Antihypoxic Activity Research Articles

Synthesis of targeted doxorubicin-loaded gold nanorod −mesoporous manganese dioxide core–shell nanostructure for ferroptosis, chemo-photothermal therapy in vitro and in vivo

In the current study, a core–shell inorganic nanostructure comprising a gold nanorod core and −mesoporous manganese dioxide shell was synthesized. Then, the mesoporous manganese dioxide shell was loaded with doxorubicin (DOX) and then coated with pluronic F127 and pluronic F127-folic acid conjugate (1.5:1 wt ratio of pluronic F127: pluronic F127-folic acid conjugate) to prepare targeted final platform. In this design, mesoporous manganese dioxide acted as a reservoir for DOX loading, anti-hypoxia, and MRI contrast agent, while the gold nanorod core acted as a photothermal and CT scan imaging agent. DOX was encapsulated in the mesoporous manganese dioxide shell with a loading capacity and loading efficiency of 19.8 % ± 0.2 and 99.0 % ± 0.9, respectively. The in vitro release experiment showed the impact of glutathione (GSH), mildly acidic pH, and laser irradiating toward accelerated stimuli-responsive DOX release. The ·OH production of the prepared platform was verified by methylene blue (MB) decomposition reaction. Furthermore, thermal imaging exhibited the ability of the prepared platform to convert the NIR irradiation to heat. In vitro cytotoxicity tests on the folate receptor-positive 4 T1 cell line revealed the remarkable cytotoxicity of the targeted formulation compared to the nontargeted formulation (statistically significant). The MTT experiment demonstrated that exposure to laser 808 irradiation enhanced cytotoxicity of the targeted formulation (p < 0.0001). The production of ROS in 4 T1 cells following treatment with the targeted formulation was demonstrated by the dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay. Furthermore, in vivo investigations by implementing subcutaneous 4 T1 tumorized female BABL/c mice indicated that the prepared platform was an effective system in suppressing tumor growth by combining chemotherapy with PTT (photothermal therapy). Additionally, simultanous PTT and anti-hypoxic activity of this system showed potent tumor growth suppression impact. The percent of tumor size reduction in mice treated with FA-F127-DOX@Au-MnO2 + 808 nm laser compared to the control group was 99.7 %. The results of the biodistribution investigation showed tumor accumulation and modified pharmacokinetics of the targeted system. Lastly, 6 and 24 h post-intravenous injection, CT-scan and MR imagings capability of the prepared platform was verified in preclinical stage. The prepared multipurpose system introduces great opportunity to provide multiple treatment strategy along with multimodal imaging capability in a single platform for breast cancer treatment.

The preliminary introduction of hydrogen peroxide into the stomach of aquarium fish increases their survival rate in conditions of acute hypoxia

