Українська Русский English

ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

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. 2018; 64(1): 82-90


Nephroprotective properties of ATP-sensitive potassium channels agonist flocalin

A.І. Gozhenko1, N.D. Fіlipets2, O.O. Filipets2, O.A. Gozhenko1

  1. State Enterprise «Ukrainian Research Institute of Transport Medicine», Odessa, Ukraine
  2. Higher State Educational Institution «Bukovinian State Medical University», Chernivtsi, Ukraine
DOI: https://doi.org/10.15407/fz64.01.082

Abstract

protection against ischemia and hypoxia, arousing an interest in search and study of the pharmacological activators of potassium current. Review is devoted to a generalized scientific literary data justifying a wide pharmacodynamical spectrum of flocalin – a potential drug from the class of KATP-channels activators with its features as a cardioprotector, myotropic spasmolytic, vasodilator and cerebroprotector. Results of own research showing the ability of flocalin to maintain homeostatic functions of kidneys under the conditions of water-salt loading are also represented. Taking into consideration cardiorenal continuum, pathogenetic connection between renal and cardiac pathology makes it possible to suggest an inhibitory influence of flocalin on the development of nephropathy. A prerequisite for a study of its renal effects is data concerning the mechanisms of correction the morphological, functional and biochemical pathological changes in myocardium by flocalin, which allows positioning this new activator of KATP-channels as a perspective cardioprotector and also may give rise to a new direction in nephroprotection.

Keywords: activator of ATP-sensitive potassium channels flocalin; pharmacodynamics; cardioprotection; nephroprotection.

