Antihypoxic Effect Research Articles

Sodium Hydrosulfide Protects Rats from Hypobaric-Hypoxia-Induced Acute Lung Injury

Hydrogen sulfide (H2S), as a key gas signaling molecule, plays an important role in regulating various diseases, with appropriate concentrations providing antioxidative, anti-inflammatory, and anti-apoptotic effects. The specific role of H2S in acute hypoxic injury remains to be clarified. This study focuses on the H2S donor sodium hydrosulfide (NaHS) and explores its protective effects and mechanisms against acute hypoxic lung injury. First, various mouse hypoxia models were established to evaluate H2S’s protection in hypoxia tolerance. Next, a rat model of acute lung injury (ALI) induced by hypoxia at 6500 m above sea level for 72 h was created to assess H2S’s protective effects and mechanisms. Evaluation metrics included blood gas analysis, blood routine indicators, lung water content, and lung tissue pathology. Additionally, LC-MS/MS and bioinformatic analyses were combined in performing quantitative proteomics on lung tissues from the normoxic control group, the hypoxia model group, and the hypoxia model group with NaHS treatment to preliminarily explore the protective mechanisms of H2S. Further, enzyme-linked immunosorbent assays (ELISA) were used to measure oxidative stress markers and inflammatory factors in rat lung tissues. Lastly, Western blot analysis was performed to detect Nrf2, HO-1, P-NF-κB, NF-κB, HIF-1α, Bcl-2, and Bax proteins in lung tissues. Results showed that H2S exhibited significant anti-hypoxic effects in various hypoxia models, effectively modulating blood gas and blood routine indicators in ALI rats, reducing pulmonary edema, improving lung tissue pathology, and alleviating oxidative stress, inflammatory responses, and apoptosis levels.

CORRECTION OF HEALTH DEVIATIONS CAUSED BY UNFAVORABLE ENVIRONMENTAL CONDITIONS USING NON-PHARMACOLOGICAL MEANS

Lack of atmospheric oxygen (exogenous hypoxia) in residents of high mountain areas leads to functional disturbances of blood circulation, blood composition, activity of tissue respiration enzymes and resulting other biochemical abnormalities, causing a number of diseases. And the open mines operating in these regions create an unfavorable ecological environment, contributing to the deepening of functional disorders of the body among the population. Adolescents in this region are also at risk for the development of pathological processes. These risks can be reduced, and diseases can be prevented using non-drug means, using herbs with antihypoxic effects and special breathing exercises.

Evaluation of Crocetin as a Protective Agent in High Altitude Hypoxia-Induced Organ Damage.

Crocetin is an aglycone of crocin naturally occurring in saffron and has been proved to have antioxidant, anti-inflammatory, and antibacterial activities. In this experiment, the protective effect of crocetin on vital organs in high-altitude hypoxia rats was studied. Crocetin was prepared from gardenia by the alkaline hydrolysis method, and its reducing ability and free radical scavenging ability were tested. The in vitro anti-hypoxia vitality was studied on PC12 cells. The anti-hypoxic survival time of mice was determined in several models. The acute hypoxic injury rat model was established by simulating the hypoxic environment of 8000 m-high altitude for 24 h, and the anti-hypoxia effect of crocetin was evaluated by intraperitoneal injection with the doses of 10, 20, and 40 mg/kg. The water contents of the brain and lung were determined, and the pathological sections in the brain, lung, heart, liver, and kidney were observed by HE staining. The levels of oxidative stress (SOD, CAT, H2O2, GSH, GSH-Px, MDA) and inflammatory factors (IL-1β, IL-6, TNF-α, VEGF) in rat brain, lung, heart, liver, and kidney tissues were detected by ELISA. The results indicated that crocetin exhibited strong reducing ability and free radical scavenging ability and could improve the activity of PC12 cells under hypoxia. After intraperitoneal injection with crocetin, the survival time of mice was prolonged, and the pathological damage, oxidative stress, and inflammation in rats' tissue were ameliorated. The protective activity of crocetin on vital organs in high-altitude hypoxia rats may be related to reducing oxidative stress and inhibiting inflammatory response.

