The antiproteinuric effect of ATP-sensitive potassium channel activator flocalin on the models of experimental nephropathies
N.D. Filipets1, A.I. Gozhenko2, O.O. Filipets1, O.A. Gozhenko2, V.M. Sirman2
- Higher State Educational Establishment «Bukovinian State Medical University», Chernivtsi, Ukraine
- State enterprise «Ukrainian Research Institute for Medicine of Transport of Ministry of Health of Ukraine», Odessa, Ukraine
In experiments on laboratory non-linear white rats with sublimate nephropathy (mercury dichloride, 5 mg/
kg subcutaneously) and hypoxic histohemic nephropathy (HHHN; sodium nitrite, 50 mg/kg subcutaneously
and 2,4-dinitrophenol, 3 mg/kg intraperitoneally) the effect of ATP-sensitive potassium (KATP) channels
activation induced by flocalin (5 mg/kg intragastric administration, for 7 days) on kidney protein excretion
was studied. Flocalin use causes a decrease in standardized by glomerular filtration rate proteinuria:
by 4.5 times and 1.2 times in rats with both acute and chronic sublimate nephropathy; and by 1.6 and 2.1
times, simultaneously, under the conditions of hypoxic injury of nephrocytes. Antiproteinuric effect of flocalin
during both acute and chronic periods of nephropathy was accompanied by an increase in enzymatic
activity of alkaline phosphatase (by 18.1 % and 49.9 % – in rats with sublimate nephropathy; by 18.1 %
and 4 % – in rats with HHHN) and succinate dehydrogenase (by 36.3 % and 56. 7% in rats with sublimate
nephropathy; reaches control level in rats with acute НHHN and increases by 71.2 % in rats with chronic
НHHN) in kidney cortex. Conclusion was made about the nephroprotective effect of KATP-channels activation
induced by flocalin predominantly in the proximal part of nephrons.
KATP-channels activator flocalin; experimental nephropathy
- Noma A. ATP-regulated K+ channels in cardiac muscle. Nature. 1983;305(5930):147-48.
- Sikka P, Kapoor S, Bindra VK, Saini M, Saxena KK. Iptakalim: A novel multi-utility potassium channel opener. J Pharmacol Pharmacother. 2012;3(1):12-4.
- Afzal MZ, Reiter M, Gastonguay C, McGivern JV, Guan X, Ge ZD, Mack DL, Childers MK, Ebert AD, Strande JL. Nicorandil, a nitric oxide donor and ATP-sensitive potassium channel opener, protects against dystrophindeficient cardiomyopathy. J Cardiovasc Pharmacol Ther. 2016;21(6):549-62.
- Zhang X, Zhang X, Xiong Y, Xu C, Liu X, Lin J, Mu G, Xu S,Liu W. Sarcolemmal ATP-sensitive potassium channel protects cardiac myocytes against lipopolysaccharideinduced apoptosis. Int J Mol Med. 2016;38(3):758-66.
- Pyvovar SN, Korzhov VI, Strutinskii RB, Yagupolskii LM, Moibenko AA. The influence of the fluor-containing mitochondrial K ATP channels openers on the oxidative phosphorilation. Fiziol Zh. 2006;52(3):25-3. [Ukrainian].
- 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. Sci Innov. 2013;9(1):55-3. [Ukrainian].
- Gozhenko AI. Functional-and-metabolic sontinuum. J NAMS of Ukraine. 2016;22(1):3-8. [Ukrainian].
- Castrop H, Höcherl K, Kurtz A, Schweda F, Todorov V, Wagner C. Physiology of kidney renin. Physiol Rev. 2010;90:607-74.
- Humphries ESA, Dart C. Neuronal and cardiovascular potassium channels as therapeutic drug targets. J Biomol Screen. 2015;20(9):1055-73.
- Moybenko OO, Strutynskyi RB, Yagupolskii LM, Mohort MA. Creation and preparation of the new domestic cardioprotective drug – fluorine containing activator of ATR dependent potassium channel flokalin to put into operation. Sci Innov. 2006;2(4):77-2. [Ukrainian].
- Gozhenko AI, Kravchuk AV, Nikitenko OP, Moskolenko OM, Sirman VM. Renal functional reserve. Odessa: Fenix; 2015. [Ukrainian].
- Pak LB, Dubikov AI, Kabanceva TA, Vasilyuk AA, Grigoryan OM. Apoptosis and nephropathies. Nephrology. 2013;17(4): 36-3. [Russian].
- Gozhenko AI, Filipets ND. The functional state of kidneys after adenosine triphosphate sensitive potassium channels activation in experimental acute hypoxia. Fiziol Zh. 2014;60(4):22-9. [Ukrainian].
- Mahalyas VM, Myhyeyev AO, Rohovyy YuYe. Modern methods experimental and clinical studies of the central research laboratory BSMA. Chernivtsi: BSMA; 2001. [Ukrainian].
- Filipets ND, Gozhenko AI. Comparative assessment of nephroprotective properties of potassium and calcium channel modulators in experimental renal injury. Eksp Klin Farmakol. 2014;77(1):10-2. [Russian].
- Strutynskyi RB, Kotsuruba AV, Rovenets RA, Strutynska NA, Yagupolskii YL, Sagach VF, Moibenko OO. Biochemical mechanisms of cardioprotective action of the drug product Flocalin, ATP-sensitive K+ channel opener, in myocardial ischemia-reperfusion. Int J Phys Pathophys. 2014;5(3):231-44. [Ukrainian].