BACKGROUND: A solution of 3% hydrogen peroxide is an over-the-counter oxygen-releasing antiseptic, which forms oxygen foam when interacting locally with the wound surface. Therefore, this drug is widely used for mechanical cleansing of the surface of chronic wounds from purulent masses. The release of oxygen during catalase cleavage of hydrogen peroxide indicates the possibility of achieving anti-ischemic and anti-hypoxic action. AIM: A study of the effect of intragastric hydrogen peroxide on the resistance of aquarium fish to acute hypoxia. MATERIALS AND METHODS: Experiments were conducted on 80 adult aquarium fish of the guppy, blue neon, tri-linear parsings, swordtail fish and zebrafish (Danio rerio) breeds. To create acute hypoxia, each fish was placed in a transparent plastic container containing 5, 10 or 20 ml of fresh water at a temperature of +25 - +26 °C together with the fish, after which the container was hermetically sealed. Then, the motor activity of the fish's body, the respiratory movements of the gill arches, the opening of the oral cavity, the fluctuations of the fins and the dynamics of their coloration were monitored until the complete final immobilization of the fish and their death. Immediately before the experiment, 0.05 or 0.1 ml of fresh water in the control series and 0.05 ml or 0.1 ml of 0.05% hydrogen peroxide solution in the experimental series were injected into the stomach of the fish. The liquid was injected into the fish's stomach using a gastric mini-probe connected to an insulin syringe. RESULTS: It is shown that aquarium fish retain their viability in a small volume of fresh water inside a hermetically sealed container for a limited period of time, since fish continuously consume oxygen dissolved in water, thereby deepening hypoxia. At the same time, after sealing the container, the fish very quickly assume a stationary state, in which they remain for a certain period of time until their death. However, just before death, the immobility of the fish is disturbed. At the same time, the fish suddenly appear convulsive body movements, active movements of pectoral fins, mouths and gill arches, pectoral fins change their color, after which the fish defecate into the water. The results showed that the preliminary injection of 0.05 or 0.1 ml of 0.05% hydrogen peroxide solution into the stomach of fish prolongs the period of immobility of fish in hypoxia by an average of 20%. In all likelihood, the immobile state of fish is part of the complex of their adaptive adjustment to the cessation of oxygen supply to the water and reflects the availability of reserves of adaptation to hypoxia. The fact is that the absence of muscle contractions stops the muscles from using oxygen, which they use to generate energy. It is assumed that inside the stomach, hydrogen peroxide is absorbed into the blood, where, under the action of the enzyme catalase, it is split into water and gaseous oxygen, which replaces oxygen in the gills in the absence of oxygen in the surrounding water. CONCLUSIONS: Under model conditions, it was shown that pre-administration of 0.05 or 0.1 ml of 0.05% hydrogen peroxide solution into the stomach of fish increases their survival in conditions of acute hypoxia. Therefore, hydrogen peroxide can be considered as a potential antihypoxant for prolonging life in various types of suffocation, including the final stage of COVID-19.

Toxicity and Antihypoxic Activity of a Preparation Containing a Complex Compound of 5-Hydroxy-6-Methyluracil with N-Acetyl Cysteine

Toxicity and Antihypoxic Activity of a Preparation Containing a Complex Compound of 5-Hydroxy-6-Methyluracil with N-Acetyl Cysteine

Dammarane-type triterpenoids from Gynostemma longipes and their protective activities on hypoxia-induced injury in PC12 cells

Sixteen new dammarane-type triterpenoid saponins (1–16) featuring diverse structural variations in the side chain at C-17, along with twenty-one known analogues (17–37), have been isolated from the rhizomes of Gynostemma longipes C. Y. Wu, a plant renowned for its medicinal and edible properties. The structural elucidation of these compounds was accomplished through comprehensive analyses of 1D and 2D NMR and HRMS spectroscopic data, supplemented by comparison with previously reported data. Subsequent assays on the isolates for their protective effects against hypoxia-induced damage in pheochromocytoma cells (PC12 cells) revealed that nine saponins exhibited significant anti-hypoxic activities. Further investigation into the anti-hypoxia mechanisms of the representative saponins demonstrated that compounds 22 and 36 markedly reduced the levels of hypoxia-induced apoptosis. Additionally, these compounds were found to decrease the release of lactate dehydrogenase (LDH) and malondialdehyde (MDA), while increasing the activity of superoxide dismutase (SOD), thereby indicating that the saponins could mitigate hypoxia-induced injuries by ameliorating apoptosis and oxidative stress. These findings offer substantial evidence for the future utilization and development of G. longipes, identifying dammarane-type triterpenoid saponins as its active anti-hypoxic constituents.

Iodine-induced synthetic method and pharmacokinetic study of cis- and trans-crocetin.

This experiment aimed to obtain the relatively rare cis-crocetin isomer from natural plants, which predominantly exist in the more stable all-trans configuration. This was achieved through iodine-induced isomerization, followed by purification and structural identification. The study also aimed to compare the pharmacokinetic differences between cis- and trans-crocetin in vivo. Trans-crocetin of high purity was extracted by hydrolysis from gardenia yellow pigment. Cis-crocetin was then synthesized through an optimized electrophilic addition reaction induced by elemental iodine, and subsequently separated and purified via silica gel column chromatography. Structural identification of cis-crocetin was determined using IR, UV, and NMR techniques. In vivo pharmacokinetic studies were conducted for both cis- and trans-crocetin. In addition to this, we have conducted a comparative study on the in vivo anti-hypoxic activity of trans- and cis-crocetin. Under the selected reaction conditions using DMF as the solvent, with a concentration of 2.5mg/mL for both trans-crocetin and the iodine solution, and adjusting the illumination time according to the amount of trans-crocetin, the rate of iodine-induced isomerization was the fastest. Cis-crocetin was successfully obtained and, after purification, its structure was identified and found to be consistent with reported data. Cis-crocetin exhibited a faster absorption rate and higher bioavailability, and despite its shorter half-life, it could partially convert to trans-crocetin in the body, thereby extending the duration of the drug's action within the body to some extent. This study accomplished the successful preparation and structural identification of cis-crocetin. Additionally, through pharmacokinetic studies, it uncovered notable variations in bioavailability between cis- and trans-crocetin. These findings serve as a solid scientific foundation for future functional research and practical applications in this field.