A peptide from yak ameliorates hypoxia-induced kidney injury by inhibiting inflammation and apoptosis via Nrf2 pathway

Chronic kidney disease is a prevalent and severe significant complication of hypoxia. This study found that peptide LVYPFPGPIPN could protect hypoxia-induced renal injury in the animal model. Network pharmacology and molecular docking analysis indicated that cathepsin B (CTSB) and interleukin-1β (IL-1β) represent potential targets for the prevention/treatment of hypoxic-induced renal injury. GO analysis revealed the involvement of these genes in various biological processes, including apoptosis regulation, oxidative stress response, and adaptive immune modulation. Experimental results in vitro and in vivo demonstrated that peptide LVYPFPGPIPN could effectively inhibit apoptosis and stress responses of kidney cells by regulating the NRF2/IL-1β/mitochondrial apoptosis pathway, thereby protecting hypoxic human embryonic kidney cells from damage. The anti-hypoxic effect of the LVYPFPGPIPN offers a novel therapeutic clue for the treatment/prevention of hypoxic-induced kidney injury and inflammation-associated chronic kidney disease.

Characterizing OXPHOS inhibitor-mediated alleviation of hypoxia using high-throughput live cell-imaging

BackgroundHypoxia is a common feature of many solid tumors and causes radiotherapy and immunotherapy resistance. Pharmacological inhibition of oxidative phosphorylation (OXPHOS) has emerged as a therapeutic strategy to reduce hypoxia. However, the OXPHOS inhibitors tested in clinical trials caused only moderate responses in hypoxia alleviation or trials were terminated due to dose-limiting toxicities. To improve the therapeutic benefit, FDA approved OXPHOS inhibitors (e.g. atovaquone) were conjugated to triphenylphosphonium (TPP+) to preferentially target cancer cell’s mitochondria. In this study, we evaluated the hypoxia reducing effects of several mitochondria-targeted OXPHOS inhibitors and compared them to non-mitochondria-targeted OXPHOS inhibitors using newly developed spheroid models for diffusion-limited hypoxia.MethodsB16OVA murine melanoma cells and MC38 murine colon cancer cells expressing a HIF-Responsive Element (HRE)-induced Green Fluorescent Protein (GFP) with an oxygen-dependent degradation domain (HRE-eGFP-ODD) were generated to assess diffusion-limited hypoxia dynamics in spheroids. Spheroids were treated with IACS-010759, atovaquone, metformin, tamoxifen or with mitochondria-targeted atovaquone (Mito-ATO), PEGylated mitochondria-targeted atovaquone (Mito-PEG-ATO) or mitochondria-targeted tamoxifen (MitoTam). Hypoxia dynamics were followed and quantified over time using the IncuCyte Zoom Live Cell-Imaging system.ResultsHypoxic cores developed in B16OVA.HRE and MC38.HRE spheroids within 24 h hours after seeding. Treatment with IACS-010759, metformin, atovaquone, Mito-PEG-ATO and MitoTam showed a dose-dependent reduction of hypoxia in both B16OVA.HRE and MC38.HRE spheroids. Mito-ATO only alleviated hypoxia in MC38.HRE spheroids while tamoxifen was not able to reduce hypoxia in any of the spheroid models. The mitochondria-targeted OXPHOS inhibitors demonstrated stronger anti-hypoxic effects compared to the non-mito-targeted OXPHOS inhibitors.ConclusionsWe successfully developed a high-throughput spheroid model in which hypoxia dynamics can be quantified over time. Using this model, we showed that the mitochondria-targeted OXPHOS inhibitors Mito-ATO, Mito-PEG-ATO and MitoTam reduce hypoxia in tumor cells in a dose-dependent manner, potentially sensitizing hypoxic tumor cells for radiotherapy.

Evaluation of antihypoxic effects of therapeutic breathing mixtures with high argon content on the example of acute blood loss in laboratory animals: a preclinical randomized experimental study

