginine paradox" and acts as a novel cardiovascular risk factor. J Nutr 2004; 134: 2842S-2847S.
Pollock JS, Forstermann U., Mitchell JA, Warner TD, Schmidt HH, Nakane M., and Murad F. Purification and characterization of particulate endothelium-derived relaxing factor synthase from cultured and native bovine aortic endothelial cells. Proc Natl Acad Sci USA 1991; 88: 10480-10484.
Leiper J., and Vallance P. Biological significance of endogenous methylarginines that inhibit nitric oxide synthases. Cardiovasc Res 1999; 43: 542-548
Faraci FM, Brian JEJ, and Heistad DD Response of cerebral blood vessels to an endogenous inhibitor of nitric oxide synthase. Am J Physiol 1995; 269: H1522-H1527.
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