Pathogenetic and pharmacodynamic features of succinic acid derivative application for various diseases of the cardiovascular and nervous systems

This study revealed the pathogenetic patterns of the development of hypoxic and ischemic disorders in various pathological conditions and substantiated approaches to the use of drugs with antihypoxic activity. The role of the receptor interaction of succinic acid in the composition of succinate-containing antihypoxants with succinate receptor SUCNR1 has been demonstrated. The pharmacodynamic properties of the combined preparation of succinic acid that also contains vitamin precursors of the cofactors of Krebs cycle dehydrogenases nicotinamide (precursor of NAD) and riboflavin mononucleotide (precursor of FAD) and precursor of purine nucleotides (inosine) (cytoflavin) for intravenous drip and oral administration were analyzed. Literature data were also analyzed to evaluate the effectiveness of the use of the metabolic corrector of energy-dependent and hypoxic conditions (cytoflavin) in various central nervous system and cardiovascular diseases. In the case of ischemic disorders of cerebral and coronary blood flow, the effects of the drug are concentrated on the penumbra zone (ischemic penumbra), which is associated with the intravenous administration of the drug to its metabolic activity by influencing endothelial cells, restoring microcirculation, and enhancing the oxygen transport function of the blood. Among the new areas of drug use, the use of cytoflavin in the complex therapy of traumatic brain injuries, traumatic shock, acute respiratory distress syndrome, toxic lesions of the central nervous system, multiple organ failure syndrome, and post-COVID syndrome is promising.

The regulatory effects of mesedin and beditin alpha2-adrenoblockers on the functional activity of the nervous, cardiovascular, and endocrine systems in rats under the hypoxic conditions.

One of the reasons of the development of pathologies causing death is hypoxia. The purposes of this study were (1) to study some physiological and biochemical mechanisms of α2-adrenoblockers, which ensure the tissue resistance increase to hypoxia; (2) to offer new drugs contributing to the increase of tissues' stability towards the hypoxic affection; and (3) to submit new medications to surpass by their anti-hypoxic activity of those already used in modern medicine and have some advantages. The reactivity of postsynaptic vascular α2-adrenoceptors was determined on the damaged spinal cord expressed by the blood pressure increase in response to intravenous administration of azepexole that selectively binds to α2-adrenoceptors. Determination of the systemic hemodynamic values and the vascular resistance to the blood flow was performed by the method with plastic microspheres of marked isotopes. pO2 in the blood and the oxygen-transporting function were determined in a sample of 0.1ml of blood in 30, 90, and 180min after the α2-adrenoblockers' injections. It has been found that one of the major hemodynamic effects of mesedin and beditin was an improvement in cardiac output, as well as a prolonged increase in coronary blood flow and vasodilation of the heart vessels. Some anti-hypoxic mechanisms of the studied α2-adrenoblockers are an improvement of blood oxygen-transporting function followed by tissue oxygenation and the increased level of corticosterone and resistance to hypoxia. Revealing the mechanisms of action of the postsynaptic α2-adrenoceptors suggests that mesedin and beditin are potentially effective therapeutic means for many hypoxic conditions.

