actabiomedicaActa Biomedica ScientificaActa Biomedica Scientifica2541-94202587-9596Scientific Centre for Family Health and Human Reproduction Problems10.12737/article_590823a4d95e23.38896065actabiomedica-201Research ArticleЭКСПЕРИМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯ В БИОЛОГИИ И МЕДИЦИНЕEXPERIMENTAL RESEARCHES IN BIOLOGY AND MEDICINEНаправления защитного действия биферментного конъюгата антиоксидантных биокатализаторов in vivoProtective action of bienzyme conjugate of antioxidant biocatalysts in vivoМаксименкоА. В.MaksimenkoA. V.alexmak@cardio.ruВаваеваА. В.VavaevaA. V.noemail@neicon.ruАбрамовА. А.AbramovA. A.noemail@neicon.ruТимошинА. А.TimoshinA. A.noemail@neicon.ruЗвягинцеваМ. А.ZvyagintsevaM. A.noemail@neicon.ruЛакомкинВ. Л.LakomkinV. L.noemail@neicon.ruФГБУ «Российский кардиологический научно-производственный комплекс» Минздрава РоссииRussian Cardiology Research and Production Complex20162805201613(2)116119Copyright © Максименко А.В., Ваваева А.В., Абрамов А.А., Тимошин А.А., Звягинцева М.А., Лакомкин В.Л., 20162016Максименко А.В., Ваваева А.В., Абрамов А.А., Тимошин А.А., Звягинцева М.А., Лакомкин В.Л.Maksimenko A.V., Vavaeva A.V., Abramov A.A., Timoshin A.A., Zvyagintseva M.A., Lakomkin V.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.actabiomedica.ru/jour/article/view/201

Развитие эндотоксического шока у крыс, индуцированного введением бактериального липополисахарида, сопровождалось окислительным стрессом и повышениемуровня NO в печени, легких, почках, сердце животных. Введение в лечебном режиме антиоксидантного конъюгата супероксиддисмутаза - хондроитинсульфат - каталаза (СОД-ХС-КАТ) значимо не меняло эти показатели, а по изменению содержания в крови мочевины и креатинина оказывало защитное действие на функцию почек.

Endotoxin shock in rats led to intravenous bolus of bacterial lipopolysaccharide (LPS) was accompanied by oxidative stress and increase of NO level in livers, lungs, kidneys, hearts of animals. The intravenous administration of bienzyme superoxide dismutase - chondroitin sulphate - catalase conjugate (SOD-CHS-CAT) showed its anti-endotoxemia action in rats at preventive (before initiation of injury) and therapeutic (after start of injury) application during cytokine phase of injury and influence on further stages of the damage. The injection of antioxidant SOD-CHS-CAT conjugate in a therapeutic regime did not demonstrate significant alterations of No level in livers, lungs, kidneys, hearts of rats (as compared to indices of the rat group with LpS action only) and displayed protective action on the kidney function by altered urea and creatinine in blood. The therapeutic effect of SOD-CHS-CAT was demonstrated by increase in organism viability. The effects of intravenous injection of SOD-CHS-CAT in a rat model of endotoxin shock showed a variety in the activity of this conjugate in addition to prevention of NO conversion in peroxynitrite upon interaction with O2 superoxide radical. The results of accelerated normalization of arterial blood pressure and heart rate, a significant decrease in rat lethality because of using SOD-CHS-CAT conjugate indicate the importance of the determination of action mechanism of the cardiovascular injury models associated with other vasoactive agents besides NO. The further research of vascular damage pathogenesis and evaluation of its role in oxidative stress (time and place) are of paramount importance.

