COMPARATIVE EVALUATION OF NEURORETINOPROTECTIVE ACTIVITY OF ADEMOLE AS MONOTHERAPY AND COMBINED WITH MEXIDOL (SEPARATE USAGE) IN COMPLEX THERAPY OF EYE TRANSITIONAL ISCHEMIA IN RATS BASED ON CHANGES OF METABOLIC PROCESSES IN RETINA
DOI:
https://doi.org/10.11603/1811-2471.2017.v0.i2.7521Keywords:
ademol, mexidol, ischemia-reperfusion of the eye, retina.Abstract
Introduction. The actual task of modern pharmacology is the development of drugs based on biologically active substances, which can become a platform for creating news drugs with neurocytoprotective activity in the therapy of ischemic lesions of the visual analyzer (ILVA).
The aim of the study – to examine the effect of a blocker of NMDA-receptor ademol on metabolic processes in the retina in acute postreperfusion period as possible intracellular mechanism of neuroretinoprotective action of the drug and evaluate its effectiveness in combination with mexidol in the complex therapy of (ILVA).
Materials and Methods. Therapeutic use of an ampoule 1.0 % ademol solution at conventionally effective dose of 2 mg/kg intraperitoneally, every 12 hours during the first day of acute post-reperfusion period (the application and further tightening of retrobulbar ligatures to a stop of blood flow in retinal vessels with an exposure time of 1 hour). In parallel, a combined separate sequential administration of ademol (2 mg/kg) and mexidol (100 mg/kg) was performed with an interval of 10 minutes in a similar scheme. The last injection was performed in 1 hour before the completion of the experiment and euthanasia of the animals.
Results. Ademol at a dose of 2 mg/kg, exhibits a complex corrective effect on impaired intracellular metabolic processes in the retina, which is manifested by the elimination of energy deficiency (preservation of the adenosine triphosphate acid pool in comparison with the control pathology at the level of 18.2 %), antioxidative effect (33.1 and 26.9 % decrease in the level of markers of peroxide oxidation of lipids and oxidative modification of proteins: malonic dialdehyde and carbonyl groups of proteins, respectively, with a simultaneous increase in the activity of glutathione peroxidase by 36.0 %, p<0.05) and a modulating effect on the exchange of nitrogen monoxide by reducing the level of stable metabolites of nitrogen monoxide by an average of 58.0 %. On the background of separate sequential application of ademol (2 mg/kg) and mexidol (100 mg/kg) as a part of the complex therapy of ischemia-reperfusion of the rat eye, significant potentiation and summation of positive metabolitotropic phenomena at the level of the test markers is noted.
Conclusions. The above-mentioned biochemical changes characterize the leading metabolitotropic intracellular (non-receptor) mechanisms of the neuroretinoprotective action of the drug. The obtained data justify the expediency of further preclinical evaluation of the effectiveness of ademol-mexidol combination in the complex therapy of ILVA and make it promising to create a combined pharmaceutical composition.
References
Chereshniuk I. L. Kharakterystyka neyroretynoprotektornykh vlastyvostey ademolu za morfolohichnymy zminamy sitkivky ta zorovoho nerva pry eksperymental'niy ishemiyi-reperfuziyi oka na tli aloksanovoho tsukrovoho diabetu / I. L. Chereshniuk, O. A. Khodakivskyi, H. V. Zahorii // Intehratyvna antropolohiya. – 2015. – № 2. – S. 51-55. [in Ukrainian].
Chereshniuk I. L. Efektyvnist' ademolu u postreperfuziynyy period total'noyi ishemiyi oka kriz' pryzmu zasad suchasnoyi neyroretynoprotektyvnoyi terapiyi / I. L. Chereshniuk // Visnyk Vinnyts'koho natsional'noho medychnoho universytetu. – 2015. – № 1 (19). – S. 14-20. [in Ukrainian].
Chereshniuk I. L. Osoblyvosti perebihu metabolichnykh protsesiv u sitkivtsi shchuriv v umovakh hostroyi ishemiyi-reperfuziyi oka (kharakterystyka modeli) ta otsinka retynoprotektornykh vlastyvostey meksydolu / I. L. Chereshniuk, H. V. Zahorii, O. A. Khodakivskyi // Bukovyns'kyy medychnyy visnyk. – 2015. – № 4 (19). – S. 193-197. [in Ukrainian].
