Fabomotizole as means of pharmacological correction of preand postnatal disturbances induced by peat smoke pollution, tobacco smoke, alcohol, hyperglycemia and cyclophophamide in the development of offspring of rats


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Abstract

Introduction. Influence of environmental hazards on pregnant women or development of pregnancy in presence of pathogenic pathway may lead to miscarriage, teratogenic effects and/or significant abnormalities in physical development, cognitive and behavioral state observed in offspring. Prevention and correction ofpre- and postnatal disturbances is the problem of high priority in modern pharmacology. The aim ofthe study. Influence of fabomotizole on pre- and postnatal abnormalities in the development of rat offspring exposed to peat smoke pollution, passive tobacco smoking, ethanol intake, gestational diabetes and cyclophosphamide-induces teratogenesis in compliant experimental models was studied. Methods. Fabomotizole was administered orally during pregnancy or before sampling of biomaterial in the dose range of 1 to 100 mg/kg. The level of DNA damage in placenta and fetus cells was assessed at the 13th day ofpregnancy, parameters of embryonic development were observed on the 20th day of pregnancy, the unconditional reflexes formation and muscle tone were evaluated at 5th day of postnatal life and the cognitive functions of the same offspring were measured at the age of 2-3 months. Results. Fabomotiz.ole in the range of therapeutic doses demonstrated the ability to reduce and/or fully eliminate DNA-damage in embryonic tissues, decrease the number of fetuses with external abnormalities, malformations of internal organs and skeletal system and corrected the disturbances in sensory-motor activity, behavior and cognitive functions resulted from negative impact of several factors. Conclusions. Protective action of fabomotizole can be connected with antimutagenic, antioxidative and neuroprotective properties due to its interaction with sigma-1 and MT1 receptors.