липополисахаридэндотоксический шококислительный стрессантиоксидантыбиферментный конъюгат супероксиддисмутаза - хондроитинсульфат - каталазаNO-зависимое и NO-независимое защитное действиеlipopolysaccharideendotoxin shockoxidative stressantioxidantsbienzyme superoxide dismutase-chondroitin sulfate-catalase conjugateReferencesМаксименко А.В. Кардиологические биофармацевтики в концепции направленного транспорта лекарств: практические результаты и исследовательские перспективы // Acta Naturae. - 2012. - Т. 4, № 3. - C. 76-86Максименко А.В. Кардиологические биофармацевтики в концепции направленного транспорта лекарств: практические результаты и исследовательские перспективы // Acta Naturae. - 2012. - Т. 4, № 3. - C. 76-86Максименко А.В. Внеклеточное оксидативное поражение сосудистой стенки и её ферментативная антиоксидантная защита // Химико-фармацевтический журнал. - 2007. - Т. 41, № 5. - С. 3-12Максименко А.В. Внеклеточное оксидативное поражение сосудистой стенки и её ферментативная антиоксидантная защита // Химико-фармацевтический журнал. - 2007. - Т. 41, № 5. - С. 3-12Максименко А.В., Ваваев А.В., Бурячковская Л.И., Мох В.П., Учитель И.А., Лакомкин В.Л., Капелько В.И., Тищенко Е.Г. Биофармакология ферментных конъюгатов: вазопротекторная активность супрамолекулярного производного супероксиддисмутаза-хондроитинсульфат-каталаза // Acta Naturae. -2010. - Т. 2, № 4. - C. 90-103Максименко А.В., Ваваев А.В., Бурячковская Л.И., Мох В.П., Учитель И.А., Лакомкин В.Л., Капелько В.И., Тищенко Е.Г. Биофармакология ферментных конъюгатов: вазопротекторная активность супрамолекулярного производного супероксиддисмутаза-хондроитинсульфат-каталаза // Acta Naturae. -2010. - Т. 2, № 4. - C. 90-103Максименко А.В., Ваваева А.В., Абрамов А.А., Ваваев А.В., Лакомкин В.Л. Лечебное и превентивное действие биферментного препарата супероксиддисмутаза-хондроитинсульфат-каталаза при эндотоксическом шоке // Технологии живых систем. - 2014. -Т. 11, № 2. - С. 35-44Максименко А.В., Ваваева А.В., Абрамов А.А., Ваваев А.В., Лакомкин В.Л. Лечебное и превентивное действие биферментного препарата супероксиддисмутаза-хондроитинсульфат-каталаза при эндотоксическом шоке // Технологии живых систем. - 2014. -Т. 11, № 2. - С. 35-44Baraune VG, Campos LCG, Miyakawa AA, Krieger JE (2011). ACE as a mechanosensor to shear stress influences the control of its own regulation via phosphorylation of cytoplasmic Ser12. PLoS One, 6 (8), e22803.Baraune VG, Campos LCG, Miyakawa AA, Krieger JE (2011). ACE as a mechanosensor to shear stress influences the control of its own regulation via phosphorylation of cytoplasmic Ser12. PLoS One, 6 (8), e22803.Bice JS, Keim Y, Stasch J-P, Baxter GF (2014). NO-independent stimulation or activation of soluble quanylyl cyclase during early reperfusion limits infarct size. CardiovascuaResearnh, (101), 220-228.Bice JS, Keim Y, Stasch J-P, Baxter GF (2014). NO-independent stimulation or activation of soluble quanylyl cyclase during early reperfusion limits infarct size. CardiovascuaResearnh, (101), 220-228.Brito R, Castillo G, Gonzales J, Valls N, Rodrigo R (2015). Oxidative stress in hypertension: mechanism and therapeutic opportunities. Experimental and Clinical Endocrinology & Diabetes, 123 (6), 325-335.Brito R, Castillo G, Gonzales J, Valls N, Rodrigo R (2015). Oxidative stress in hypertension: mechanism and therapeutic opportunities. Experimental and Clinical Endocrinology & Diabetes, 123 (6), 325-335.Carillon J, Rouanet JM, Cristol JP, Brion R (2013). Superoxide dismutase administration, a potential therapy against oxidative stress related diseases: several routes of supplementation and proposal of an original