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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">phkinetica</journal-id><journal-title-group><journal-title xml:lang="ru">Фармакокинетика и Фармакодинамика</journal-title><trans-title-group xml:lang="en"><trans-title>Pharmacokinetics and Pharmacodynamics</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2587-7836</issn><issn pub-type="epub">2686-8830</issn><publisher><publisher-name>ООО «Издательство ОКИ»</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.24411/2587-7836-2018-10028</article-id><article-id custom-type="elpub" pub-id-type="custom">phkinetica-74</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ДОКЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯ ФАРМАКОДИНАМИКИ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>PRECLINICAL PHARMACODYNAMICS STUDIES</subject></subj-group></article-categories><title-group><article-title>Цитопротекторные свойства дипептидных миметиков фактора роста нервов и мозгового нейротрофического фактора, ГК-2 и ГСБ-106, в модели окислительного стресса у инфузорий</article-title><trans-title-group xml:lang="en"><trans-title>Cytoprotective properties of the nerve growth factor and brain derived neurotrophic factor dipeptidic mimetics, GK-2 AND GSB-106, in the model of oxidative stress in paramecium caudatum</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Карпухина</surname><given-names>Ольга Вячеславовна</given-names></name><name name-style="western" xml:lang="en"><surname>Karpukhina</surname><given-names>O. V.</given-names></name></name-alternatives><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Иноземцев</surname><given-names>Анатолий Николаевич</given-names></name><name name-style="western" xml:lang="en"><surname>Inozemtsev</surname><given-names>A. N.</given-names></name></name-alternatives><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Гумаргалиева</surname><given-names>Клара Зенноновна</given-names></name><name name-style="western" xml:lang="en"><surname>Gumargalieva</surname><given-names>K. Z.</given-names></name></name-alternatives><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Поварнина</surname><given-names>Полина Юрьевна</given-names></name><name name-style="western" xml:lang="en"><surname>Povarnina</surname><given-names>P. Yu.</given-names></name></name-alternatives><email xlink:type="simple">povarnina@gmail.com</email><xref ref-type="aff" rid="aff-3"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Гудашева</surname><given-names>Татьяна Александровна</given-names></name><name name-style="western" xml:lang="en"><surname>Gudasheva</surname><given-names>T. A.</given-names></name></name-alternatives><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-4"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>МГУ им. М. В. Ломоносова</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Lomonosov Moscow State University</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>Институт химической физики им. Н.Н. Семёнова РАН</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Semenov Institute of Chemical Physics of Russian Academy of Sciences</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru"><institution>ФГБНУ «Научно-исследовательский институт фармакологии имени В.В. Закусова»</institution><country>Россия</country></aff><aff xml:lang="en"><institution>FSBI «Zakusov Institute of Pharmacology»</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-4"><aff xml:lang="ru"><institution>ФГБНУ «НИИ фармакологии имени В.В. Закусова»</institution><country>Россия</country></aff><aff xml:lang="en"><institution>FSBI «Zakusov Institute of Pharmacology»</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2018</year></pub-date><pub-date pub-type="epub"><day>06</day><month>11</month><year>2018</year></pub-date><volume>0</volume><issue>4</issue><fpage>37</fpage><lpage>41</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Карпухина О.В., Иноземцев А.Н., Гумаргалиева К.З., Поварнина П.Ю., Гудашева Т.А., 2018</copyright-statement><copyright-year>2018</copyright-year><copyright-holder xml:lang="ru">Карпухина О.В., Иноземцев А.Н., Гумаргалиева К.З., Поварнина П.Ю., Гудашева Т.А.</copyright-holder><copyright-holder xml:lang="en">Karpukhina O.V., Inozemtsev A.N., Gumargalieva K.Z., Povarnina P.Y., Gudasheva T.A.