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A. S Solomina

Research Zakusov Institute of Pharmacology

Email: solomina@academpharm.ru

O. V Shreder

Research Zakusov Institute of Pharmacology

E. D Mokrova

Research Zakusov Institute of Pharmacology

V. V Zabrodina

Research Zakusov Institute of Pharmacology

D. M Gorbatova

Research Zakusov Institute of Pharmacology

L. G Kolik

Research Zakusov Institute of Pharmacology

A. D Durnev

Research Zakusov Institute of Pharmacology

References

  1. Шредер О.В., Шредер Е.Д., Дурнев А.Д., Середенин С.Б., Сопряженность генотоксических и тератогенных эффектов, вызываемых циклофосфамидом, и их модификация афобазолом. Гигиена и санитария. 2011; 5: 64-8
  2. Giavini E., Menegola E., Biomarkers of tera-togenesis: Suggestions from animal studies. Reproductive Toxicology 2012; 34 (2): 180-5. https://doi.org/10.1016/j.reprotox.2012.05.003
  3. Ferguson L.R., Ford J.H., Overlap between mutagens and teratogens. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 1997; 396 (1-2): 1-8. https://doi.org/10.1016/s0027-5107(97)00172-3
  4. Гончарова В., Жанатаев А., Чайка З., Дурнев А., Богдан Н., Луценко Н., Морозова К., Лунина С., Доброхотова Ю., Макаров. Анализ показателей генотоксичности при невынашивании беременности. Врач. 2016; 3: 21-4. [Goncharova V, Zhanataev A., Chaika Z., Durnev A., Bogdan N., Lutsenko N., Morozova K., Lunina S., Dobrokhotova Yu., Makarov O Genotoxicity analysis in miscarriage. Vrach. 2016; 3: 21-4 (in Russian)]
  5. Дурнев А.Д., Жанатаев А.К., Шредер О.В., Середенин С.Б. Антимутагенные и антитератогенные свойства афобазола. Экспериментальная и клиническая фармакологи. 2009; 72 (1): 46-51. [Durnev A.D., Zhanataev A.K., Shreder O.V, Seredenin S.B. Antimutagenic and antiteratogenic properties of afobazole Eksperimental'naya i Klinicheskaya Farma-kologiya. 2009; 72 (1): 46-51 (in Russian)]
  6. Беккер Р.А., Быков Ю.В. Афобазол (фабомотизол): анксиолитик, и не только (израильско-россйский взгляд на проблему). Психиатрия и психофармакотерапия. 2017; 19 (4): 12-21. [Bekker R.A., Bykov Yu.V. Afobazole (fabo-motizole): is it only an anxiolytic? An Israeli-Russian view of the problem. Psihiatrija i psihofarmakoterapija. 2017; 19 (4): 12-21 (in Russian)]
  7. Дурнев А.Д., Меркулов В.А., Жанатаев А.К., Никитина В.А., Воронина Е.С., Середенин С.Б. Методические рекомендации по оценке ДНК-повреждений методом щелочного гель-электрофореза отдельных клеток в фармакологических исследованиях. Руководство по проведению доклинических исследований лекарственных средств. М.: Гриф и К, 2012; 944.
  8. Дыбан А.П., Баранов В.С., Акимова И.М. Основные методические подходы к тестированию тератогенной активности химических веществ. Архив анатомии, гистологии и эмбриологии. 1970; 59 (10): 89. [Dyban A.P., Baranov VS., Akimova I.M. Osnovnye metodicheskie podhody k testirovaniju teratogennoj aktivnosti himich-eskih veshhestv. Arhiv anatomii, gistologii i jembriologii. 1970; 59 (10): 89 (in Russian)]
  9. Дурнев А.Д., Смольникова Н.М., Скосырева А.М., Немова Е.П., Соломина А.С., Шредер О.В., Гуськова Т.А., Верстакова О.Л., Сюбаев РД. Методические рекомендации по изучению репродуктивной токсичности лекарственных средств. Руководство по проведению доклинических исследований лекарственных средств. М.: Гриф и К, 2012; 944. [Durnev A.D., Smol'nikova N.M., Skosyreva A.M., Nemova E.P, Solomina A.S., Shreder O.V, Gus'kova T.A., Verstakova O.L., Sjubaev R.D. Metodicheskie rekomendacii po izucheniju reproduktivnoj toksichnosti lekarst-vennyh sredstv. Rukovodstvo po provedeniju doklinicheskih issledovanij lekarstvennyh sredstv. M.: Grif i K, 2012; 944 (in Russian)]
  10. Соломина А.С., Шредер Е.Д., Колик Л.Г, Дурнев А.Д. Исследование влияния фабомотизола на поведенческие нарушения у потомства крыс, подвергнутых действию табачного дыма или этанола. Фармакокинетика и фармакодинамика. 2018; 2: 3-15. [Solomina A.S., Shreder E.D., Kolik L.G., Durnev A.D. Study of fabomotizole effect on the behavioral disorders in rat offspring exposed to tobacco smoke and ethanol. Farmakokinetika i farmakodinamika. 2018; 2: 3-15 (in Russian)]
  11. Шредер О.В., Смольникова Н.М., Дурнев А.Д., Середенин С.Б. Влияние афобазола на тератогенные эффекты циклофосфамида у крыс. Бюллетень экспериментальной биологии и медицины. 2008; 145 (4): 414-7. [Shreder O.V, Smol'nikova N.M., Durnev A.D., Seredenin S.B. Effect of afobazole on teratogenic activity of cyclophosphamide in rats. Bulletin of Experimental Biology and Medicine. 2008; 145 (4): 414-7 (in Russian)]
  12. Соломина А.С., Жуков В.Н., Дурнев А.Д., Середенин С.Б. Влияние афобазола на эмбриональное развитие потомства у крыс, подвергнутых воздействию табачного дыма. Токсикологический вестник. 2011; 1: 17-21. [Solomina A.S., Zhukov V.N., Durnev A.D., Seredenin S.B. Impact of Afobasol on the embryonal development of the posterity of rats exposed to tobacco smoke Toksikolog-icheskij vestnik. 2011; 1: 17-21 (in Russian)]
  13. Горбатова Д.М., Немова Е.П., Соломина А.С., Дурнев А.Д., Середенин С.Б. Пренатальные эффекты продуктов сгорания торфа и их коррекция афобазолом у потомства крыс. Бюллетень экспериментальной биологии и медицины. 2014; 158 (11): 604-8. [Gorbatova D.M., Nemova E.P, Solomina A.S., Durnev A.D., Seredenin S.B. Prenatal Effects of Peat Combustion Products and Afobazole Correction Thereof in the Rat Progeny Bulletin of Experimental Biology and Medicine. 2015; 158 (5): 654-8 (in Russian)]