Assessment of Antihypoxic Activity of S-analoges of Dihydropyrimidin-2-ones and Their Condensed Derivatives

Introduction. Antioxydant activity, membrane stabilizing and cytoprotective effect of dihydropyrimidin analoges are widely described in various literary sources. One of the importantant mechanisms of action of antioxidants is their antihypoxic activity. It is the ability to increase tissue resistance to hypoxia. The search for drugs to increase the body's resistance under hypoxic conditions is an actual task in experimental and clinical pharmacology.Aim. Study of the antihypoxic activity of new S-analogs of dihydropyrimidin-2-ones and their condensed derivatives in various models of hypoxia.Materials and methods. 13 compounds S-analogs of dihydropyrimidin-2-ones and their condensed derivatives are objects of research. Their structure has been confirmed by spectroscopy methods. The antihypoxic activity was carried out by recommended methods for preclinical study of new pharmacological substances.Results and discussion. This paper presents the results of testing the obtained compounds of different structures on three models of hypoxia. The activity of a number of condensed tricyclic derivatives of dihydropyrimidine-2-thiones was studied in more detail using a model of acute normobaric hypoxia with hypercapnia.Conclusion. The compounds did not demonstrate high antihypoxic activity; some «structure-property» patterns were revealed.

Synthesis and Antihypoxic Activity of 2-aryl-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydroquinoline-4-carboxylic Acids and Their Reaction Products with Substituted Hydrazines

Introduction. Hypoxia is a violation of oxidative processes in tissues that occur when oxygen is insufficiently supplied to them or when its utilization is disrupted during biological oxidation. Chronic hypoxic damage plays an important role in the occurrence and development of various diseases, which necessitates the synthesis of new compounds with antihypoxic activity.Aim. The purpose of this study is to synthesize and investigate the antihypoxic activity of 2-aryl-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydroquinoline-4-carboxylic acids and their reaction products with substituted hydrazines.Materials and methods. 2-Aryl-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydroquinoline-4-carboxylic acids (I–VI) were obtained with high yields as a result of the interaction of 4-aroyl-2,4-dioxobutane acids with 3-amino-5,5-dimethylcyclohex-2-enone. Interaction of 2-aryl-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydroquinoline-4-carboxylic acids with benzyl- and (2-phenylethyl)hydrazines 5-aryl-2-benzyl- and 2-(2-phenylethyl)-8,8-dimethyl-3,7,8,9-tetrahydro-2H-pyrido[4,3,2-de]cinnoline-3-ones (VII–XII) were obtained. As a result, 12 compounds were synthesized. The study of the antihypoxic activity of the obtained compounds was carried out in vivo on a model of normobaric hypoxia with hypercapnia.Results and discussion. The synthesized compounds were tested for the presence of antihypoxic action. The most pronounced antihypoxic activity is characteristic of compounds VI and VIII, which have a methoxy group and a methyl radical in the para-position of the phenyl substituent at C5, respectively. The presence of chlorine in the structure of compound III, fluorine in compound X and the absence of substituents (compounds I and VII) contribute to the prohypoxic effect. According to the results of the study, both quinolincarboxylic acids and pyridocinnolines are potential antihypoxants.Conclusion. A comparative analysis of the antihypoxic activity of the synthesized compounds was carried out, the relationship between their structure and severity of action was established, the most active substances were identified.

Protective effect of heme chloride on hypoxia-induced tissue injury in mice.

Heme chloride (Hemin) is an in vitro purified form of natural heme and an important raw material for anti-anemia and antitumor drugs. This study aims to analyze the protective effect of Hemin on tissue damage in low-pressure oxygen chamber simulated plateau hypoxic mice, and explore its role in anti-plateau hypoxia. Thirty male BALB/c mice were randomly divided into a blank group, a positive drug group (acetazolomide, 200 mg/kg), a Hemin low-dose group (15 mg/kg), a Hemin medium-dose group (30 mg/kg), and a Hemin high-dose group (60 mg/kg) with intraperitoneal injection. The anti-hypoxic activity of Hemin was explored by atmospheric closed hypoxia experiment and the optimal dose was screened. Thirty-six male BALB/c mice were randomly divided into a blank group, a hypoxia group, a positive drug group, and a Hemin high-dose group. The plasma inflammatory factor levels and oxidative stress indicators malondialdehyde (MDA), glutataione (GSH), and superoxide dismutase (SOD) levels of myocardium, brain, lung, and liver tissues were measured in different groups with hypoxia for 24 h. The degree of histopathological damage of mice was observed with HE staining. The degree of protection of Hemin against tissue hypoxia injury was detected with the hypoxia probe piperidazole. Compared with the blank group, the survival time of mice in the positive drug group, the Hemin medium-dose group, and high-dose group was significantly extended (all P<0.05), with the highest prolongation rate in the Hemin high-dose group. Compared with the hypoxia group, mice in the Hemin high-dose group showed a significant increase in SOD level and GSH content of brain tissue, and a significant decrease in MDA content of lung tissue (all P<0.05). The results of HE staining and hypoxia probe showed that Hemin had a significant protective effect on the damage of liver, heart, brain and lung tissues of mice with hypoxia, and the most obvious effect on that of the brain tissue. Hemin has an effect of improvement on oxidative stress and inflammatory response caused by hypoxia, and has obvious protective effect on tissue damage caused by hypoxia.