mechanism of action. PhamaceuticalResearnh, 30 (11), 2718-2728.Carillon J, Rouanet JM, Cristol JP, Brion R (2013). Superoxide dismutase administration, a potential therapy against oxidative stress related diseases: several routes of supplementation and proposal of an original mechanism of action. PhamaceuticalResearnh, 30 (11), 2718-2728.Ekelof S, Jensen SE, Rosenberg J, Gogenur I (2014). Reduced oxidative stress in STEMI patients treated by primary percutaneous coronary intervention and with antioxidant therapy: a systematic review. Cardiovascular Drugs and Therapy, 28 (12), 173-181.Ekelof S, Jensen SE, Rosenberg J, Gogenur I (2014). Reduced oxidative stress in STEMI patients treated by primary percutaneous coronary intervention and with antioxidant therapy: a systematic review. Cardiovascular Drugs and Therapy, 28 (12), 173-181.Kimura S, Zhang G-X, Abel Y (2004). Malfunction of vascular control in lifestyle-related diseases: oxidative stress of angiotensin-II - induced hypertension: mitogen activated protein kinase and blood pressure regulation. Journal of Pharmaceutical Sciences, (96), 406-410.Kimura S, Zhang G-X, Abel Y (2004). Malfunction of vascular control in lifestyle-related diseases: oxidative stress of angiotensin-II - induced hypertension: mitogen activated protein kinase and blood pressure regulation. Journal of Pharmaceutical Sciences, (96), 406-410.Maksimenko AV (2005). Experimental antioxidant biotherapy for protection of the vascular wall by modified forms of superoxide dismutase and catalase. Current Phamaceutical Design, 11 (16), 2007-2016.Maksimenko AV (2005). Experimental antioxidant biotherapy for protection of the vascular wall by modified forms of superoxide dismutase and catalase. Current Phamaceutical Design, 11 (16), 2007-2016.Maksimenko AV, Vavaev AV (2012). Antioxidant enzymes as potential targets in cardioprotection and treatment of cardiovascular diseases. Enzyme antioxidants: the next stage of pharmacological counterwork to the oxidative stress. Heari International, (7), 14-19. DOI: 10.4081/hi.2012.e3.Maksimenko AV, Vavaev AV (2012). Antioxidant enzymes as potential targets in cardioprotection and treatment of cardiovascular diseases. Enzyme antioxidants: the next stage of pharmacological counterwork to the oxidative stress. Heari International, (7), 14-19. DOI: 10.4081/hi.2012.e3.Münzel T, Gori T, Keaney JF Jr., Maack C, Daiber A. (2015). Pathophysiological role of oxidative stress in systolic and diastolic heart failure and its therapeutic implementation. European Heart Journal, 36 (38), 2555-2564.Münzel T, Gori T, Keaney JF Jr., Maack C, Daiber A. (2015). Pathophysiological role of oxidative stress in systolic and diastolic heart failure and its therapeutic implementation. European Heart Journal, 36 (38), 2555-2564.Siti HN, Kamisah Y, Kamsiah J (2015). The role of oxidative stress, antioxidants and vascular inflammation in cardiovascular disease (a review). Vascular Pharmacology, (71), 40-56.Siti HN, Kamisah Y, Kamsiah J (2015). The role of oxidative stress, antioxidants and vascular inflammation in cardiovascular disease (a review). Vascular Pharmacology, (71), 40-56.Yamashita T, Sato T, Sakamoto K, Ishii H, Yamamoto J (2015). The free-radical scavenger edaravone accelerates thrombolysis with alteplase in experimental thrombosis model. Thrombosis Research, 135 (6), 1209-1213.Yamashita T, Sato T, Sakamoto K, Ishii H, Yamamoto J (2015). The free-radical scavenger edaravone accelerates thrombolysis with alteplase in experimental thrombosis model. Thrombosis Research, 135 (6), 1209-1213.

The authors declare that there are no conflicts of interest present.