Background. According to the hypothesis of the study, the therapeutic efficacy of measures to treat hypoxic (ischemic) emergencies can be significantly increased by using an artificial gas mixture with normal or increased oxygen content and a high content of argon, being bioactive despite its chemical inertness.Objective. To experimentally evaluate the antihypoxic effects of argon on the example of acute massive blood loss in experimental animals.Methods. The study was carried out on 72 albino male gray rats with a baseline body weight of 220–250 g. The experiments were performed at the premises of the Konstantinov St. Petersburg Nuclear Physics Institute of the Kurchatov Institute and the Smorodintsev Research Institute of Influenza (Russia). Prior to the experiment, the animals were quarantined for 2 weeks in the vivariums of the performing organizations. Acute massive blood loss in rats was formed by taking blood (12 ± 1% of body weight on average) using syringe method by transcutaneous cardiac puncture. Rats were randomized into 3 groups (24 individuals each) depending on the gaseous medium where the animal was placed after artificial blood loss. Composition of the applied gaseous medium in the comparison groups: medium No. 1 — oxygen 21% vol.; argon — 30% vol.; nitrogen — the rest; medium No. 2 — oxygen 21% vol.; argon — the rest; medium No. 3 (control) — air. The postoperative follow-up (post-conditioning) for 8 hours involved assessing and recording the following indicators: survival/lethality rates; recovery rates (anesthesia recovery, somatic mobilization); clinical symptoms of possible intoxication with the gas mixture during inhalation exposure. The surviving animals were then monitored for 4 days to evaluate their health and behavioral performance. Upon completing the observation period, the animals were euthanized.Results. After artificially-induced blood loss, all the non-survivors died within 1.5–8 hours after the operation. In group 1 (post-conditioning in medium No. 1), the lethality of laboratory animals amounted to 4 individuals out of 24 (16%); in group 2 (post-conditioning in medium No. 2) — 2 individuals out of 24 (8%). In the control group, the lethality rate was significantly higher — 10 animals out of 24 (42%). The surviving animals demonstrated no lethality or morbidity within 4 days after the exposure. Analysis of outcomes between experimental groups and controls revealed that the significance of differences in the lethality index between group 1 and control (by Fisher’s two-sided criterion) comprised p = 0.06; between group 2 and control — p = 0.017. When the statistical “power” of the experimental group was increased (by combining samples 1 and 2), the significance of differences in outcomes in this group compared to the control accounted for p < 0.001.Conclusion. The conducted studies confirmed the hypothesis about the pronounced antihypoxic effect of argon, which significantly increased the survival rate of experimental animals after massive artificially-induced blood loss.

The hypothermic effect of the antihypoxant 2-aminobenztiazole

BACKGROUND: One of the compounds studied at the Department of Pharmacology of the Kirov Military Medical Academy is a compound with a proven antihypoxic effect of 2-aminobenzothiazole (2-ABT). The mechanism of action of this substance is partially associated with the central action, and its protective effect may potentially be due to the general hypothermic effect.
 AIM: To determine the effect of 2-ABT on body temperature.
 MATERIALS AND METHODS: Experiments were carried out on 24 adult males of white outbred mice. 2-ABT was previously dissolved in 0.9% sodium chloride solution and administered intraperitoneally to mice at doses of 32.5 mg/kg (with proven antihypoxic effect), 21.7 mg/kg or 10.8 mg/kg. Rectal temperature was measured with an electronic thermometer DT-623 (China) before administration of the test substance, as well as 5, 30 and 60 minutes after the injection.RESULTS: Compound 2-ABT has a pronounced dose-dependent hypothermic effect. This effect is maximally expressed in a dose in which the compound has a proven antihypoxic property – 32.5 mg/kg. The hypothermic effect manifests itself within 5 minutes after administration, the maximum decrease in body temperature is observed after 30 minutes, while the effect persists for an hour.
 CONCLUSION: 2-ABT may be a promising compound for the creation of a drug for drug-induced (controlled) hypothermia.

