Theoretical ground for adsorptive therapy of anthracyclines cardiotoxicity

Anthracyclines play an important role in treatment of variety types of cancer due to their high effectiveness and broad spectrum of activity. However, a major limitation of their use is the dose-limiting cardiotoxicity. The inability to predict and prevent anthracycline cardiotoxicity is in part due to the fact that the molecular and cellular mechanisms remain controversial and incompletely understood. This review focuses on the biochemical basis of the anthracyclines toxic cardiac effects and pharmacological measures to their treatment and preventing. We describe the theoretical substantiation of the enterosorption abilities for diminishing of cardiac damage

Highly activated carbon enterosorbent mediates the suppression of paraneoplastic syndrome associated with lewis lung carcinoma in mice

Aim: To investigate the effect of enterosorption on the development of paraneoplastic syndrome in mice with Lewis lung carcinoma (LLC). Materials and Methods: The study was performed on male С57/ВL6 mice with transplanted LLC. As an enterosorbent, highly activated powder fraction of HSGD was administered per os daily at a dose of 0.625 g/kg for two weeks starting from the 7th day after tumor cell transplantation. Analysis of hemo- and myelograms, morphological alterations in vital organs, the activities of catalase and superoxide dismutase, biochemical analysis of blood and quantitative analysis of hydroperoxides, malonic dialdehyde, аdvanced oxidation protein products was carried out by standard methods after completing the course of enterosorption. Ligand loading of blood plasma proteins was estimated by the method of differential scanning microcalorimetry. Results: Administration of enterosorbent resulted in inhibition of LLC growth and in nearly 2-fold decrease of lung metastases number (p < 0.05). Activation of granulocytic line in the bone marrow with nearly 3-fold enhancement of mitotic activity took place after enterosorbent administration. Red cell lineage indices and bone marrow cellularity remained unaltered. After enterosorption session, the studied biochemical indices of peripheral blood evidenced on decreasing the endogenous intoxication and oxidative stress levels, improving the functional state of kidneys, increasing the resistance of erythrocyte membranes and lowering the ligand loading of blood plasma transport proteins. Morphological structure of kidneys and liver confirmed significant positive effect of enterosorption. The data of morphologic examination of gastric fundus, small intestine, and large bowel slides after 2-week administration of enterosorbent showed its high safety and proper evacuation from intestine. Conclusion: The two-week long enterosorption session in mice with LLC caused the suppression of tumor growth and metastasis, normalization of bone marrow hemopoiesis. Enterosorption exerted a positive influence on the structural-morphologic indexes and regenerative potential of kidneys and liver, mitigated manifestations of oxidative stress, decreased the level of endogenous intoxication, promoted deliganding of albumin molecule and deloading of erythrocyte membranes

Carbon adsorbents in oncology: achievements and perspectives

The results of own investigations and literature data are summarized to determine the place of the main methods of adsorption therapy in complex treatment of the patients with malignant tumors. New possibilities for the usage of new generation of carbon adsorbents and modern adsorptive technologies in cancer treatment are discussed

Enterosorption as a method to decrease the systemic toxicity of cisplatin

A perspective adsorptive method to minimize systemic toxic effects of chemotherapy is enterosorption (ES). However, the capabilities of this method are far from being completely studied. The question remains opened — should ES be initiated in the first hours on completing cytostatic infusion without the risk of their anticancer activity to be decreased. Aim: to analyze ES influence on anticancer activity and toxic reactions of cisplatin (CP) upon the use of carbon enterosorbent in 1 h after intravenous administration of cytostatic. Methods: CP at the dose of 1 mg/kg body weigh (BW) was administered to Guerin carcinoma-bearing rats each second day for two weeks. Enterosorbents on the basis of highly activated carbon fibers were administered by per os daily 1 h after CP injection. 3 days after the last CP administration the rats were weighted and blood under ether narcosis has been taken for biochemical examination. Tumors and innate organs were isolated, weighted, and fixed in 4% buffered formalin for morphologic examination. Results: In rats administered with CP at the background of ES, BW loss was in 1.6 times lower than in animals after CP session. Relative kidney weight in CP-treated rats was 33.9% higher than in normal ones (p ≤ 0.05). No significant differences were detected between relative kidney weights in the CP + ES-treated and intact animals. Introduction of ES allowed prevent an 30% increase of creatinin content observed in blood plasma after CP treatment (р ≤ 0.05). Urea content was 1.7 times lower in blood plasma of CP + ES-treated rats than after CP treatment. CP caused significant toxic injuries in kidneys, liver, and spleen tissues. Morphologic structure of organs in rats treated with CP at the background of ES was affected at much lower degree. In tumors, large areas of newly formed connective tissue and blood vessels have been fixed after the CP+ES action instead of large necrotic area observed after CP treatment. ES caused insignificant suppression of Guerin carcinoma growth and had additional impact to inhibitory action of CP. Conclusion: Active carbon enterosorbents which are administrated just 1 h after CP administration possesses detoxicating potential sufficient for significant elimination of toxic effect of the cytostatic at the background of complete preservation of its antitumor activity

The study of possibility to elevate antitumor activity and decrease of systemic toxic effects of cisplatin by its binding with deliganded albumin