Tserebrovaskulyarnye effekty blokatorov NMDA-retseptorov y meksydola na fone alloksanovoho sakharnoho dyabeta, a takzhe ykh vlyyanye na techenye metabolycheskykh protsessov v setchatke monhol'skykh peschanok v ostryy postperfuzyonnyy peryod / I. L. Chereshniuk, V. L. Povkh, H. V. Zahorii, O. A. Khodakivskyi // Vrach-aspyrant. – 2016. – № 1.2 (74). – S. 295-303. [in Russian].
Chereshniuk I. L. Neyroretynoprotektorni vlastyvosti meksydolu v umovakh perekhidnoyi ishemiyi oka / I. L. Chereshniuk, H. V. Zahorii, O. A. Khodakivskyi // Biomedical and Biosocial Anthropology. – 2015. – № 24. – S. 90-92. [in Ukrainian].
Dyrektyva Soveta ES o sblyzhenyy zakonov, postanovlenyy y admynystryrovanye polozhenyy hosudarstv ES po voprosam zashchyty zhyvotnykh, yspol'zuemykh dlya эksperymental'nykh y druhykh nauchnykh tseley (86/609/EES) // V kn.: Nadlezhashchaya proyzvodstvennaya praktyka lekarstvennykh sredstv // Pod red. N. A. Liapunova, V. A. Zahoryia, V. P. Heorhyevskoho, E. P. Bezuhloi . – K: "Moryon". – 1999. – S. 508-545. [in Russian].
Simone F. Biotechnology, animal health and animal welf are within the framework of European Unionlegislation / F. Simone, J. Serratosa // Rev. Sci. Tech. Оіе. – 2005. – Vol. 24, № 1. – Р. 89-99.
Minhas G. Preclinical models to investigate retinal ischemia: advances and drawbacks / G. Minhas, R. Morishita, A. Anand // Front Neurol. – 2012. – Vol. 3. – P. 75.
Khodakivskyi O. A. Patohenetychne obgruntuvannya dotsil'nosti vykorystannya novykh pokhidnykh adamantanu pry eksperymental'niy terapiyi hostroyi ishemiyi holovnoho mozku ta miokarda (eksperymental'ne doslidzhennya): avtoref. dys. d. med. n.: spets. 14.03.05 – farmakolohiya / O. A. Khodakivskyi. – Odesa, 2014. – 24 s.
Prokhorova M. Y. Sovremennye metody byokhymycheskykh yssledovanyy (lypydnyy y enerhetycheskyy obmen) / M. Y. Prokhorova. – Lenynhrad: Yzd-vo Lenynhradskoho unyversyteta, 1982. – 272 s. [in Russian].
Kochetov H. A. Praktycheskoe rukovodstvo po эnzymolohyy / H. A. Kochetov. – M.: Vysshaya shkola, 1980. – 272 s. [in Russian].
Vladymyrov Yu. V. Perekysnoe okyslenye lypydov v byolohycheskykh membranakh / Yu. V. Vladymyrov, A. Y. Archakov. – M.: Nauka, 1972. – 252 s. [in Russian].
Zaichko N. V. Okyslyuval'na modyfikatsiya bilkiv syrovatky krovi yak marker aktyvnosti revmatoyidnoho artrytu ta yiyi zminy pid vplyvom farmakoterapiyi amizonom, indometatsynom, nimesulidom / N. V. Zaichko // Visnyk Vinnyts'koho natsional'noho medychnoho universytetu. – 2003. – № 7. – S. 664-666. [in Ukrainian].
Korenman Y. M. Metody opredelenyya orhanycheskykh soedynenyy / Y. M. Korenman. – M.: Khymyya, 1975. – 360 s. [in Russian].
Vlasova S. N. Aktyvnost' hlutatyon-zavysymykh fermentov эrytrotsytov pry khronycheskykh zabolevanyyakh pecheny u detey / S. N. Vlasova, E. Y. Shabunyna, Y. A. Perslehyna // Lab. delo. – 1990. – № 8. – S. 19-22. [in Russian].
