Homeovox, a multicomponent homeopathic treatment for laryngitis of various etiologies, was tested for allergenic properties and immunotoxicity. Methods . 80 male albino guinea pigs and 180 male СВА, C57BL/6 and F1 hybrid (CBAхС57BL/6) mice were used in the study. In order to assess immunotoxicity, Homeovox was administrated orally to mice for 14 days at doses of 100 mg/kg and 1 000 mg/kg. To assess the allergenic properties of Homeovox, albino guinea pigs were also given the drug at doses of 100 mg/kg and 1 000 mg/kg according to the standard immunization schedules. Results . Oral administration of Homeovox to mice for 14 days at doses of 100 mg/kg and 1 000 mg/kg did not cause significant changes in the main characteristics of immune response compared to controls. When assessing allergenicity, Homeovox at doses 100 mg/kg and 1 000 mg/kg administered according to the standard immunization schedules did not induce systemic anaphylaxis or active skin anaphylaxis in albino guinea pigs. The immunization of guinea pigs by Homeovox at the same doses in a mixture with Freund's complete adjuvant caused no delayed allergic reactions. Homeovox at a single oral dose of 1 000 mg/kg significantly decreased concanavalin A-induced inflammation in CBA mice by 58.4 %. Conclusion . Within the dosage range investigated, Homeovox does not induce immunotoxicity, immediate- or delayed-type allergic or pseudoallergic reactions.
Осуществлен синтез 2-изобутил-4,6-диметил-5-оксипиримидина (СНК-411) и его соли (СНК-578). В опытах на мышах-самцах С57BL/6 на модели меланомы В16 изучено противоопухолевое и антиметастатическое действие нового производного 5-оксипиримидина СНК-578. Стандартная прививочная доза составила 5 106 опухолевых клеток на мышь. СНК-578 вводили внутрибрюшинно (в/б) в дозах 10 и 25 мг/кг в течение 2 недель со 2 по 15 дни развития меланомы В16. В качестве позитивного контроля и для выявления аддитивного эффекта от совместного однократного применения доксорубицина и курсового введения СНК-578 мышам вводили доксорубицин в дозе 4 мг/кг на 2-й день развития опухоли. Совместное курсовое в/б введение СНК-578 в дозе 10 мг/кг и однократное в/б введение доксорубицина в дозе 4 мг/кг выявило достоверное уменьшение роста опухоли, что выразилось в уменьшении объема опухоли в 2,4, 1,9 и 1,5 раза на 11, 15 и 21 дни опыта, по сравнению с группой активного контроля, не получавшей препараты СНК-578 обладает выраженной антиметастатической активностью в дозах 10 и 25 мг/кг при монотерапии и при совместном введении с доксорубицином в дозе 4 мг/кг. Индекс ингибирования метастазирования (ИИМ) при введении СНК-578 в дозе 10 мг/кг составил 75,8 %, в дозе 25 мг/кг – 92,3 %. Наиболее выраженный антиметастатический эффект был обнаружен при совместном в/б введении СНК-578 в течение 14 дней в дозе 10 мг/кг и однократном введении доксорубицина в дозе 4 мг/кг. У 6 из 9 мышей на 21 день развития меланомы В16 метастазы отсутствовали, у 3 обнаружили по 1, 2 и 3 очень мелкие метастазы, подавление метастазирования — на 98,9 %.
Introduction. Imbalance of Th1/Th2 lymphocytes and cytokines is responsible for increasing rate of pathology such as allergy, autoimmune processes and oncology. It is known that pyrimidines have a wide spectrum of pharmacological activity, for example they are capable of exerting antiallergic activity. Aim. The aim of this study is to investigate effects of 5-hydroxypyrimidine derivatives on systemic anaphylaxis, concentrations of immunoglobulin E and cytokines in comparison with Aerius in experiments on ovalbumin-induced systemic anaphylaxis model. Materials and methods. Effects of 7-day course of intraperitoneal (ip) administration of SNK-411, SNK-578 in doses of 25 mg/kg and 50 mg/kg and Aerius ip. in dose of 1,3 mg/kg was studied on 140 male Balb/c mice sensitized using ovalbumin. 120 mice were immunized by two injections (two-week interval between injections) of ovalbumin (100 mg per mouse) mixed with aluminum hydroxide (5 mg per mouse). 20 mice were used as intact control. Administration of SNK-411, SNK-578 and Aerius began after second immunization and lasted for 7 days. In one hour after last injection of studied compounds 70 mice received intravenous injection of ovalbumin (100 mg dissolved in 0,1 ml saline) in retroorbital venous sinus. 70 mice from control and experimental groups were euthanized by decapitation. Immunoglobulin E (IgE), Interleukin-2 (IL-2), IL-4, IL-5, IL-6, IL-10, IL-11, IL-17A, IL-17F, Interferon gamma (IFN-γ), IL-13 concentrations were studied on BD FACSCanto II flow cytometer (“BD Biosciences”, USA). Results. Administration of SNK-411 and SNK-578 in doses of 50 mg/kg decreased severity of systemic anaphylaxis reaction, lowered serum concertation of IgE in 1.5-1.6 times compared to ovalbumin control group. Administration of Aerius have not decreased serum concertation of IgE. Th-1 cytokines, IFN-γ, IL-2 were decreased in ovalbumin control group while serum concentration of Th-2 cytokines (IL-4, IL-5, IL-13) and proinflammatory IL-6 were higher compared to intact control group. Course administration of SNK-411, SNK-578 in doses of 25 mg/kg and 50 mg/kg and Aerius decreased serum concentration of Th-2 cytokines (IL-4, IL-5, IL-13) compared to ovalbumin control group. SNK-411 and SNK-578 in doses of 25 mg/kg and 50 mg/kg increased serum level of IL-2, administration of SNK-578 in dose of 50 mg/kg also increased concentration of IFN-γ up to intact control level and decreased concentration of IL-6. SNK-411 and SNK-578 lowered levels of IL-11 compared to ovalbumin control group. SNK-411 lowered level of IL-17A. Conclusions. 7-day administration of 5-hydroxypyrimidine derivatives in dose of 50 mg/kg decreased severity of systemic anaphylaxis. SNK-411, SNK-578 and Aerius lowered levels of proallergic cytokines in serum of sensitized mice. 5-hydroxypyrimidine derivatives in contrast to Aerius decreased immunoglobulin E concentration.
Материалы V съезда фармакологов России «Научные основы поиска и создания новых лекарств» (14-18 мая 2018 года, г. Ярославль)
Материалы V съезда фармакологов России «Научные основы поиска и создания новых лекарств» (14-18 мая 2018 года, г. Ярославль)
Материалы V съезда фармакологов России «Научные основы поиска и создания новых лекарств» (14-18 мая 2018 года, г. Ярославль)
