Pharmacological Preconditioning by Recombinant Erythropoietin as the Possibility of Increasing the Stability of Tissue of the Retina to Reperfusion Ischemia in Experiment

Shabelnikova, A.S.; Peresypkina, Anna A.; Gubareva, V.O.; Levkova, E. A.; Должиков, А. А.; Nikolaev, S.B.; Stepchenko, Alexander A.

doi:10.18413/2313-8971-2016-2-1-25-29

Cited by 3 publications

(2 citation statements)

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“…Preconditioning (PreC) is considered as one of the promising neuroprotective approaches to increase an organism resistance to ischemia (Koch and Gonzalez 2013). PreC is a potent mobilization of the adaptive abilities of the organism pre-exposed to such factors as short-term and repeated ischemia or hypoxia episodes, which can be combined with pharmacological agents (Danilenko et al 2015, Shabelnikova et al 2016, Yang et al 2017, Korokin et al 2019, Novikov et al 2020a. It is important that there are two protective periods in PreC with differing mechanisms of their development: the early PreC period (from several min to 2 hrs) and the delayed PreC period (occurs after 24 hrs, lasts 48-72 hrs) (Shlyakhto et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Activity of ROS-induced processes in the combined preconditioning with amtizol before and after cerebral ischemia in rats

Левченкова¹,

Новиков²,

Vorobyova³

et al. 2021

RRP

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Introduction: The dose-dependent effect of reactive oxygen species (ROS) in tissues in preconditioning (PreC) and oxidative stress, as well as NO-synthase participation in mitochondrial ROS production determined the study aim – to assess the impact of the neuroprotective method of combined preconditioning (CPreC) on free radical reactions (FRRs) in brain in normoxia and in cerebral ischemia, including in NO-synthase blockade. Materials and methods: The intensity of FRR by iron-induced chemiluminescence (CL), the content of lipid peroxidation products and antioxidant enzyme activity were investigated 1 hr (early period) and 48 hrs (delayed period) after CPreC (amtizol and hypobaric hypoxia) in Wistar rat brain. Some animal groups were operated (common carotid artery bilateral ligation) 1 hr and 48 hrs after CPreC, as well as with preliminary introduction of L-NAME and aminoguanidine. Results and discussion: In normoxia, CPreC led to increase the CL maximum level (Fmax) in the delayed PreC period. The amount of thiobarbituric acid reactive products (TBA-RP), activity of superoxide dismutase (SOD) and catalase in mitochondrial fraction of rat brain did not change in comparison with the intact control in both PreC periods. In cerebral ischemia, oxidative stress was observed. The CPreC use before ischemia caused a decrease in CL parameters and TBA-RP in brain, the maintenance of SOD and high catalase activity. NO-synthase inhibitors partially abolished the antioxidant effect of CPreC in ischemia. Conclusion: CPreC had no influence on FRRs in brain tissue in normoxia, but prevented their excessive activation after ischemia, especially in the delayed period. NO-synthase was involved in the CPreC neuroprotection.

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Section: Introductionmentioning

confidence: 99%

Activity of ROS-induced processes in the combined preconditioning with amtizol before and after cerebral ischemia in rats

Левченкова¹,

Новиков²,

Vorobyova³

et al. 2021

RRP

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“…Запускаемые им каскады приводят к повышению устойчивости клеток к повреждению, что было доказано на моделях ишемии почти всех органов [3][4][5]. При ишемических поражениях разных органов EPO обусловливает ангиогенное, антиоксидантное, противовоспалительное и антиапоптотическое действие [6,7], что приводит к снижению площади повреждения [8].…”

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Evaluation of the Carbamylated Darbepoetin Acute Toxicity

Kolesnichenko¹,

Гудырев²,

Солдатов³

et al. 2019

СПНО (MPSE)