References

  1. Yagupolskii LM, Petko KI, Tarasova YeV. Fluorinecontaining potassium chanels activators – fflokaline and it's analogs. J Organical and pharmaceutical chemistry. 2004;2(4):11-6. [Ukrainian].
  2.  
  3. Strutynskyi RB, Mokchort MA, Yagupolskii LM, Moybenko OO. Flokalin – new domestic cardioprotectors. Vestnik of Pharmacol and Pharmacy. 2010;3:44-6. [Ukrainian].
  4.  
  5. Moybenko OO, Strutynskyi RB, Yagupolskii LM, Mohort Ma. Creation and preparation of the new domestic cardioprotective drug – fluorine-containing activator of ATP-dependent potassium channels flokalin. Nauka innov. 2006;2(4):114-9. [Ukrainian].
  6.  
  7. Strutynskyi RB, Moybenko OO, Chebanov VA, Gorobets NYu. Modeling of production industrial process of the drug flocalin and search of its optimally effective dose for treatment of heart diseases. Nauka innov. 2013;9(1):55-3. [Ukrainian].
  8.  
  9. Cleland JG, Carubelli V, Castiello T, Yassin A, Pellicori P, Antony R. Renal dysfunction in acute and chronic heart failure: prevalence, incidence and prognosis. Heart Fail Rev. 2012;17(2):133-9. CrossRef PubMed
  10.  
  11. Testani JM, Cappola TP, McCauley BD, Chen J, Shen J, Shannon RP, et al. Impact of worsening renal function during the treatment of decompensated heart failure on changes in renal function during subsequent hospitalizations. Am Heart J. 2011;161(5):944-9. CrossRef PubMed PubMedCentral
  12.  
  13. Damman K, Valente MA, Voors AA, O'Connor CM, Van Veldhuisen DJ, Hillege HL. Renal impairment, worsening renal function, and outcome in patients with heart failure: an updated meta-analysis. Eur Heart J. 2014;35(7):455-9. CrossRef PubMed
  14.  
  15. Moybenko aa, Dosenko VE, Parkhomenko aN. Endogenous mechanisms of cardioprotection as the basis of pathogenetic therapy of heart disease. Kyiv: Scientific thought, 2008. [Ukrainian].
  16.  
  17. Mills KT, Chen J, Yang W, Appel LJ, Kusek JW, Alper A. et al. Sodium excretion and the risk of cardiovascular disease in patients with chronic kidney disease. JAMA. 2016;315(20):2200-10. CrossRef PubMed PubMedCentral
  18.  
  19. Tsuruya K, Eriguchi M. Cardiorenal syndrome in chronic kidney disease. Curr Opin Nephrol Hypertens. 2015;24(2):154-2. CrossRef PubMed
  20.  
  21. Voitychuk OI, Strutynskyi RB, Yagupolskii LM, Tinker A, Moibenko OO, Shuba YM. Sarcolemmal cardiac KATP channels as a target for the sardioprotective effects the fluorine-containing panacidil analog flocalin. Br J Pharmacol. 2011;162(3):701-1. CrossRef PubMed PubMedCentral
  22.  
  23. Strutyns'kyĭ RB. Cardioprotective effects of fluorinecontaining activator of adenosine triphosphate-dependent potassium channels flokalin. Fiziol Zh. 2009;55(4):83-90. [Ukrainian].
  24.  
  25. Moybenko OO, Strutynskyi RB, Yagupolskii LM. Organization of іndustrial rroduction of flokalin – new myotropic spasmolytic and cardioprotector. Nauka innov. 2009;5(1):80-4. [Ukrainian].
  26.  
  27. Strutyns'kyĭ RB. The vasodilation effects of flocalin, a fluorine-containing K(ATP) channel opener. Fiziol Zh. 2010;56(4):59-5. [Ukrainian].
  28.  
  29. Strutyns'kyĭ RB, Rovenets' RA, Neshcheret OP. Effect of a new activator of adenosine triphosphate-sensitive potassium channels flocalin on the glucose level in blood. Fiziol Zh. 2010;56(6):39-7. [Ukrainian].
  30.  
  31. Strutyns'kyĭ RB, Moĭbenko OO, Pyvovar SM, Dosenko VIe, Iahupol's'kyĭ LM. ATP-sensitive potassium channels and changes in their functional activity during streptozocin- induced diabetes mellitus. Fiziol Zh. 2003;49(6):22-30. [Ukrainian].
  32.  
  33. Strutynsk'kyĭ RB, Moĭbenko OO. Modeling of K+ATP channel activity in normotensive and hypertensive animals. Fiziol Zh. 2000;46(6):54-60. [Ukrainian].
  34.  
  35. Strutyns'kyĭ RB, Neshcheret OP, Tumanovs'ka LV, Rovenets' RA, Moĭbenko OO. Cardioprotective effects of flokalin in experiments in vivo: influence on hemodynamic and myocardial lesions in ischemia-reperfusion. Fiziol Zh. 2009;55(5):9-6. [Ukrainian].
  36.  