The Role of Cydonia oblonga, Portulaca oleracea, and Artemisia dracunculus on Hypoxia

Background: Hypoxia exists in some malignancies and is a prognostic risk factor contributing to tumor growth and metastasis. Anti-hypoxic compounds may improve this situation and be considered as anti-cancer agents. In previous reports, Cydonia oblonga, Portulaca oleracea, and Artemisia dracunculus showed anti-cancer activities. So, we investigated the anti-hypoxic activities of C. oblonga, P. oleracea, and A. dracunculus to evaluate the possible mechanism of their effectiveness in treating cancer. Methods: Total phenolic and flavonoid contents and HPLC analysis were performed on C. oblonga leaves, P. oleracea, and A. dracunculus aerial parts extract. Anti-hypoxic activities were evaluated in asphyctic, haemic, and circulatory hypoxia models. Results: A. dracunculus extract (at 250 mg/kg) significantly improved the survival time compared to the normal saline (P&lt;0.0001) in asphyctic hypoxia, even its effect was significantly better than phenytoin in this dose (P=0.0005). Although the extracts increased the survival time in other doses, their effects were not significant (P&gt;0.05). In haemic hypoxia, the extracts were ineffective at any dose (P&gt;0.05). At 250 mg/kg, P. oleracea and A. dracunculus significantly increased the survival time (P&lt;0.001 and P&lt;0.05, respectively) in circulatory hypoxia. Their effects were similar to propranolol (P&gt;0.05). Conclusion: The anti-cancer effects of C. oblonga are not dependent on the anti-hypoxic effects. P. oleracea and A. dracunculus have anti-hypoxic effects only in high doses, indicating their extracts’ weak anti-hypoxic ability or the presence of potent anti-hypoxic compounds with low concentrations in them.

Peculiarities of paravulvar microcirculation in skin and muscle in blast wound in variants of early local injection of reparative active agent

Introduction. A promising method of correcting microcirculatory disorders in the area of soft tissue injury is the use of agents with antihypoxant action, which include deproteinized calf-blood hemoderivate.The aim of the work was to reveal the peculiarities of subcutaneous and intramuscular local injection of deproteinized calfblood hemoderivate on the changes of microcirculation in the skin and muscles in the experimental blast wound area.Materials and methods. The experiments were performed on 90 male Wistar rats weighing (320±20) g in compliance with international rules of work with laboratory animals. Modeling of an explosive wound of the soft tissues of the femur with mild degree of blood loss was carried out according to the original author’s method (Patent RU No. 2741238 dated 22.01.2021). After primary surgical treatment was performed paravulnarly, deproteinized calf-blood hemoderivate was injected intramuscularly, intramuscularly and subcutaneously (Actovegin drug) once in six points with an insulin syringe. Microcirculation in the skin and muscles of the injured area was assessed by laser Doppler flowmetry using the device LAKK-M (Russia). To determine the normal values of microcirculation, data obtained from healthy animals were used.Results. Local intramuscular injection into the paravular area resulted in an increase of the constant perfusion component (M) by 24.1−35.9 % (p &lt; 0.05) and by 18.0−56.4 % (p &lt; 0.05) in the skin and muscles during all periods of observation, an increase of the variable perfusion component (σ) in the skin by 31.4−38.0 % (p &lt; 0.05) during 28 days and in muscles by 8.8−58.7 % (p &lt; 0.05) during the first 14 days only, increase of Kv ratio in skin by 12.4 % (p = 0.01) early after injury (7 days) and decrease in muscles by 18.3−20.8% (p &lt; 0.05) at 14−28 days. Local combined administration (intramuscularly and subcutaneously) of the drug around the wound promoted the increase of the constant perfusion component (M) in the skin by 23.8 % (p = 0.005) and 6.9 % (p = 0.01) at the 7th and 28th days of observation, increase of σ index in skin by 14.2−45.1 % (p &lt; 0.007) on the 7−14 days and its decrease in muscles by 15.7 % (p = 0.009) by the end of the 7th day of observation in comparison with animals after only intramuscular injection only. Also, the coefficient of variation (Kv) with the combined route of injection was increased in the skin by 8.8−23.8 % (p &lt; 0.009) in the first 14 days and decreased in the muscles by 15.7 % (p = 0.008) in the early period after injury (7 days) relative to its values in animals with intramuscular injection.Discussion. The results of the study allow noting the stimulating effect of deproteinized calf-blood hemoderivate on neovasculogenesis in the damaged tissues, which can be judged by the increase in the constant perfusion component (M). In addition, we can conclude that the direct endothelium-protective effect of the drug consists in the modulation of microcirculatory flow, which confirms the significant increase in the variable perfusion component (σ) throughout the experiment.Conclusion. Local paravular administration of deproteinized calf-blood hemoderivate in experimental blast wound promotes microcirculation increase in the soft tissues of the injury area. Combined (intramuscular and subcutaneous) local paravular injection of the drug allows more effective stimulation of microcirculation in the skin and muscles of the injury area.