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.pharmacokinetica.ru/jour/article/view/74">https://www.pharmacokinetica.ru/jour/article/view/74</self-uri><abstract/><trans-abstract xml:lang="en"><p>Resume. Actuality. Dimeric dipeptide mimics of the nerve growth factor ( NGF) and brain derived neurotrophic factor (BDNF), respectively GK-2 and GSB-106, were created in the V.V. Zakusov Institute of pharmacology. The similarity of GK-2 and GSB-106 to the corresponding full-sized neurotrophins by the mechanism of action and pharmacological properties, including pronounced neuroprotective activity in vitro and in vivo, has been established. The purpose of this study was to obtain additional data on the cytoprotective properties of GK-2 and GSB-106 using Paramecium caudatum. Methods. Oxidative stress in the Paramecium caudatum was induced by adding heavy metal salts (cadmium chloride, lead acetate, copper sulfate, zinc sulfate) to the medium at a final concentration of 10 |jM. GK-2 or GSB-106 in concentrations from 10-5 to 10-8 M was added into the medium with experimental cells 45 minutes before introducing the oxidative stress initiator. Results. Dipeptides GK-2 and GSB-106 in all studied concentrations protected cells from death. The maximum neuroprotective effect of the dipeptides showed in a concentration of 10-8 M, completely preventing the death of ciliates. Conclusion. GK-2 and GSB-106, at a concentration of 10-8M, completely protect against the death Paramecium caudatum under conditions of oxidative stress caused by heavy metal salts.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>фактор роста нервов</kwd><kwd>мозговой нейротрофический фактор</kwd><kwd>димерные дипептидные миметики</kwd><kwd>инфузории Paramecium caudatum</kwd><kwd>цитопротекция</kwd><kwd>окислительный стресс</kwd><kwd>вызванный солями тяжёлых металлов</kwd><kwd>nerve growth factor</kwd><kwd>brain-derived neurotrophic factor</kwd><kwd>dimeric dipeptide mimetics</kwd><kwd>Paramecium caudatum infusoria</kwd><kwd>cytoprotection</kwd><kwd>oxidative stress induced by heavy metal salts</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Работа была выполнена при поддержке РФФИ (проект № 18-015-00228).</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Allen SJ, Watson JJ, Shoemark DK, et al. GDNF, NGF and BDNF as therapeutic options for neurodegeneration. Pharmacol Ther. 2013;138(2):155–175. DOI: 10.1016/j.pharmthera.2013.01.004</mixed-citation><mixed-citation xml:lang="en">Allen SJ, Watson JJ, Shoemark DK, et al. GDNF, NGF and BDNF as therapeutic options for neurodegeneration. Pharmacol Ther. 2013;138(2):155–175. DOI: 10.1016/j.pharmthera.2013.01.004</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Aloe L, Rocco ML, Bianchi P, Manni L. Nerve growth factor: from the early discoveries to the potential clinical use. J Transl Med. 2012;10(1):239. DOI: 10.1186/1479-5876-10-239</mixed-citation><mixed-citation xml:lang="en">Aloe L, Rocco ML, Bianchi P, Manni L. Nerve growth factor: from the early discoveries to the potential clinical use. J Transl Med. 2012;10(1):239. DOI: 10.1186/1479-5876-10-239</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Dunkel P, Chai CL, Sperl gh B, et al. Clinical utility of neuroprotective agents in neurodegenerative diseases: current status of drug development for Alzheimer’s, Parkinson’s and Huntington’s diseases, and amyotrophic lateral sclerosis. ExpertOpinInvestigDrugs. 2012;21(9):1267–1308. DOI: 10.1517/13543784.2012.703178</mixed-citation><mixed-citation xml:lang="en">Dunkel P, Chai CL, Sperl gh B, et al. Clinical utility of neuroprotective agents in neurodegenerative diseases: current status of drug development for Alzheimer’s, Parkinson’s and Huntington’s diseases, and amyotrophic lateral sclerosis. ExpertOpinInvestigDrugs. 2012;21(9):1267–1308. DOI: 10.1517/13543784.2012.703178</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Антипова Т.А., Гудашева Т.А., Середенин С.Б. Исследование invitro нейропротективных свойств нового оригинального миметика фактора роста нервов ГК-2 // Бюллетень экспериментальной биологии и медицины. – 2010. – Т. 150. – № 11. – С.5 37-540. [Antipova TA, Gudasheva TA, Seredenin SB. In vitro study of neuroprotective properties of GK-2, a new original nerve growth factor mimetic. Bulleten experimentalnoy biologii i medicini. 2011;150(5):607–9. (in Russ).].</mixed-citation><mixed-citation xml:lang="en">Антипова Т.А., Гудашева Т.А., Середенин С.