  37. Raymond R. Townsend RR, Taler SJ. Management of hypertension in chronic kidney disease. Nat. Rev. Nephrol. 2015;11:555-3.
  38.  
  39. Strutyns'kyĭ RB, Neshcheret OP, Tumanovs'ka LV, Rovenets' RA, Moĭbenko OO. Cardioprotective effects of flokalin in experiments in vivo: influence on hemodynamic and myocardial lesions in ischemia-reperfusion. Fiziol Zh. 2009;55(5):9-6. [Ukrainian].
  40.  
  41. Mokhort MA, Kutovyii IM. Protective effects of pharmacological preconditioning by imidazo[1,2-a] azepinium derivatives on rat heart function in vivoupon regional ischemia. Pharmacol Drug Toxicol. 2016;1:1-6. [Ukrainian].
  42.  
  43. Obi Y, Kim T, Kovesdy CP, Amin AN, Kalantar-Zadeh K. Current and Potential Therapeutic Strategies for Hemodynamic Cardiorenal Syndrome. Cardiorenal Med. 2016;6(2):83-98. CrossRef PubMed PubMedCentral
  44.  
  45. Schefold JC, Filippatos G, Hasenfuss G, Anker SD, Haehling S. Heart failure and kidney dysfunction: epidemiology, mechanisms and management. Nat Rev Nephrol. 2016;12:610-3. CrossRef PubMed
  46.  
  47. Kazory A. Ultrafiltration therapy for heart failure: valancing likely benefits against possible risks. Clin J Am Soc Nephrol. 2016;11(8):1463-1. CrossRef PubMed PubMedCentral
  48.  
  49. Gozhenko AI. Functional-metabolic continuum. J NAMS Ukraine. 2016;22(1):3-8. [Ukrainian].
  50.  
  51. Strutyns'kyĭ RB, Rovenets RA, Neshcheret OP, Tumanovska LV, Boĭchuk TM, Dzhuran BV, Moĭbenko OO. Effect of medical form of flocalin on the course of myocardial reperfusion injury. Fiziol Zh. 2011;57(1):55-65. [Ukrainian].
  52.  
  53. Voitychuk OI, Srutyns′kyi RB, Shuba YM. Effects of ATP-dependent potassium channel activator flocalin include sodium and calcium channels inhibition in cardiomyocytes. Biophysical J. 2011;100(3), suppl.1:433a.
  54.  
  55. Voitychuk OI, Strutynskyi RB, Moibenko OO, Shuba YM. Effects of fluorine-containing opener of ATP-sensitive potassium channels, pinacidil-derivative flocalin, on cardiac voltage-gated sodium and calcium channels. Naunyn-Schmiedeberg's archives of pharmacology. 2012;385 (11):1095-2. CrossRef PubMed
  56.  
  57. Kramer RE Angiotensin II-stimulated changes m calcium metabolism in cultured glomerulosa cells. Mol Cell Endocrinol. 1988;60(2-3):199-10.
  58.  
  59. Bakris GL, Weir MR, Secic M, Campbell B, Weis- McNulty A. Differential effects of calcium antagonist subclasses on markers of nephropathy progression. Kidney Int. 2004;65(6):1991-02. CrossRef PubMed
  60.  
  61. Zhang J, Cao H, Zhang Y, Zhang Y, Ma J, Wang J, Gao Y, Zhang X, Zhang F, Chu L. Nephroprotective effect of calcium channel blockers against toxicity of lead exposure in mice. Toxicol Lett. 2013;218(3):273-80. CrossRef PubMed
  62.  
  63. Huang RS, Cheng YM, Zeng XX, Kim S, Fu P. Renoprotective effect of the combination of renin-angiotensin system Inhibitor and calcium channel blocker in patients with hypertension and chronic kidney disease. Chin Med J (Engl). 2016;129(5):562-9. CrossRef PubMed PubMedCentral
  64.  
  65. Strutynsky RB, Rovenets RA, Moybenko AA. Mechanisms cardioprotective actions of domestic KaTF channel activator flokalin. Taurian Med Biol J. 2012;15(3, part 2):226-9. [Ukrainian].
  66.  
  67. Strutyns'kyĭ RB, Kotsiuruba AV, Rovenets' RA, Strutyns'ka NA, Iagupols'kyĭ IuL, Sagach VF, Moĭbenko OO. Biochemical mechanisms of the cardioprotective effect of the K(ATP) channels opener flocalin (medicinal form) in ischemia-reperfusion of myocardium. Fiziol Zh. 2013;59(4):16-7. [Ukrainian].
  68.  
  69. Gozhenko AI, Dolomatov SI, Badyin IYu, Nasibullin BA. Renal mechanisms of regulation of the nitrogen oxide cycle in white rats loaded with sodium nitrite. Nephrology. 2005;9(3):95-8. [Russian].
  70.  
  71. Gozhenko AI. Susla OB. Sydorenko OL. The effect of arginine glutamate and meldonium combination on chronic inflammation and the endothelial function in patients with cardiac valve calcification on the predialysis stage of chronic kidney disease. Buk Med Herald. 2012;16(3, part 2):83-8. [Ukrainian].
  72.  