A comprehensive review of natural products with anti-hypoxic activity.

Natural products exhibit substantial impacts in the field of anti-hypoxic traetment. Hypoxia can cause altitude sickness and other negative effect on the body. Headache, coma, exhaustion, vomiting and, in severe cases, death are some of the clinical signs. Currently, hypoxia is no longer just a concern in plateau regions; it is also one of the issues that can not be ignored by urban residents. This review covered polysaccharides, alkaloids, saponins, flavonoids, peptides and traditional Chinese compound prescriptions as natural products to protect against hypoxia. The active ingredients, effectiveness and mechanisms were discussed. The related anti-hypoxic mechanisms involve increasing the hemoglobin (HB) content, glycogen content and adenosine triphosphate (ATP) content, removing excessive reactive oxygen species (ROS), reducing lipid peroxidation, regulating the levels of related enzymes in cells, protecting the structural and functional integrity of the mitochondria and regulating the expression of apoptosis-related genes. These comprehensive summaries are beneficial to anti-hypoxic research and provide useful information for the development of anti-hypoxic products.

Elimination profile of the new antihypoxant OKAGERM-4 under normal conditions and confined space hypoxia model

&#x0D; &#x0D; &#x0D; The problem of pharmacological protection of the body from complications of acute hypoxia, which develops in a confined unventilated space, confined space hypoxia (CSH), is relevant and requires immediate solution. Today, in terms of finding new drugs with high antihypoxic potential, the most promising are heterometallic complexes of germanium and 3d-metals (zinc, copper, manganese) with citric and tartaric acids. Toxicometric and screening studies proved high antihypoxic activity and harmlessness of the germanium – manganese (II) tartrate germanate (IV) coordination compound under the laboratory code OKAGERM-4.&#x0D; The aim of the study – to carry out comparative pharmacokinetic analysis of OKAGERM-4 at the stage of its elimination from the central chamber under normal conditions and in the modeled CSH.&#x0D; The experiments were performed on 48 nonlinear white rats of both sexes weighing 170–200 g, divided into two groups: control and experimental (rats in which CSH was modeled by placing them for 25 min in hermetic 10 cm3 sealed containers). In order to determine the pharmacokinetic profile, the level of OKAGERM-4 was determined by germanium content using the colorimetric method in blood serum 45 min, 3 h, 6 h and 24 h after a single intraperitoneal injection to rats at a dose of 96.8 mg/kg.&#x0D; Based on the semi-logarithmic curves obtained, a number of pharmacokinetic parameters were directly calculated, those that characterize the processes of OKAGERM-4 elimination from the central chamber: t1/2β (norm) 0.26 h ± 0.05 h; t1/2β (CSH) 0.23 h ± 0.03 h; K10 (norm) 11.33 h–1 ± 4.90 h–1; K10 (CSH) 11.83 h–1 ± 3.16 h–1; MRT (norm) 1.37 h ± 0.28 h; MRT (CSH) 1.42 h ± 0.18 h; Clt (normal) 7.30 mL/h/kg ± 0.89 mL/h/kg; Clt (CSH) 7.36 mL/h/kg ± 0.55 mL/h/kg.&#x0D; Thus, it has been experimentally established that the process of OKAGERM-4 elimination from the central chamber occurs approximately the same way regardless of the presence of hypoxic damage to the body.&#x0D; &#x0D; &#x0D;

