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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2016; 62(6): 34-42


I.А. Palagina, M.Y. Kudria, О.S. Lаlymеnkо

    V.Y. Danilevsky Institute of Endocrine Pathology Problems, AMS of Ukraine, Kharkiv


We investigated the role of changes in the endogenous nitric oxide (NO) metabolism during the influence of succinic acid amides as biotransformation products of an anti-diabetic drug on the state of hemostasis. In experiment with rats, synthetic succinamides were applied in quantities equimolar to the sub-toxic dose of the pharmaceutical substance. We investigated the indicators characterizing the state of platelet and coagulation hemostasis in the blood plasma, the content of the stable NO metabolites and the activity of nitrogen oxide synthase (NOS) in the liver homogenate, blood plasma and urine of rats. We found that sub-chronic succinamides introduction reduced the nitrite and nitrate anions concentration in the blood plasma (by 30-50 and 20-35% resp.), liver (by 16-19 and 14-18%) and urine (by 50-70 and 38-55%). These changes were essentially dependent on the reduction in the NOS activity (by 33%). The studied compounds showed a 1.5 fold increase in the coagulation potential of the blood plasma and cause a 20% boost in the aggregation of thrombocytes. Analysis of the pair correlation coefficients showed positive association of the changes in indicators of the NO metabolism and hemostasis. The obtained results suggest that the registered manifestation of the pro-coagulation and thrombogenic action of succinamides applied in the sub-toxic doses is partially determined by a drop of the vasoactive NO pool that in turn, occurs due to a decline of the NOS activity.

Keywords: nitric oxide; hemostasis; amides of succinic acid.


  1. Targher G, Chonchol M, Zoppini G, Franchini M. Hemostasis disorders in type 1 diabetes mellitus. Semin Thromb Hemost. 2011;37(1):58-65. CrossRef PubMed
  3. Syropyatov BYa, Kolotova NV, Dolzhenko AV. Effect of derivatives of succinic and maleic acids on blood coagulation. Probl Biol, Med & Pharmaceut Chem. 2012;(5):31-6. [Russian].
  5. Ercan M, Firtina S, Konukoglu D. Comparison of plasma viscosity as a marker of endothelial dysfunction with nitric oxide and asymmetric dimethylarginine in subjects with dyslipidemia. Clin Hemorheol Microcirc 2014;57(4):315-23.
  7. Gorbenko NI. Pathogenic basis of succinic acid derivative - phensuccinal efficacy in therapy of diabetes mellitus and its complications (experimental study) [dissertation]. Kharkiv: V. Danilevsky Institute of Endocrine Pathology Problems at AMS of Ukraine; 2004. [Ukrainian].
  9. Palagina IA, Kudria MY, Ustenko NV. Assessment criteria of safety and risk of drugs with anti-diabetic and estrogenoid activeness [abstract]. Toxicology Letters. 2008;180 Suppl 1:S241.
  11. Mayer B, ed. Nitric oxide. New York: Springer Science & Business Media; 2012.
  13. Wu G, Meininger CJ. Nitric oxide and vascular insulin resistance. Biofactors. 2009;35:21-7. CrossRef PubMed
  15. Li H, Horke S, Forstermann U. Vascular oxidative stress, nitric oxide and atherosclerosis. Atherosclerosis. 2014 Nov;237(1):208-19.
  17. Bloomgarden ZT. Cardiovascular diseases in diabetes. Diabetes Care. 2010;33:49-54. CrossRef PubMed
  19. Tabit CE, Chung WB, Hamburg NM. Endothelial dysfunction in diabetes mellitus: molecular mechanisms and chemical implications. Reviews in Endocrine and Metabolic Disorders. 2011;11:61-74. CrossRef PubMed PubMedCentral
  21. Kim JH, Bae HY, Kim SY. Clinical marker of platelet hyperreactivity in diabetes mellitus. Diabetes Metab J. 2013;37(6):423-28. CrossRef PubMed PubMedCentral
  23. Kravets EB. Diabetology: scale of problem, achievements and perspective directions. Bull of Siberian Medicine. 2005;(1):9-18. [Russian].
  25. Menshikov VV, editor. Laboratory methods of study in the clinics. Laboratory manual. Moscow: Medicine; 1987; p. 378. [Russian].
  27. Solodkov AP, Veremey IS, Osotchuk SS, Sherbinin IU, Dedun GV, Dubrovskaya AV. Photometric method of defining nitrites and nitrates in biological liquids (Manual): appr. by Ministry of Health Care of Belarus Rep. 19.03.01. Vitebsk: [w/o publ.]; 2001; p. 9. [Russian].
  29. Sumbaev VV, Yasinskaya IM. DDT effect on rat liver, lungs and brain nitric oxide synthase activity. Modern Probl Toxicol 2000;(3):3-7. [Russian].
  31. Gasparov VS, Gegtyar VG. Definition of protein by its linkage to Kumassi Diamond light-blue G-250 dye. Biochem. 1994;59(6):763-75. [Russian].
  33. Palagina IA, Kudrya MYa. State of thrombocyte-coagulation hemostasis in rats under influence of metabolites of succinic acid derivatives. Probl Endocrine Pathology 2013;(3):82-7. [Russian].
  35. Palagina IA, Lalymenko OS, Kudria MY. Influence of succinate-carrying compounds on the NO-synthase activeness and thrombocyte-coagulation hemostasis [abstract]. Ukr Biochem J. 2014;86(5 Suppl 2):S120. [Ukrainian].
  37. Laposata M, editor. Coagulation disorders: Diagnostic standards of care. New York: Demos Medical Publ.; 2010. 136 p.
  39. Jansson EA, Huang L, Malkey RA Mammalian functional nitrate reductase that regulates nitrite and nitric oxide homeostasis. Nat Chem Biol. 2008; 4(7):411-7. CrossRef PubMed
  41. Shumaev KB, Kosmachevskaya OV, Timoshin AA. Dinitrosyl iron complexes bind with hemoglobin as markers of oxidative stress. Methods Enzymol. 2008; 436: 445-61. CrossRef  
  42. Toledo JC Jr, Augusto O Connecting the chemical and biological properties of nitric oxide. Chem Res Toxicol. 2012; 25(5):975-89. CrossRef PubMed
  44. Horita S, Nakamura M, Shirai A, Yamazaki O, Satoh N, Suzuki M, et al. Regulatory roles of nitric oxide and angiotensin II on renal tubular transport. J World Nephrol. 2014;3(4):295-301. CrossRef PubMed PubMedCentral
  46. Kudria MY, Palagina IA, Mishenko TV, Ustenko NV, Pavlenko TA, Zhurakovskaya MV. Influence of phensuccinal and its metabolites on carbohydrate and energy metabolism at rats in the conditions of subchronic experiments. Probl Endocrine Pathology. 2012;(4):109-15. [Russian].

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