Б. Исследование invitro нейропротективных свойств нового оригинального миметика фактора роста нервов ГК-2 // Бюллетень экспериментальной биологии и медицины. – 2010. – Т. 150. – № 11. – С.5 37-540. [Antipova TA, Gudasheva TA, Seredenin SB. In vitro study of neuroprotective properties of GK-2, a new original nerve growth factor mimetic. Bulleten experimentalnoy biologii i medicini. 2011;150(5):607–9. (in Russ).].</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Гудашева Т.А., Тарасюк А.В., Помогайбо СВ и др. Дизайн и синтез дипептидных миметиков мозгового нейротрофического фактора // Биоорганическая Химия. – 2012. – Т. 38. – № 3. – С. 280–290. [Gudasheva TA, Tarasyuk AV., Pomogaybo SV, et al. Design and synthesis of dipeptide mimetics of brain-derived neurotrophic factor. Bioorganicheskaya chimiya. 2012;38(3):280–90. (In Russ).]</mixed-citation><mixed-citation xml:lang="en">Гудашева Т.А., Тарасюк А.В., Помогайбо СВ и др. Дизайн и синтез дипептидных миметиков мозгового нейротрофического фактора // Биоорганическая Химия. – 2012. – Т. 38. – № 3. – С. 280–290. [Gudasheva TA, Tarasyuk AV., Pomogaybo SV, et al. Design and synthesis of dipeptide mimetics of brain-derived neurotrophic factor. Bioorganicheskaya chimiya. 2012;38(3):280–90. (In Russ).]</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Gudasheva TA, Povarnina PY, Antipova TA, et al. Dimeric dipeptide mimetics of the nerve growth factor Loop 4 and Loop 1 activate TRKA with different patterns of intracellular signal transduction. J Biomed Sci. 2015;22(5):106. DOI: 10.1186/s12929-015-0198-z</mixed-citation><mixed-citation xml:lang="en">Gudasheva TA, Povarnina PY, Antipova TA, et al. Dimeric dipeptide mimetics of the nerve growth factor Loop 4 and Loop 1 activate TRKA with different patterns of intracellular signal transduction. J Biomed Sci. 2015;22(5):106. DOI: 10.1186/s12929-015-0198-z</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Gudasheva TA, Povarnina P, Logvinov IO, et al. Mimetics of brainderived neurotrophic factor loops 1 and 4 are active in a model of ischemic stroke in rats. Drug Des Devel Ther. 2016;10:3545–3553. DOI: 10.2147/DDDT.S118768</mixed-citation><mixed-citation xml:lang="en">Gudasheva TA, Povarnina P, Logvinov IO, et al. Mimetics of brainderived neurotrophic factor loops 1 and 4 are active in a model of ischemic stroke in rats. Drug Des Devel Ther. 2016;10:3545–3553. DOI: 10.2147/DDDT.S118768</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Povarnina P, Gudasheva TA, Seredenin SB. Dimeric dipeptide mimetics of NGF and BDNF are promising agents for post-stroke therapy. JBiomedSciEng. 2018;11(5):100–107. DOI: 10.4236/jbise.2018.115009</mixed-citation><mixed-citation xml:lang="en">Povarnina P, Gudasheva TA, Seredenin SB. Dimeric dipeptide mimetics of NGF and BDNF are promising agents for post-stroke therapy. JBiomedSciEng. 2018;11(5):100–107. DOI: 10.4236/jbise.2018.115009</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Середенин С.Б., Поварнина П.Ю., Гудашева Т.А. Экспериментальная оценка терапевтического окна нейропротективной активности препарата ГК-2, низкомолекулярного миметика фактора роста нервов // Журнал неврологии и психиатрии имени С.С. Корсакова. – 2018. – Т. 118. – № 7. – С. 49–53. DOI: 10.17116/jnevro20181187149 [Seredenin SB, Povarnina PY, Gudasheva TA, et al. An experimental evaluation of the therapeutic window of the neuroprotective activity of a low-molecular nerve growth factor mimetic GK-2. Zhurnal Nevrol i psikhiatrii im SS Korsakova. 2018;118(7):49. (in Russ).].</mixed-citation><mixed-citation xml:lang="en">Середенин С.Б., Поварнина П.Ю., Гудашева Т.А. Экспериментальная оценка терапевтического окна нейропротективной активности препарата ГК-2, низкомолекулярного миметика фактора роста нервов // Журнал неврологии и психиатрии имени С.С. Корсакова. – 2018. – Т. 118. – № 7. – С. 49–53. DOI: 10.17116/jnevro20181187149 [Seredenin SB, Povarnina PY, Gudasheva TA, et al. An experimental evaluation of the therapeutic window of the neuroprotective activity of a low-molecular nerve growth factor mimetic GK-2. Zhurnal Nevrol i psikhiatrii im SS Korsakova. 2018;118(7):49. (in Russ).].</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Karpukhina OV, Gumargalieva KZ, Inozemtsev AN. The effect of antioxidant compounds on oxidative stress in unicellular aquatic organisms. In: On the borders of physics, chemistry, biology, medicine and agriculture. Research and Development. Torun: Institute for Engineering of polymer materials and Dues. 2014:145–151.