Effects of fullerene C60 with antihypoxants

BACKGROUND: Drug improvement is often carried out with the help of chemical modifications that improve the receptor action or transport of drugs to their target tissues.&#x0D; AIM: The aim of this study was to investigate the effect of combinations of C60 fullerene with amtizol, 2-amino-4-acetylthiazolo[5,4-b]indole, metaprot, metaprot base, and rutin on antihypoxic activities in a model of acute hypoxia with hypercapnia.&#x0D; MATERIALS AND METHODS: Several compounds with mono-, bi-, and tricyclic structures were examined separately or combined with C60 fullerene. All compounds, except for rutin, were synthesized at the Department of Pharmacology of the S.M. Kirov Military Medical Academy and contain active amino groups, nitrogen, and sulfur atoms in the cycles: amtizol (3,5-diamino-1,2,4-thiadiazole), VM-606 (2-amino-4-acetylthiazolo[5,4-b]indole), Metaprot (2-ethylthiobenzimidazole hydrobromide monohydrate), and Metaprot base. All compounds demonstrated antihypoxic activity. Hypobaric hypoxia was simulated in a flow pressure chamber by lifting animals to a height of 10,000 m at a speed of 50 m/s and exposure for 60 min. The preparations were administered intraperitoneally 60 min before the experiment. The protective effect was evaluated by the average life expectancy at altitude. Hypoxia with hypercapnia was assessed on male white mice weighing 2022 g, which were placed in 200 mL glass jars with hermetic lids, which were lowered under water to prevent air leakage. The studied preparations and their complexes with fullerene in the form of a thin suspension with Tween-80 were administered intraperitoneally min before hypoxia. The lifespan of the animals was recorded.&#x0D; RESULTS: The formation of the complex and its properties depend on the development of a donoracceptor bond between the drug and fullerene. An increase in the bioavailability of amtizol in the form of a complex with C60 fullerene increased the antihypoxic activity of the mixture by 40%. For the first time, dynamic curves of the activities of amtizol and 2-amino-4-acetylthiazolo[5,4-b]indole depending on time were obtained in a model of hypercapnic hypoxia.&#x0D; CONCLUSION: Fullerene C60 enhances the antihypoxic activity of the studied compounds due to an increase in the bioavailability of the antihypoxant caused by the microporation of tissue membranes due to the action of fullerene C60.

ИССЛЕДОВАНИЕ ПРОТИВОГИПОКСИЧЕСКОЙ АКТИВНОСТИ НОВОГО СОЕДИНЕНИЯ ЛХТ 3-21 В ЭКСПЕРИМЕНТАХ НА ЖИВОТНЫХ

In experiments with mice under various models of acute hypoxia a new synthesized compound LKhT 3-21 (50 mg/kg) showed a distinct antihypoxic activity. In comparison to mexicor (50 mg/kg), this compound increased lifespan in a hermetic chamber, under hemic hypoxia and histotoxic hypoxia by 107 %, 47 %, and 70 %, respectively. LKhT 3-21 exceeded mexicor in the effect against acute normobaric hypoxia with hypercapnia (in 1.9 times), acute hemic hypoxia (in 1.4 times) and acute histotoxic hypoxia (in 1.6 times).