Antihypoxic effect of almid-containing metal-complex compounds in the experiment

BACKGROUND: To increase resistance to hypoxia, various methods of hypoxic training, mental effects, and use of pharmacological antihypoxants are employed.
 AIM: To test new metal-complex compounds containing the antihypoxant almid in mice under conditions of acute hypoxia to determine their protective properties.
 MATERIALS AND METHODS: In the first stage of the study, four new metal-complex compounds of magnesium, calcium, titanium, and vanadium containing the antihypoxant almid were screened in experiments on mice (n = 550) under acute hypoxic conditions with hypercapnia. The antihypoxants almid and amtizole were used as comparison substances. Acute hypoxia was induced by placing the animals in pharmacy glasses with a volume of 0.25 L with closed lapped stoppers. The substances were administered intraperitoneally at doses of 25, 50, and 100 mg/kg previously dissolved in 0.3 mL of NaCl solution. The incubation period was 60 min. The antihypoxic effect was considered confirmed if the lifespan increased by ≥20%. “Lifespan” refers to the time interval from the moment the mice were placed in a pharmacy glass to the development of the first agonal inhalation, after which the animals were quickly removed to preserve life. The rectal temperature of the animals was measured before the introduction of substances, immediately before being exposed to acute hypoxic conditions with hypercapnia, and after removal. Twenty-four hours after the first stage of the experiment, mice of the control group and mice that proved their ability to resist acute hypoxia with hypercapnia were repeatedly exposed to acute hypoxic conditions with hypercapnia after the use of substances.
 RESULTS: A distinct antihypoxic effect exceeding the effectiveness of the comparison substances was obtained only in one substance—πQ2460 with titanium as a metal-complexing agent—and a ligand in the form of fumaric acid. After the administration of πQ2460, a dose-dependent decrease in rectal temperature was observed in mice. The lifespan of animals increased with an increase in the dosage of πQ2460, i.e., by 43.9%, 103.1%, and 152.8% for doses of 25, 50, and 100 mg/kg, respectively. The results of the second stage of the experiment confirmed the stable protective effect of πQ2460 but with an equalization of the effect of the studied doses, which increased the lifespan under acute hypoxic conditions with hypercapnia to an average of 60–70 min (control group, 40.5 min).
 CONCLUSION: Among the compounds containing the antihypoxant almid in the complex molecule, πQ2460 (metal, titanium; ligand, fumaric acid) was found to have a stable protective dose-dependent effect on the development of acute hypoxia with hypercapnia in mice exceeding that for almid and the reference antihypoxant amtizole. The antihypoxic effect of πQ2460 persisted 24 h after its administration but leveled off for the studied doses—25, 50, and 100 mg/kg. Considering the data obtained during the comparison of the indicators of resistance to acute hypoxia in the control group, a hypothesis was proposed regarding the possibility of forming a preconditioning effect in animals from the primary effects of acute hypoxia.

Creator of the concept of antihypoxants and actoprotectors: On the occasion of the 100th anniversary of Professor V.M. Vinogradov

Vasiliy M. Vinogradov (1924–2003) and his scientific school are famous for their creation and study of two fundamental new classes of pharmacological drugs, promising for military medicine, medicine for disasters and extreme conditions, and for civilian healthcare. This refers to the development of antihypoxants, which are drugs that protect the body when there is a lack of oxygen in the cells or disturbances in its utilization, and actoprotectors (from the Latin “actus” — movement), which are drugs of a nondepleting type of action that increase and maintain the physical performance of the body in unfavorable conditions. At the Department of Pharmacology of the Military Medical Academy in the 1960s, F.Yu. Rachinsky synthesized the first highly effective antihypoxants structurally related to aliphatic and cyclic aminothiols — gutimin, amtizole, bemitil, almid, and etomerzole. Hypoxia is the most common, everyday factor in resuscitation practice; however, it is not the only factor causing energy deficiency with severe, often dramatic consequences for cells, organs, and the body as a whole. Therefore, when we talk about antihypoxants, we are referring to drugs that can smooth out this deficiency using various mechanisms, protect cells at the reversible stage of their damage, and activate the formation of structure and functions. These drugs were subjected to a detailed pharmacological study, and a key link in their mechanism of action was identified — normalization of energy metabolism when there is a lack of oxygen in cells or disturbances in their use. All aliphatic and cyclic aminothiols (gutimin, amtizole, bemitil, almid, etomerzol, and many of their analogs) have three main types of activity, which are expressed differently in each of the drugs, which makes it possible to profile their use in different clinical situations and in healthy people. These include (1) antihypoxic effects, (2) antioxidant effects, and (3) ability to accelerate the repair and adaptive synthesis of RNA, enzymes, and functional and structural proteins under various types of damage, such as hypoxic, infectious, toxic, and stress, and in adaptation to complicated conditions. All these directions were not only evaluated experimentally but also confirmed in practice. This article examines various aspects of antihypoxic drugs synthesized and studied at the Department of Pharmacology of the S.M. Kirov Military Medical Academy for the last 60 years.

Biological Properties of Cyclohex-3-Encarbonyl Acid Pyridin-2-Yl Amide Compound

The synthesized carboxyamide compound was obtained by the reaction of cyclohex-3-ene carbonic acid chloroanhydride with 2-aminopyridine. The biologically active property of this compound has been studied. Based on the experience in the pharmacology department, it was determined that the carboxyamide compound can be used as a drug. The experiment was conducted on animals in the laboratory and how those substances affect the cell was studied. Substances can cause certain changes in the body only when they react with the cells of the body and combine with them; for this, the structure of their molecules must be specific. Not only the composition of the molecules, but also all the structural details, including the distribution of their charges and the location of their functional groups, are of great importance. The general structure of molecules of physiologically active substances should correspond to the structure of specific molecules of cells. As a result of biological research, it was determined that this substance has a calming effect on the nervous system, eliminates muscle spasms. It has myorelaxation and antihypoxia properties. Myorelaxation in animals strengthens skeletal muscles. And the antihypoxia effect doubles the duration of life in animals.

