Study of vasodilation processes
DOI:
https://doi.org/10.12775/JEHS.2019.09.12.033Keywords
experimental diabetic retinopathy, endothelial dysfunction, vasodilation, S-nitrosothiols, correction, metformin, aflibercept, L-arginine, citicoline, L-carnitine, bromfenacAbstract
To date, the key role of endothelial dysfunction in the occurrence and progression of diabetes mellitus and diabetic retinopathy has been proven. The study was performed on white Wistar rats weighing 180-200 g. According to the tasks, the animals were divided into 7 groups. Our results indicate a violation of vasodilation on the 30th day of experimental diabetic retinopathy with subsequent progression of pathological changes on the 60th and 180th day of the study, as evidenced by a decrease in the content of S-nitrosothiols in group 2 (p <0,001 ), most pronounced in the 3rd stage. When analyzing the data of group № 3, it was found that the correction of the pathological condition with the help of hypoglycemic agents has some positive effect, but does not allow to significantly adjust the pathological development of reduced vasodilatory potential. The results of the 4th group indicate that the involvement of nitric oxide donor and aflibercept in the correction of diabetic retinopathy corrects the pathological changes and helps to restore the physiological pathway of nitric oxide synthesis and vascular tone, the maximum effect is observed on the 180th day of the experiment, but normative cannot be achieved. It is observed that the correction of the simulated pathological condition by reducing hyperglycemia, administration of aflibercept and bromfenac (group № 5) gives positive results in the first stage, but less pronounced than involvement in the complex correction of L-arginine solution in subsequent stages. It was found that rats in which diabetic retinopathy was simulated with subsequent correction of hyperglycemia, administration of aflibercept, L-carnitine and bromfenac (group № 6) have a pronounced tendency to normalize the studied marker of hypoxia in comparison with the previous methods in the second stage. nitrosothiols at the time of reaching the 3rd stage is reduced. The obtained data suggest that the method of correction chosen in group 7 (correction of hyperglycemia, aflibercept, L-arginine and citicoline solution) more pronouncedly normalizes the content of the vasodilation marker compared to other groups of our experiment, which is pronounced in long-term correction - on 180th day.
References
Vorobieva IV, Repkina M. Yu. Practical recommendations on observation of patients with diabetic retinopathy // Breast Cancer. Endocrinology. - 2009. - V. 17, № 24. - P. 1591-1595.
Astakhov Yu. S., Zaleskaya AG, Karpova IA, et al. Factors influencing the progression of diabetic retinopathy in patients withdiabetes type 2mellitus after transfer to insulin therapy // Clinical Ophthalmology. - 2005. - V. 6, № 3. - P. 110-114.
Abbate M, Cravedi P, Iliev I, et al. Prevention and treatment of diabetic retinopathy: evidence from clinical trials and perspectives // Curr Diabetes Rev. - 2011. - Vol. 7. - P. 190-200.
Vorobieva IV, Gigineishvili DN The role of endothelial dysfunction in the pathogenesis of diabetic retinopathy in patients with type 2 diabetes mellitus. Review. Ophthalmology. 2012; 9 (3): 9-13.
American Diabetes Association: Standards of medical care in diabetes-2011 // Diabetes care. - 2011. - Vol. 34, Suppl. I: S4–88.
Shestakova MV, Shamkhalova M. Sh. The modern approach to prevention and treatment of diabetic retinopathy: results of research DIRECT, 2009. Handbook of the polyclinic doctor. - 2009. - № 1. - P. 3-39.
Delano FA, Chen AY, Wu KI, et al. The autodigestion hypothesis and receptor cleavage in diabetes and hypertension // Drug Discov Today Dis Models. -2011. - Vol. 8. - P. 37-46.
Wright AD; Dodson PM. Diabetic Retinopathy and Blockade of the Renin Angiotensin System: New Data from the DIRECT Study Program // Eye. 2010. Vol. 24. - P. 1-6.
Porta M, Maldari P, Mazzaglia F. New approaches to the treatment of diabetic retinopathy // Diabetes Obes Metab. - 2011. - Vol. 13. - P. 784-790.
Gavrilova NA, Tishchenko OE Influence of sulodexide on the functional state of the endothelium in patients with diabetes mellitus and diabetic retinopathy // Diabetes mellitus. 2011. № 2. S. 66–68.
Astakhov YS, Shadrichev FE, Lisochkina AB Diabetic retinopathy // Ophthalmology - 2006. Clinical recommendations / ed. L.K. Moshetova, A.P. Nesterova, EA Egorova. M .: GEOTAR-Media, 2006. S. 139–163.
Kasatkina SG, Kasatkin SN Significance of endothelial dysfunction in patients with type 2 diabetes mellitus // Fundamental research. - 2011. - № 7 - P. 248-252.
Neroev VV, Sarygina OI, Levkina OA The role of vascular endothelial growth factor in the pathogenesis of diabetic retinopathy // Bulletin of Ophthalmology. - 2009. - № 2. - P. 58-60.
