A.V. Maksimenko - Dr. Sc. (Biol.), Professor, Head of Biochemical Engineering Laboratory, Institute of Experimental Car-diology, Russian Cardiology Research-and-Production Complex, Moscow, Russia. E-mail: alexmak@cardio.ru A.V. Vavaeva - Junior Research Scientist, Biochemical Engineering Laboratory, Institute of Experimental Cardiology, Russian Cardiology Research-and-Production Complex, Moscow, Russia. E-mail: labbiocheng@cardiologu.ru M.A. Zvyagintseva - Ph. D. (Biol.), Senior Research Scientist, Stem Cell Laboratory, Institute of Experimental Cardiology, Russian Cardiology Research-and-Production Complex, Moscow, Russia. E-mail: zvmaz@mail.ru A.A. Abramov - Junior Research Scientist, Experimental Myocardial Pathology Laboratory, Institute of Experimental Car-diology, Russian Cardiology Research-and-Production Complex, Moscow, Russia. E-mail: ferc_88@list.ru A.V. Vavaev - Ph.D. (Biol.), Research Scientist, Biochemical Engineering Laboratory, Institute of Experimental Cardiology, Russian Cardiology Research-and-Production Complex, Moscow, Russia. E-mail address: alex.vavaev@yandex.ru V.L. Lakomkin - Ph.D. (Med.), Leading Research Scientist, Experimental Myocardial Pathology Laboratory, Institute of Experimental Cardiology, Russian Cardiology Research-and-Production Complex, Moscow, Russia. E-mail address: la-komkin@cardio.ru

Biomedical research of superoxide dismutase-chondroitin sulphate-catalase (SOD-CHS-CAT) bienzyme conjugate was showed significantly the efficacy of its action in vivo against oxidative stress development, for the successful application of prophylaxis and medicative regime by means of intravascular administration of this derivative. The obtained results have been grounded the need of experimental evaluation in respect to efficacy of per oral prophylaxis administration of SOD-CHS-CAT conjugate on the endotoxin model injury in rats induced by lypopolysaccharide (LPS, from Salmonella enterica serotype Typhimurium) bolus. The rats have been fed for three weeks the curd with SOD-CHS-CAT conjugate (17.5 mg/kg/day, experimental group) or curd without this conjugate (control group). The intravenous bolus administration of LPS in rats has been induced the endotoxin shock development with arterial pressure decrease, heart rate increase, impairment of condition and even before the lethal termination. The comparative data (experimental and control groups) were obtained for effects of SOD-CHS-CAT bienzyme conjugate after per oral administration in rats with endotoxin shock induced by lypopolysaccharide (LPS) from Salmonella enterica serotype Typhimurium. The arterial pressure decrease was restored faster in experimental group; the alterations of heart rate were similar in both groups. The survival index (73 % in experimental and 63 % in control groups) for twenty-four hours was similar. Higher survival index (95 % in experimental and 75 % in control groups) at the 6-th hour was marked in ex-perimental group emphasizing the action celerity of SOD-CHS-CAT conjugate in vivo. These results demonstrate the possible efficacy of SOD-CHS-CAT bienzyme conjugate after per oral administration due to increase of its used dose, applying its complementary administration, complex use of means of adjacent therapy.

 

1. Maksimenko A.V.Kardiologicheskie biofarmacevtiki v koncepcii napravlennogo transporta lekarstv: prakticheskie rezultaty i issledovatelskie perspektivy // ActaNaturae. 2012. T. 4. № 3. S. 76-86.
2. Maksimenko A.V.Variacii razrabotok i primenenija terapevticheskikh belkovykh konjugatov nacelennogo dejjstvija // Rossijjskijj khimicheskijj zhurnal. 2012. T. LVI. № 3-4. S. 89-96.
3. Maksimenko A.V., Vavaev A.V., Burjachkovskaja L.I., Mokh V.P., Uchitel I.A., Lakomkin V.L., Kapelko V.I., Tishhenko E.G. Biofarmakologija fermentnykh konjugatov: Vazoprotektornaja aktivnost supramolekuljarnogo proizvodnogo superoksiddismutaza-khondroitin­sulfat-katalaza // ActaNaturae. 2010. T. 2. № 4. S. 90-103.
4. Maksimenko A.V., Vavaev A.V. Antioxidant enzymes as potential targets in cardioprotection and treatment of cardiovascular diseases. Enzyme antioxidants: the next stage of pharmacological counterwork to the oxidative stress // Heart International. 2012. V.7. P. 14-19. doi: 10.4081/hi2012.e3.
5. Vavaev A.V., Lakomkin V.L., Tishhenko E.G., Kapelko V.I., Maksimenko A.V. Vazoprotektornoe dejjstvie konjugata superoksiddismutaza-khondroitinsulfat-katalaza pri profilakticheskom i ostrom primenenii na vyzvannye peroksidom vodoroda izmenenija gemodinamiki // Tekhnologii zhivykh sistem. 2010. T. 7. № 7. S. 15-21.
6. Wardlaw J.M., Koumellis P., Liu M. Thrombolysis (different doses, routes of administration and agents) for acute ischemic stroke // Cochrane Database Syst. Rev. 2013. V. 5. CD000514. 23728633 [pmid].
7. Widimsky P., Coram R., Abou-Chebl A.Reperfusion therapy of acute ischemic stroke and acute myocardial infarction: similarities and differences // Eur. HeartJ. 2014. V. 35 (3). P. 147-155.
8. Maksimenko A.V., Vavaeva A.V., Abramov A.A., Vavaev A.V., Lakomkin V.L. Lechebnoe i preventivnoe dejjstvie bifermentnogo preparata superoksiddismutaza-khondroitinsulfat-kata­laza pri ehndotoksicheskom shoke // Tekhnologii zhivykh sistem. 2014. T. 11. № 2. S. 35-44.
9. Maksimenko A.V., Tishhenko E.G. Modifikacija katalazy khondroitinsulfatom // Biokhimija. 1997. T. 62. № 10. S. 1364-1368.
10. Rogler G., Rosano G. The heart and the gut // Eur. Heart J. 2014. V. 35 (7). P. 426-430.
11. Working Group on the Summit on Combination Therapy for CVD. Combination pharmacotherapy to prevent cardiovascular disease: present status and challenges // Eur. Heart J. 2014. V. 35(6).P. 353-364.
12. Carllion J., Rouanet J.M., Cristol J.P., Brion R. Superoxide dismutase administration, a potential therapy against oxidative stress related diseases: several routes of supplementation and proposal of an original mechanism of action // Pharm. Res. 2013. V. 30(11). P. 2718-2728.