Evaluation of Antihypoxic Activity of Kojic Acid in Mice

Evaluation of Antihypoxic Activity of Kojic Acid in Mice

ВЛИЯНИЕ МЕТАБОЛИЧЕСКОЙ И ИММУНОКОРРЕГИРУЮЩЕЙ ТЕРАПИИ НА ДИНАМИКУ НАРУШЕННЫХ ПОКАЗАТЕЛЕЙ НЕВРОЛОГИЧЕСКИХ И ПСИХИЧЕСКИХ ФУНКЦИЙ ПРИ ХРОНИЧЕСКОЙ ПРОФЕССИОНАЛЬНОЙ РТУТНОЙ ИНТОКСИКАЦИИ У КОНТИНГЕНТА ИНВАЛИДОВ В ВОЗРАСТЕ 18 ЛЕТ И СТАРШЕ

The use of drugs with antioxidant and antihypoxant activity in combination with immunocorrectors for chronic occupational mercury intoxication in a contingent of disabled people aged 18 years and older makes it possible to increase the effectiveness of medical rehabilitation of this contingent. The developed treatment regimens affect the main links of pathogenetic tissue damage by mercury vapor. In order to increase the objectivity of the results of the study, the predominant neurological disorders occurring in the lower extremities must be diagnosed on a complex computer-dynamic complex "ZEBRIS" with the function of a diagnostic track with a power platform, which allows to identify the degree of distribution of force and pressure of the feet when walking, violations of static support capacity on a moving platform. We have analyzed statistical data on disability due to exposure to chronic mercury intoxication for the period 2019- 2021 in the Republic of Mordovia. Risk groups have been identified according to the degree of loss of professional ability to work, depending on age, duration of work in mercury production, concomitant diseases. Contingents of disabled people with impaired mental and statodynamic functions were identified. Groups of disabled people in need of medical and social rehabilitation measures have been identified.

STUDY OF THE ANTIHYPOXIC EFFICIENCY OF SUCCINATE UNDER THE CONDITIONS OF METHEMOGLOBINEMIA

Modeling of methemoglobinemia (MetHb) led to a violation of antioxidant protection, which was manifested by a decrease in the activity of enzymes of the primary link of the antioxidant system – superoxide dismutase and catalase in blood plasma and brain homogenates of experimental animals. The state of MetHb also led to an increase in the concentration of malondialdehyde, an indicator of lipid peroxidation, as well as an indicator of oxidative modification of proteins. It has been established that the antihypoxic activity in the application of succinic acid significantly suppresses the biochemical changes caused by the hypoxic state.

Antihypoxic Activity of 2,5-diaryl-8,8-dimethyl-3,6,7,8-tetrahydro-2&lt;i&gt;H&lt;/i&gt;-pyrido[4,3,2-&lt;i&gt;de&lt;/i&gt;]quinnolin-3-ones

Introduction. The state of hypoxia, causing damage and cell death, underlies many pathological processes. In addition, hypoxia induces a state of free radical oxidation, which enhances the damaging effect of hypoxic damage. This necessitates the synthesis of new compounds and the creation on their basis of drugs with antihypoxic activity.Aim. The aim of this study is the synthesis and study of the antihypoxic activity of 2,5-diaryl-8,8-dimethyl-3,6,7,8-tetrahydro-2Н-pyrido[4,3,2-de] quinnolin-3-ones.Materials and methods. Compounds of the 2,5-diaryl-8,8-dimethyl-3,6,7,8-tetrahydro-2H-pyrido[4,3,2-de]quinnolin-3-ones series were obtained as a result of the interaction of 2-aryl-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydroquinoline-4-carboxylic acids c o-tolyl-, p-tolyl-, p-fluoro-, p-nitro-, 2,4,6-trichlorophenylhydrazines. As a result, 10 substances were synthesized, the structure of which was confirmed by IR and 1H NMR spectroscopy. The study of the antihypoxic activity of the obtained compounds was carried out using the method of normobaric hypoxia with hypercapnia («hypoxia in a jar»).Results and discussion. The studied compounds have different effects on the lifespan of mice under conditions of acute normobaric hypoxia with hypercapnia. Compounds IIIi and IIId, respectively, increased the lifespan of mice most significantly by 26.36 % and 25.64 %, respectively, compounds IIIa, IIIb, IIIg were less significant, compounds IIIc and IIIf had no effect, and compound IIIj had a prohypoxic effect.Conclusion. Compounds with the most pronounced antihypoxic and antioxidant properties have been identified. Thus, further synthesis and study of 2,5-diaryl-8,8-dimethyl-3,6,7,8-tetrahydro-2H-pyrido[4,3,2-de]cinnolin-3-ones is reasonable.