  73. Davidson SM, Duchen MR. Endothelial mitochondria contributing to vascular function and descase. Circulat Res. 2007;100(8):1128-1. CrossRef PubMed
  74.  
  75. Strutyns'ka NA, Strutyns'kyĭ RB, Chorna SV, Semenykhina OM, Mys' LA, Moĭbenko OO, Sahach VF. New fluorine-containing openers of ATP-sensitive potassium channels flokalin and tioflokalin inhibit calcium-induced mitochondrial pore opening in rat hearts. Fiziol Zh. 2013;59(6):3-11. [Ukrainian].
  76.  
  77. Gozhenko AI. Energy supply of basic renal functions and processes in normal and renal damage: abstract dis. doct. med. sci: 14.00.16 «Pathological physiology». Kyiv, 1987. [Ukrainian].
  78.  
  79. Mochort MA, Seredinskaya NN, Kirichok LM. Cardiotoxic effects of doxorubicin and expediency of its pharmacological correction by dihydropyridinic line calcium antagonists and by guanidine line ATR-sensitive potassium canals activators. Pharmacol Drug Toxicol. 2010;4:35-4. [Ukrainian].
  80.  
  81. Saenko YuV, Shutov AM, Musina RKh. On the mechanism of toxic effect of doxorubicin on the kidneys. Nephrology. 2006;10(4):72-6. [Russian].
  82.  
  83. Akoudad S, Sedaghat S, Hofman A. Koudstaal PJ, van der Lugt A, Ikram MA, Vernooij MW. Kidney function and cerebral small vessel disease in the general population. Int J Stroke. 2015;10(4):603-8. CrossRef PubMed
  84.  
  85. Dong K, Huang X, Zhang Q, Yu Z, Ding J, Song H. A lower baseline glomerular filtration rate predicts high mortality and newly cerebrovascular accidents in acute ischemic stroke patients. Medicine (Baltimore). 2017;96(5):e5868.
  86.  
  87. Denysyuk OM. Neuroprotective effect of new guanidine derivatives in experimental brain ischemia: abstract dis. cand. med. sci: 14.03.05 «Pharmacology». Odessa, 2012. [Ukrainian].
  88.  
  89. Lymarenko ІV. The search of novel potential detrusorselective compounds among guanidine derivatives: abstract dis. cand. med. sci: 14.03.05 «Pharmacology». Kyiv, 2006. [Ukrainian].
  90.  
  91. Mochort MA, Pupisheva OV. Comparative spasmolytic activity of drotaverin, pinacidil and its fluorinated analog flocalin. Achievements Biol Med. 2011;1:4-7. [Ukrainian].
  92.  
  93. Mokhort NA, Samarskaya IV, Yagupolskіі LM. Comparative study of the effects of new fluorine-containing pinacidyl analogs on bladder contractile function and vessel tone. Experim Clin Pharmacol. 2007;7(4):32-4. [Russian].
  94.  
  95. Boichuk TM, Dzhuran BV, Yanchyi RI, Kogut VV. New pharmacological approaches in relaxing smooth muscles of ureter in case of urethropyeloscopy. Clin Experim Pathol. 2010;9(3):12-3. [Ukrainian].
  96.  
  97. Strutyns'kyĭ RB, Rovenets' RA, Strutyns'ka NA, Neshcheret OP, Moĭbenko OO. The influence of activation of the ATP-sensitive potassium channels by flocalin on the function of the cardiovascular system. Fiziol Zh. 2013;59(1):11-6. [Ukrainian].
  98.  
  99. Khmil NV, Gorbacheva OS, Strutinskiy RB, Korobeynikova MO, Belosludtseva NV, Murzaeva SV, Mironova G.D. A study of the effects of flocalin on respiration and potassium transport of rat-heart and liver mitochondria. Biophysics. 2016;61(5):888-2. [Russian].
  100.  
  101. Filipets ND. A research of the renal activity of a new fluorine- containing activator of ATP-sensitive K+channels. Buk Med Herald. 2012;16(1):144-7. [Ukrainian].
  102.  
  103. Filipets ND. Influence of different doses of potassium channels activator flocalin on the functional state of kidneys in case of volume increase of extracellular fluid. Clin Experim Pathol. 2012;11(1):154-7. [Ukrainian].
  104.  
  105. Filipets ND. Filipets OO. The state of homeostatic function of the kidneys after repeated activation of potassium channels with flocalin at salt load. J Medicines of Ukraine. 2012;1-2:66-9. [Ukrainian].
  106.  
  107. Filipets ND. The effect of ATP-sensitive potassium channels activator flocalin on acid-regulator function of kidneys under conditions of load with 0,45% solution of sodium chloride. Taurian Med Biol J. 2012;15(3, part 1):358-60. [Ukrainian].
  108.  

© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2020.