Establishment of microneurovascular units in alginate hydrogel microspheres to reveal the anti-hypoxic effect of salidroside

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Rhodiola crenulata alleviates hypobaric hypoxia-induced brain injury by maintaining BBB integrity and balancing energy metabolism dysfunction

Background/Purpose: Rhodiola crenulata (Hook. f. et Thoms.) H. Ohba (R. crenulate), a famous and characteristic Tibetan medicine, has been demonstrated to exert an outstanding brain protection role in the treatment of high-altitude hypoxia disease. However, the metabolic effects of R. crenulate on high-altitude hypoxic brain injury (HHBI) are still incompletely understood. Herein, the anti-hypoxic effect and associated mechanisms of R. crenulate were explored through both in vivo and in vitro experiments. Study design/MethodsThe mice model of HHBI was established using an animal hypobaric and hypoxic chamber. R. crenulate extract (RCE, 0.5, 1.0 and 2.0 g/kg) and salidroside (Sal, 25, 50 and 100 mg/kg) was given by gavage for 7 days. Pathological changes and neuronal apoptosis of mice hippocampus and cortex were evaluated using H&E and TUNEL staining, respectively. The effects of RCE and Sal on the permeability of blood brain barrier (BBB) were detected by Evans blue staining and NIR-II fluorescence imaging. Meanwhile, the ultrastructural BBB and cerebrovascular damages were observed using a transmission electron microscope (TEM). The levels of tight junction proteins Claudin-1, ZO-1 and occludin were detected by immunofluorescence. Additionally, the metabolites in mice serum and brain were determined using UHPLC-MS and MALDI-MSI analysis. The cell viability of Sal on hypoxic HT22 cells induced by CoCl2 was investigated by cell counting kit-8. The contents of LDH, MDA, SOD, GSH-PX and SDH were detected by using commercial biochemical kits. Meanwhile, intracellular ROS, Ca2+ and mitochondrial membrane potential were determined by corresponding specific labeled probes. The intracellular metabolites of HT22 cells were performed by the targeted metabolomics analysis of the Q300 kit. The cell apoptosis and necrosis were examined by YO-PRO-1/PI, Annexin V/PI and TUNEL staining. In addition, mitochondrial morphology was tested by Mito-tracker red with confocal microscopy and TEM. Real-time ATP production, oxygen consumption rate, and proton efflux rate were measured using a Seahorse analyzer. Subsequently, MCU, OPA1, p-Drp1ser616, p-AMPKα, p-AMPKβ and Sirt1 were determined by immunofluorescent and western blot analyses. ResultsThe results demonstrated that R. crenulate and Sal exert anti-hypoxic brain protection from inhibiting neuronal apoptosis, maintaining BBB integrity, increasing tight junction protein Claudin-1, ZO-1 and occludin and improving mitochondrial morphology and function. Mechanistically, R. crenulate and Sal alleviated HHBI by enhancing the tricarboxylic acid cycle to meet the demand of energy of brain. Additionally, experiments in vitro confirmed that Sal could ameliorate the apoptosis of HT22 cells, improve mitochondrial morphology and energy metabolism by enhancing mitochondrial respiration and glycolysis. Meanwhile, Sal-mediated MCU inhibited the activation of Drp1 and enhanced the expression of OPA1 to maintain mitochondrial homeostasis, as well as activation of AMPK and Sirt1 to enhance ATP production. ConclusionCollectively, the findings suggested that RCE and Sal may afford a protective intervention in HHBI through maintaining BBB integrity and improving energy metabolism via balancing MCU-mediated mitochondrial homeostasis by activating the AMPK/Sirt1 signaling pathway.

Mexidol, Cytoflavin, and succinic acid derivatives as antihypoxic, anti-ischemic metabolic modulators, and ergogenic aids in athletes and consideration of their potential as performance enhancing drugs.