Aim: To evaluate antitumor and toxic action of cisplatin (CP) in non-bound form and in a complex with deliganded albumin. Methods: To study complex-formation between CP and albumin, differential scanning and isothermic flow microcalorimetry were used. For quantitive evaluation of albumin-bound CP, the method of ultrafiltration was applied. Concentration of platinum in the samples was determined by atomic-absorption spectral analysis. Antitumor and toxic effect of CP and CP-albumin complex was studied in vivo using Guerin carcinoma (GC) model. Results: It has been shown that the second drug-binding site, located in the III domain of albumin molecule is one of the main points of binding of CP. Purification of officinal human serum albumin (HSA) on highly active carbon hemosorbents of HSGD mark allows to obtain deliganded albumin (dHSA) with elevated complex-forming ability toward CP. Administration of CP-dHSA complex provides higher rate of GC growth inhibition, than that of CP, and the content of creatinine in blood plasma of GC-bearing rats increases by 15% versus 40% in the case of CP administration. Conclusion: The data obtained allow recommend application of CP-dHSA to complex for enhancement of antitumor action and decrease of toxic effects of cisplatin.Цель: оценить противоопухолевое и токсическое действие цисплатина (ЦП) в свободной форме и в комплексе с делигандизированным альбумином. Методы: дифференциальную сканирующую и изотермичную проточную микрокалориметрию использовали для исследования комплексообразования ЦП с альбумином. Для количественной оценки связанного с альбумином цитостатика использовали метод ультрафильтрации. Концентрацию платины в образцах определяли методом атомно-абсорбционного спектрального анализа. Противоопухолевый и токсический эффекты ЦП и ЦП в комплексе с делигандизированным альбумином изучали на крысах с карциномой Герена. Результаты: показано, что одним из основных мест связывания ЦП является второй лекарственный сайт, расположенный в III домене молекулы альбумина. Очистка фармакопейного сывороточного альбумина (ЧСА) на высокоактивных углеродных гемосорбентах марки ГСГД позволяет получить делигандизированный альбумин (дЧСА) с повышенной комплексообразующей способностью в отношении ЦП. ЦП в связанной с дЧСА форме обеспечивает повышение ингибирующего влияния цитостатика на рост карциномы Герена, при этом содержание креатинина в плазме крови повышается на 15% по сравнению с 40% при использовании несвязанного ЦП. Выводы: результаты проведенных исследований дают основания рекомендовать использование ЦП в комплексе с альбумином для усиления его противоопухолевого действия и снижения токсических эффектов

HIGHLY ACTIVATED CARBON ENTEROSORBENT MEDIATES THE SUPPRESSION OF PARANEOPLASTIC SYNDROME ASSOCIATED WITH LEWIS LUNG CARCINOMA IN MICE

Aim: To investigate the effect of enterosorption on the development of paraneoplastic syndrome in mice with Lewis lung carcinoma (LLC). Materials and Methods: The study was performed on male С57/ВL6 mice with transplanted LLC. As an enterosorbent, highly activated powder fraction of HSGD was administered per os daily at a dose of 0.625 g/kg for two weeks starting from the 7th day after tumor cell transplantation. Analysis of hemo- and myelograms, morphological alterations in vital organs, the activities of catalase and superoxide dismutase, biochemical analysis of blood and quantitative analysis of hydroperoxides, malonic dialdehyde, аdvanced oxidation protein products was carried out by standard methods after completing the course of enterosorption. Ligand loading of blood plasma proteins was estimated by the method of differential scanning microcalorimetry. Results: Administration of enterosorbent resulted in inhibition of LLC growth and in nearly 2-fold decrease of lung metastases number (p < 0.05). Activation of granulocytic line in the bone marrow with nearly 3-fold enhancement of mitotic activity took place after enterosorbent administration. Red cell lineage indices and bone marrow cellularity remained unaltered. After enterosorption session, the studied biochemical indices of peripheral blood evidenced on decreasing the endogenous intoxication and oxidative stress levels, improving the functional state of kidneys, increasing the resistance of erythrocyte membranes and lowering the ligand loading of blood plasma transport proteins. Morphological structure of kidneys and liver confirmed significant positive effect of enterosorption. The data of morphologic examination of gastric fundus, small intestine, and large bowel slides after 2-week administration of enterosorbent showed its high safety and proper evacuation from intestine. Conclusion: The two-week long enterosorption session in mice with LLC caused the suppression of tumor growth and metastasis, normalization of bone marrow hemopoiesis. Enterosorption exerted a positive influence on the structural-morphologic indexes and regenerative potential of kidneys and liver, mitigated manifestations of oxidative stress, decreased the level of endogenous intoxication, promoted deliganding of albumin molecule and deloading of erythrocyte membranes

Obtaining and analysis of товассо, lettuce and rape plants transformed with human interferon alfa 2b gene

Plasmid constructs for Agrobacterium-mediated transformation of plant nuclear genome with human interferon alpha2b gene were built up and used to obtain transgenic plants of tobacco, lettuce and rape. Presence of the target gene was confirmed by PCR analysis and interferon activity in lettuce plants was shown by the vesicular stomatitis virus cytopathic effect assay.Сконструйовані вектори для Agrobacterium-опосередкованої трансформації ядерного геному рослин геном інтерферону альфа 2b людини були використані для отримання трансгенних рослин тютюну, салату та ріпаку. Присутність цільового гену було показано за допомогою ПЛР аналізу. Трансформовані рослини салату демонстрували антивірусну активність інтерферону.Сконструированные вектора для Agrobacterium-опосредованной трансформации ядерного генома растений геном интерферона альфа 2b человека были использованы для получения трансгенных растений табака, салата и рапса. Присутствие целевого гена было показано с помощью ПЦР анализа. Трансформированные растения салата демонстрировали антивирусную активность интерферона