  14. Шредер Е.Д., Шредер О.В., Забродина B.В., Дурнев А.Д., Середенин С.Б. Влияние афобазола на нейротоксические и генотоксические эффекты в модели пренатальной алкоголизации крыс. Бюллетень экспериментальной биологии и медицины. 2014; 157 (4): 492-5. [Shreder E.D., Shreder O.V, Zabrodina V.V., Durnev A.D., Seredenin S.B. Afobazole Modifies the Neurotoxic and Genotoxic Effects in Rat Prenatal Alcoholization ModelBulletin of Experimental Biology and Medicine. 2014; 157 (4): 492-5 (in Russian)]
  15. Забродина В.В., Шредер О.В., Шредер Е.Д., Дурнев А.Д. Влияние «афобазола» и бетаина на нарушения когнитивных способностей у потомства крыс со стрептозотоциновым диабетом и их связь с повреждениями ДНК. Бюллетень экспериментальной биологии и медицины. 2016; 161 (3): 335-42. [Zabrodina V.V., Shreder O.V, Shreder E.D., Durnev A.D. Effect of Afobazole and Betaine on Cognitive Disorders in the Offspring of Rats with Streptozotocin-Induced Diabetes and Their Relationship with DNA Damage Bulletin of Experimental Biology and Medicine. 2016; 161 (3): 359-66 (in Russian)]
  16. Руководство по проведению доклинических исследований лекарственных средств. М.: Гриф и К, 2012; 944. [Rukovodstvo po provedeniju doklinicheskih issledovanij lekarstvennyh sredstv. M.: Grif i K, 2012; 944 (in Russian)]
  17. Murata M., Suzuki T., Midorikawa K., Oikawa S., Kawanishi S. Oxidative DNA damage induced by a hydroperoxide derivative of cyclophosphamide. Free Radical Biology and Medicine. 2004; 37 (6): 793-802. https://doi. org/10.1016/j.freeradbiomed.2004.05.009
  18. Harrouk W, Codrington A., Vinson R., Robaire B., Hales B. F. Paternal exposure to cyclophosphamide induces DNA damage and alters the expression of DNA repair genes in the rat preimplantation embryo. Mutation Research/DNA Repair. 2000; 461 (3): 229-41. https://doi.org/10.1016/s0921-8777(00)00063-7
  19. Середенин С.Б., Воронин М.В. Нейрорецепторные механизмы действия афобазола. Экспериментальная и клиническая фармакология. 2009; 72 (1): 3-11. [Seredenin S.B., Voronin M.V Neuroreceptor mechanisms involved in the action of afobazole. Jeksperimental'naja i klinich-eskaja farmakologija. 2009; 72 (1): 3-11 (in Russian)]
  20. Reite R.J., Rosales-Corral S., Tan D.X., Jou M.J., Galano A., Xu B. Melatonin as a mitochondria-targeted antioxidant: one of evolution's best ideas. Cell Mol Life Sci. 2017; 74 (21): 3863-81. https://doi. org/10.1007/s00018-017-2609-7
  21. Ramis M.R., Esteban S., Miralles A., Tan D.X., Reiter R.J. Protective Effects of melatonin and mitochondria-targeted antioxidants against oxidative stress: a review. Curr Med Chem. 2015; 22 (22): 2690-711. https://doi. org/10.2174/0929867322666150619104143
  22. Pedreanez A., Rincon J., Romero M., Viera N., Mosquera J. Melatonin decreases apoptosis and expression of apoptosis-associated proteins in acute puromycin aminonucleoside nephrosis. Nephrol Dial Transplant. 2004: 19 (5): 1098-105. https:// doi.org/10.1093/ndt/gfh068
  23. Chen S., Wu K., Knox R. Structure-function studies of DT-diaphorase (NQO1) and NRH: quinone oxidoreductase (NQO2). Free Radic Biol Med. 2000; 29 (3-4): 276-84. https://doi.org/10.1016/s0891-5849(00)00308-7
  24. Goguadze N., Zhuravliova E., Morin D., Mikeladze D., Maurice T. Sigma-1 receptor agonists induce oxidative stress in mitochondria and enhance complex I activity in physiological condition but protect against pathological oxidative stress. Neurotox Res. 2019; 35 (1): 1-18. https://doi. org/10.1007/s12640-017-9838-2
  25. Meunier J., Hayashi T. Sigma-1 receptors regulate Bcl-2 expression by reactive oxygen species-dependent transcriptional regulation of nuclear factor KB. J. Pharmacol. Exp. Ther. 2010; 332: 388-97. https://doi. org/10.1124/jpet.109.160960
  26. Hyrsky Luoto A., Pulli I., Tornqvist K., HuuHo T, Korhonen L., Lindholm D. Sigma-1 receptor agonist PRE084 is protective against mutant huntingtin-induced cell degeneration: involvement of calpastatin and the NF-kB pathway Cell Death Dis. 2013; 4: 646. https://doi.org/10.1038/cddis.2013.170
  27. Cuevas J., Behensky A., Deng W, Katnik C.J. Afobazole modulates neuronal response to ischemia and acidosis via activation of sigma-1 receptors. Pharmacol Exp Ther. 2011; 1 (152-160): 339. https://doi. org/10.1124/jpet.111183774.
  28. Behensky A.A., Shuster A.M., Seredenin S.B., Petrov A.V, Cuevas J. Afobazole activation of o-1 receptors modulates neuronal responses to amyloid-β25-35. J. Pharmacol. Exp. Ther. 2013; 347 (2): 468-77. https://doi. org/10.1124/jpet.113208330.
  29. Behensky A.A., Yasny I.E., Schuster A.M., Seredenin S.B., Petrov A.V, Cuevas J. Stimulation of sigma receptors with afobazole blocks ctivation of microglia and reduces toxicity caused by amyloid-β25-35. J. Pharmacol. Exp. Ther. 2013; 347 (2): 458-67. https://doi.org/10.1124/jpet.113.208348
  30. Wu Z., Li L., Zheng L.T., Xu Z., Guo L., Zhen X. Allosteric modulation of sigma-1 receptors by SKF83959 inhibits microglia-mediated inflammation. J. Neurochem. 2015; 134 (5): 904-14. https://doi.org/10.1111/jnc.13182

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