</mixed-citation><mixed-citation xml:lang="en">Karpukhina OV, Gumargalieva KZ, Inozemtsev AN. The effect of antioxidant compounds on oxidative stress in unicellular aquatic organisms. In: On the borders of physics, chemistry, biology, medicine and agriculture. Research and Development. Torun: Institute for Engineering of polymer materials and Dues. 2014:145–151.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Morgunov IG, Karpukhina OV, Kamzolova SV, et al. Investigation of the effect of biologically active threo-Ds-isocitric acid on oxidative stress in Paramecium caudatum. Prep Biochem Biotechnol. 2018;48(1):1–5. DOI: 10.1080/10826068.2017.1381622</mixed-citation><mixed-citation xml:lang="en">Morgunov IG, Karpukhina OV, Kamzolova SV, et al. Investigation of the effect of biologically active threo-Ds-isocitric acid on oxidative stress in Paramecium caudatum. Prep Biochem Biotechnol. 2018;48(1):1–5. DOI: 10.1080/10826068.2017.1381622</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Simmons SO, Fan C-Y, Yeoman K, et al. NRF2 Oxidative Stress Induced by Heavy Metals is Cell Type Dependent. Curr Chem Genomics. 2011;5:1–12. DOI: 10.2174/1875397301105010001</mixed-citation><mixed-citation xml:lang="en">Simmons SO, Fan C-Y, Yeoman K, et al. NRF2 Oxidative Stress Induced by Heavy Metals is Cell Type Dependent. Curr Chem Genomics. 2011;5:1–12. DOI: 10.2174/1875397301105010001</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Ercal N, Gurer-Orhan H, Aykin-Burns N. Toxic metals and oxidative stress part I: mechanisms involved in metal-induced oxidative damage. Curr Top Med Chem. 2001;1(6):529–539. DOI: 10.2174/1568026013394831</mixed-citation><mixed-citation xml:lang="en">Ercal N, Gurer-Orhan H, Aykin-Burns N. Toxic metals and oxidative stress part I: mechanisms involved in metal-induced oxidative damage. Curr Top Med Chem. 2001;1(6):529–539. DOI: 10.2174/1568026013394831</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Flora SJS, Mittal M, Mehta A. Heavy metal induced oxidative stress &amp; its possible reversal by chelation therapy. Indian J Med Res. 2008;128(4):501– 523. DOI: 10.1093/jexbot/53.366.1</mixed-citation><mixed-citation xml:lang="en">Flora SJS, Mittal M, Mehta A. Heavy metal induced oxidative stress &amp; its possible reversal by chelation therapy. Indian J Med Res. 2008;128(4):501– 523. DOI: 10.1093/jexbot/53.366.1</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Pryor WA. Oxy-radicals and related species: their formation, lifetimes, and reactions. Annu Rev Physiol. 1986;48:657–667. DOI: 10.1146/annurev.physiol.48.1.657</mixed-citation><mixed-citation xml:lang="en">Pryor WA. Oxy-radicals and related species: their formation, lifetimes, and reactions. Annu Rev Physiol. 1986;48:657–667. DOI: 10.1146/annurev.physiol.48.1.657</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Tanabe H, Nishi N, Takagi Y, et al. Purification and identification of a growth factor produced by Paramecium tetraurelia. Biochem Biophys Res Commun. 1990;170(2):786–792. DOI: 10.1016/0006-291X(90)92160-2</mixed-citation><mixed-citation xml:lang="en">Tanabe H, Nishi N, Takagi Y, et al. Purification and identification of a growth factor produced by Paramecium tetraurelia. Biochem Biophys Res Commun. 1990;170(2):786–792. DOI: 10.1016/0006-291X(90)92160-2</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Rasmussen MI, Wheatley DN. Purification and characterisation of cell survival factor 1 (TCSF1) from Tetrahymena thermophila. J Cell Commun Signal. 2007;1(3-4):185–193. DOI: 10.1007/s12079-007-0016-9</mixed-citation><mixed-citation xml:lang="en">Rasmussen MI, Wheatley DN. Purification and characterisation of cell survival factor 1 (TCSF1) from Tetrahymena thermophila. J Cell Commun Signal. 2007;1(3-4):185–193. DOI: 10.1007/s12079-007-0016-9</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Гудашева ТА, Антипова ТА, Середенин СБ. Новые низкомолекулярные миметики фактора роста нервов. Доклады Академии Наук. 2010;4(1):549–552. [Gudasheva TA, Antipova TA, Seredenin SB. Novel lowmolecular-weight mimetics of the nerve growth factor. Dokl Biochem Biophys. 2010 Sep-Oct;434:262-5. (In Russ).] DOI: 10.1134/S160767291005011X</mixed-citation><mixed-citation xml:lang="en">Гудашева ТА, Антипова ТА, Середенин СБ. Новые низкомолекулярные миметики фактора роста нервов. Доклады Академии Наук. 2010;4(1):549–552. [Gudasheva TA, Antipova TA, Seredenin SB. Novel lowmolecular-weight mimetics of the nerve growth factor. Dokl Biochem Biophys. 2010 Sep-Oct;434:262-5. (In Russ).] DOI: 10.1134/S160767291005011X</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