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Карбамилированный дарбэпоэтин является перспективным фармакологическим агентом с универсальной цитопротекторной активностью. Его особенностью является отсутствие стимулирующего действия на эритропоэз, которое достигается за счет избирательного взаимодействия с низкоаффинными к эритропоэтину эритропоэтиновыми рецепторами. Для оценки острой токсичности препарат был введен белым лабораторным мышам, а также белым лабораторным крысам подкожно (от 1000 до 5000 мкг/кг) и внутривенно (от 500 до 2500 мкг/кг). Исследовались все критерии в соответствии с действующими рекомендациями, дополнительно анализировались морфологическая картина внутренних органов, активность. При цитологическом исследовании мазка костного мозга в соотношении нормобластов, пронормобластов, моноцитов, сегментоядерных эозинофилов, эозинофильных миелоцитов, сегментоядерных нейтрофилов, палочкоядерных нейтрофилов и нейтрофильных миелоцитов отличий в сравнении с группой, получавшей плацебо, не выявлено. Активность животных, получавших препарат, не имела достоверных отличий от группы, получавшей плацебо. Отсутствие летальности и каких-либо фенотипических изменений (в том числе со стороны красного кровяного ростка) у обоих видов животных позволяет говорить о том, что препарат «карбамилированный дарбэпоэтин» (ООО «Фармапарк», Россия) относится к IV классу малотоксичных лекарственных веществ. Ключевые слова: эритропоэтин, карбамилированный дарбэпоэтин, крысы, гипоксия, острая токсичность Carbamylated darbepoetin is a promising pharmacological agent with universal cytoprotective activity. Its feature is the lack of a stimulating effect on erythropoiesis, which is achieved through selective interaction with low-affinity erythropoietin receptors. To assess the acute toxicity, the drug was administered to white laboratory mice, as well as white laboratory rats subcutaneously (from 1000 to 5000 μg / kg) and intravenously (500 to 2500 μg / kg). All the criteria were investigated, in accordance with the current recommendations, the morphological picture of internal organs and activity were additionally studied. In cytological examination of the bone marrow smear in the ratio of normoblasts, Pronomoblasts, monocytes, segmented nuclear eosinophils, eosinophilic myelocytes, segmented neutrophils, stab neutrophils and neutrophilic myelocytes, there were no differences in comparison with the placebo group. Activity of animals receiving the drug did not have significant differences from the group receiving placebo. The absence of lethality and any phenotypic changes (including from the red blood sprout) in both species of animals makes it possible to judge that the drug carbamylated darbepoetin (Pharmapark, Russia) belongs to the low-toxic drugs (IV class).Известно, что ишемия является одной из наиболее распространенных причин гибели и повреждения клеток. С этим связано наличие консервативных механизмов регуляции кислородного гомеостаза и гомеокинеза. Одна их этих систем, связанная с каскадом гипоксией-индуцируемого фактора, приводит к синтезу эритропоэтина (EPO), предста...

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The Study of Renoprotective Properties of Erytropoetin Derivatives on the Kidney Ischemia-Reperfusion Model

Елагин¹,

Kostina²,

Братчиков³

et al. 2018

Kuban. nauсh. med. vestnik

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Aim.The research was designed to study the renoprotective properties of erythropoietin derivatives on the kidney ischemiareperfusion experimental model.Materials and methods.The renoprotective properties of asialo erythropoietin (0.4 μg/kg and 2.4 μg/kg 30 minutes before the induction of ischemia) and carbamylated darbepoetin (50 μg/kg 24 hours before the ischemic stimulus) were studied in comparison with erythropoietin and darbepoetin in a series of experiments on male Wistar rats on a 40-minute bilateral model of renal ischemia-reperfusion. The renoprotective properties were evaluated by the results of biochemical markers of acute kidney injury, the dynamics of glomerular filtration rate and fractional sodium excretion, as well as the severity of microcirculatory disorders.Results.It was found that the prophylactic use of asialo erythropoietin (dose-dependent) and carbamylated darbepoetin leads to a decrease in the serum concentration of markers of acute renal damage, an increase in the glomerular filtration rate, a decrease in fractional sodium excretion, and a decrease in microcirculatory disorders.Conclusion.Asialo erythropoietin and carbamylated darbepoetin have the pronounced renoprotective properties and are the promising agents for the prevention and treatment of acute kidney injury.

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Pharmacological Preconditioning by Recombinant Erythropoietin as the Possibility of Increasing the Stability of Tissue of the Retina to Reperfusion Ischemia in Experiment

Cited by 3 publications

References 0 publications

Activity of ROS-induced processes in the combined preconditioning with amtizol before and after cerebral ischemia in rats

Activity of ROS-induced processes in the combined preconditioning with amtizol before and after cerebral ischemia in rats

Evaluation of the Carbamylated Darbepoetin Acute Toxicity

The Study of Renoprotective Properties of Erytropoetin Derivatives on the Kidney Ischemia-Reperfusion Model

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