Emoxypine (ethylmethylhydroxypyridine) is a synthetic derivative of vitamin B6 . Emoxypine succinate is a registered drug in Russia and Ukraine under various trade names including Mexidol, Mexicor, and Armadin Long. Mexidol demonstrates antihypoxic and anti-ischemic effects and also modulates metabolism. The use of Mexidol by Russian athletes has been confirmed in the past. Current use by athletes is unknown as this drug is not monitored or included in drug testing protocol. Metabotropic and antihypoxic effects of Mexidol were compared to the effects of meldonium or trimetazidine, both of which are included on the World Anti-Doping Agency (WADA) Prohibited List in category S4.4. Metabolic Modulators. The conjugation of emoxypine with succinate elevates the therapeutic effectiveness of the Mexidol formulation as succinic acid itself has important impacts to consider despite being a common food additive and drug excipient. Other succinic acid salts like ammonium succinate, found as dietary supplement, have been patented as performance enhancers. Available research on healthy subjects suggests that combinations of selected 3-substituted pyridine derivatives with succinate including Mexidol and a related drug Cytoflavin can enhance the performance of athletes. Cytoflavin is a multi-component formula containing meglumine sodium succinate, nicotinamide (vitamin B3 ), inosine (riboxin), and riboflavin. Other related succinate-based drugs include Remaxol, Reamberin, and Cogitum. Mexidol and Cytoflavin and related substances exhibit similar biological effects as drugs on the WADA Prohibited List, and if they are used for performance enhancement by athletes, they could be worthy of consideration as prohibited substances in sport.

РОЛЬ ОЗОНА В АДАПТИВНЫХ ИЗМЕНЕНИЯХ ЭРИТРОЦИТАРНОГО ЗВЕНА

The analysis of literature and our own data on the study of the mechanisms of the physiological action of ozone on the erythrocyte link of the blood was carried out. The present article discusses the effect of ozone on the oxygenbinding capacity of blood and its pro-oxidant-antioxidant balance. The effect of this gas manifests itself in different ways under conditions of changing activity of the system of gas transmitters (nitrogen monoxide and hydrogen sulfide) and at different values of the partial pressure of oxygen and carbon dioxide. The antihypoxic effect of ozone is provided with the participation of gas transmitters that realize their action through intraerythrocytic mechanisms of formation of hemoglobin affinity for oxygen, which justifies its use as a means of improving the adaptive and antihypoxic capabilities of the body.

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<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>0.05). In haemic hypoxia, the extracts were ineffective at any dose (P>0.05). At 250 mg/kg, P. oleracea and A. dracunculus significantly increased the survival time (P<0.001 and P<0.05, respectively) in circulatory hypoxia. Their effects were similar to propranolol (P>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.

Substantiation of the Combined Use of Negative Pressure Therapy and Meglumine Sodium Succinate in the Treatment of Wounds of Various Etiologies

The review presents a theoretical rationale for the effectiveness of including topically NPWT therapy and meglumine sodium succinate intravenously in the complex therapy of wounds of various etiologies. The biochemical pathways accompanying the formation of normoxia and hypoxia of varying severity, the significance of succinate in their formation, including depending on the form of its intake into the body (exogenous and endogenous pathways), are given. Thus, when endogenous production of succinic acid is decompensated, the tricarboxylic acid cycle is inhibited and anaerobic glycolysis is activated. At this moment and before the onset of irreversible biochemical damage, the restoration of energy exchange processes begins to depend on succinate, including its exogenous intake. Additional, but no less important, antihypoxic effects of exogenous succinate include stimulation of succinate oxidase oxidation of succinic acid with the restoration of its consumption in the mitochondrial respiratory chain and an increase in the activity of the antioxidant function of glutathione, as well as stimulation of protein metabolism. Reamberin (meglumine sodium succinate) significantly accelerates tissue recovery during hypoxia due to its antihypoxic, cytoprotective and other effects due to the activation of HIF-1ɑ biologically active factors.