Koledintsev MN, Verzin RA The role of correction of the state of the endothelium and basement membrane of the vascular wall in diabetic retinopathy // Effective pharmacotherapy. Endocrinology.- 43 / 2015.-№5.
Pasechnikova NV Protective action of quercetin and lipoate on functional groups of retinal proteins in modeling diabetes / NV Pasechnikova. O.А. Moroz // Ophthalmological Journal. - 2015. - № 3. - P. 76-81
The role of metformin in the prevention of diabetic nephropathy in experimental type 2 diabetes mellitus / V.K. Bayrasheva, A. Yu.Babenko, Yu.V. Dmitriev, AA Bayramov, SG Chefu, I.S. Shatalov, AN Arefieva, I.Yu. Aliev, EN Grineva // Regional blood circulation and microcirculation. - 2016. - №15 (3). - P.70-80.
Pokrovsky MV Endothelioprotective effects of L-arginine in modeling nitric oxide deficiency / M.V. Pokrovsky, TG Pokrovskaya VI Korchakov // Experimental and clinical pharmacology. - 2008. - № 71 (2). - P. 29–31.
Efficacy of Subconjunctival Aflibercept Versus Bevacizumab for Prevention of Corneal Neovascularization in a Rat Model / Orly Gal-Or 1, Eitan Livny, Ruti Sella, Yael Nisgav, Dov Weinberger, Tami Livnat, Irit Bahar // Cornea. - 2016. - Vol. 3. - Issue 7. - R. 991-996.
Bykov IL Influence of L-carnitine on metabolic disorders in experimental insufficiency of acyl-CoA dehydrogenases / IL Bykov // Experimental and clinical pharmacology.-2004. -Volume 67 - № 6. P.48-52.
Dzugkoev SG Influence of coenzyme Q 10, afobazole and L-carnitine on endothelial function in rats with experimental diabetes mellitus / S.G. Dzugkoev, FS Dzugkoeva, NV Gumanova, В.А. Metelskaya // Kuban Scientific Medical Bulletin. - 2012. - №3 (132). - P.48-51.
Kovaleva OM, Demidenko GV, Gorbach TV Diagnosis of endothelial function - assessment of vasoactive nitric oxide pool // Ministry of Health of Ukraine. Ukrainian Center for Scientific Medical Information and Patent and License Work. Guidelines. Kyiv, publishing house SPD FO Tarasenko VP- 2007.-16 p.
Yunusov VYU. Morphofunctional features of blood vessels of descendants of smoking parents: dis. Cand. honey. Sciences: 14.03.04 Pathological physiology. Kharkiv. nat. honey. un-t. Kharkiv, 2016.
Lupan IV, Avramenko OV, Akbash KS Computer statistical packages: a textbook. - 2nd type. - Kirovograd: "CODE" 2015. - 236 p.
Vanin AF Dinitrosyl iron complexes and S-nitrosothiols are two possible forms of stabilization and transport of nitric oxide in biosystems. // Biochemistry, - 1998. v. 63. - issue. 7. - p. 924-938
Vanin AF, Malenkova IV, Serezhencov VA Iron catalyzes both decomposition and synthesis of S-nitrosothiols: optical and electron paramagnetic resonance studies. // Nitric oxide: Biology and Chemistry - 1997. - v.3. - p.191-203.
Roy B., Lepoivre M., HenryY., Fontecare M. Inhibition of ribonucleotide reductase by nitric oxide derived from thionitrites: Reversible modification of both subunits. // Biochemistry - 1995. -v.34. - p.5411 -5420.
Palmer, LA S-Nitrosothiols signal hypoxia-mimetic vascular pathology / LA Palmer, A. Doctor, P. Chhabra, ML Sheram, VE Laubach, MZ Karlinsey, MS Forbes, T. Macdonald, B. Gaston // J. Clin . Invest. - 2007. - Vol. 117. № 9. ó P. 2592–2601.
Gow, A. S-Nitrosothiol measurements in biological systems / A. Gow, A. Doctor, J. Mannick, B. Gaston // J. Chromatogr. B. - 2007. - Vol. 851. - № 1-2. - P. 140–151.
Patel RP S-Nitrosothiols and Nitric Oxide Biology / RP Patel, S. Yuan, CG Kevil // Nitric Oxide: biology and pathobiology: third edition. Elsevier Inc., - 2017. - P. 45–56.
Ignarro, LJ Nitric oxide as a unique signaling molecule in the vascular system: a historical overview / LJ Ignarro // J. Physiol. Pharmacol. - 2002. - Vol. 53. –№ 4. - P. 503–514.
Gow, AJ Immunohistochemical detection of S-nitrosylated proteins / AJ Gow, CW Davis, D. Munson, H. Ischiropoulos // Methods Mol. Biol. - 2004. - Vol.279. - P. 167–172.
М.В. Kruchinina, В.М. Generalov, A.S. Buryak, VN Kruchinin. Erythrocytes and no: facts, interaction hypotheses, prospects for diagnosis and therapy of cardiovascular diseases. Atherosclerosis. 2014. T. 10, № 3.S.68-80
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