Metformin Reduces Bone Resorption in Apical Periodontitis Through Regulation of Osteoblast and Osteoclast Differentiation

IntroductionWe have previously demonstrated that auxiliary metformin therapy promotes healing of apical periodontitis. Here we aimed to investigate the effects of metformin on osteoblast differentiation and osteoclast formation in cultured cells and rat apical periodontitis. MethodsMurine pre-osteoblasts MC3T3-E1 and macrophages RAW264.7 were cultured under hypoxia (2% oxygen) or normoxia (21% oxygen) and stimulated with receptor activator of nuclear factor-κB ligand (RANKL) when indicated. Metformin was added to the cultures to evaluate its anti-hypoxic effects. Expressions of osteoblast differentiation regulator runt-related transcription factor 2 (RUNX2), RANKL, and osteoclast marker tartrate-resistant acid phosphatase (TRAP) were assessed by Western blot. Apical periodontitis was induced in mandibular first molars of 10 Sprague-Dawley rats. Root canal therapy with or without metformin supplement was performed. Periapical bone resorption was measured by micro-computed tomography. Immunohistochemistry was used to examine RUNX2, RANKL, and TRAP expressions. ResultsHypoxia suppressed RUNX2 expression and enhanced RANKL synthesis in pre-osteoblasts. TRAP production increased in macrophages after hypoxia and/or RANKL stimulation. Metformin reversed hypoxia-induced RUNX2 suppression and RANKL synthesis in pre-osteoblasts. Metformin also inhibited hypoxia and RANKL-enhanced TRAP synthesis in macrophages. Intracanal metformin diminished bone loss in rat apical periodontitis. Comparing with vehicle control, cells lining bone surfaces in metformin-treated lesions had significantly stronger expression of RUNX2 and decreased synthesis of RANKL and TRAP. ConclusionsAlleviation of bone resorption by intracanal metformin was associated with enhanced osteoblast differentiation and diminished osteoclast formation in rat apical periodontitis. Our results endorsed the role of metformin as an effective medicament for inflammatory bone diseases.

Study into the Efficacy of the Epophen Substance in Normobaric Hypoxia

Hypoxia is associated with reduced oxygen levels in the body, individual organs, or tissues. Hypoxia is the most common cause of cell damage, emerging under a lack of oxygen in the inhaled air, blood (hypoxemia), or tissues (violations of tissue respiration). When the strength or duration of hypoxic exposure exceeds the adaptive capabilities of the body, an organ, or a tissue, irreversible changes may develop. Resistance to hypoxia can be enhanced by pharmacological agents that improve oxygen delivery and/or the effectiveness of its use. This study was conducted to determine the antihypoxic effect of the Epophen drug. Epophen was found to exhibit a pronounced antihypoxic effect, with the efficacy varying from 24 to 89% depending on the drug dose and hypoxia type.

Synthesis, Toxicological Evaluation, and Antihypoxic Effect of 2-Ethyl-6-Methylpyridinol-3-yl Thioctate

Synthesis, Toxicological Evaluation, and Antihypoxic Effect of 2-Ethyl-6-Methylpyridinol-3-yl Thioctate

Non-Alcoholic Functional Drinks Containing Natural Raw Materials

The purpose of research was comprehensive research to clarify the feasibility and possibility of using non-traditional raw materials and metal complexes in functional food products.The realization of the possibilities of using collagen base in food products as a carrier of biologically active substances is of great interest. The joint use of collagen in the design of functional products with components of plant raw materials and biocomplexes seems rational for people suffering from a deficiency of minerals, dietary fiber, vitamins, etc. and contributes to an increase in shelf life.Methods. The objects of the study were: succinic, ascorbic and nicotinic acids; biologically active medicinal substances; salts of 3D-metals, coordination compounds of metals; extracts of St. John's wort herb (Hyperici herba), inflorescences of marigolds prostrate (Tagets patula L), Calendula officinalis and fruits of common cherry (Prúnus pádus). Compositions of functional soft drinks with collagen.Results. It has been established that biocomplexes have pronounced antimicrobial and anti-inflammatory activity, exhibit an antihypoxic effect comparable to comparison drugs in collagen-based polymer systems, which opens up broad prospects for their use as biologically active compounds in the food industry. One of the objectives of the study was to develop the composition and technology for producing a functional jelly-like drink using biocomplexes and herbal medicinal raw materials, which made it possible to obtain soft drinks with a high content of biologically active substances: esters, minerals, trace elements, alkaloids, biogenic amines and other biologically active substances.Conclusion. Drinks with high organoleptic characteristics that persist for a long time, high nutritional and biological value and reduced contamination, contributing to the improvement of metabolic processes, were obtained. The proposed soft drinks can be recommended for dietary and therapeutic and preventive nutrition to various groups of people suffering from a deficiency of minerals, dietary fiber, which manifests itself in diseases of the digestive and musculoskeletal systems, violation of human cardiovascular functions.