Succinate Dehydrogenase Activity Research Articles

Respiratory chain dysfunction in perifascicular muscle fibres in patients with dermatomyositis is associated with mitochondrial DNA depletion.

Patients with dermatomyositis (DM) suffer from reduced aerobic metabolism contributing to impaired muscle function, which has been linked to cytochrome c oxidase (COX) deficiency in muscle tissue. This mitochondrial respiratory chain dysfunction is typically seen in perifascicular regions, which also show the most intense inflammatory reaction along with capillary loss and muscle fibre atrophy. The objective of this study was to investigate the pathobiology of the oxidative phosphorylation deficiency in DM. Muscle biopsy specimens with perifascicular COX deficiency from five juveniles and seven adults with DM were investigated. We combined immunohistochemical analyses of subunits in the respiratory chain including complex I (subunit NDUFB8), complex II (succinate dehydrogenase, subunit SDHB) and complex IV (COX, subunit MTCO1) with in situ hybridisation, next generation deep sequencing and quantitative polymerase chain reaction (PCR). There was a profound deficiency of complexes I and IV in the perifascicular regions with enzyme histochemical COX deficiency, whereas succinate dehydrogenase activity and complex II were preserved. In situ hybridisation of mitochondrial RNA showed depletion of mitochondrial DNA (mtDNA) transcripts in the perifascicular regions. Analysis of mtDNA by next generation deep sequencing and quantitative PCR in affected muscle regions showed an overall reduction of mtDNA copy number particularly in the perifascicular regions. The respiratory chain dysfunction in DM muscle is associated with mtDNA depletion causing deficiency of complexes I and IV, which are partially encoded by mtDNA, whereas complex II, which is entirely encoded by nuclear DNA, is preserved. The depletion of mtDNA indicates a perturbed replication of mtDNA explaining the muscle pathology and the disturbed aerobic metabolism.

Protective Effect of Some Essential Oils Against Gamma-Radiation Damages in Tetrahymena pyriformis Exposed to Cobalt-60 Source.

The main purpose of this study was to investigate the protective effect of Rosmarinus officinalis, Origanum compactum, Lavandula angustifolia, and Eucalyptus globulus essential oils (EOs) against gamma-radiation-induced damages on Tetrahymena pyriformis growing in presence of cobalt-60 source. The chemical composition of the 4 EOs was analyzed by gas chromatography-mass spectrometry. The protective effects of EOs on growth, on morphology, and on some metabolic enzymes and antioxidant markers have been evaluated. Thus, addition of EOs significantly improves the growth parameters (generation number and time) in irradiating conditions. All EOs allowed restoring growth parameters over more than 90% compared to the controls. The morphological analysis indicated that T. pyriformis cells growing in irradiating conditions were able to regain their normal form in presence of the different EOs. Our results indicate that the 4 EOs also have protective effects on some metabolic enzymes. They allowed recovering totally or partially the glyceraldehyde 3-phosphate dehydrogenase and the succinate dehydrogenase activities compared to the controls. Moreover, the addition of EOs reduced the lipid peroxidation level and decreased the activities of catalase and superoxide dismutase induced by the gamma-radiation exposure. A more pronounced protective effect was found for O. compactum and L. angustifolia EOs compared to R. officinalis and E. globulus EOs. These results suggest that the studied EOs are efficient natural antioxidants that could offer protection against gamma-radiation-induced damages and can therefore be useful in clinical medicine.

TMS-Like Magnetic Fields Modulate Metabolic Activity of Hepatic and Colorectal Cancer Cells

Transcranial magnetic stimulation (TMS) is a widely available technology employing relatively strong (up to 4 T) pulsed (up to 300 Hz) magnetic fields for diagnostics of brain functions and treatment of various brain disorders. The current paradigm implies that the magnetic induction of Eddy currents in the brain neurons is the leading biological mechanism of TMS. At the same time, it is almost unknown how the TMS-like magnetic fields act on nonneuronal cells. Here, we explored the effects of TMS-like repetitive magnetic stimulation (RMS) on metabolic activity of human colorectal cancer (CRC) and hepatocellular carcinoma (HCC) cells. The HCT116 (CRC) and HuH7 (HCC) <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">in vitro</i> cell cultures were treated using a TMS device “Magstim Rapid <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> ” with an air-cooled “Magstim” figure-eight coil (AFC70). Five intermittent RMS (iRMS) and two burst RMS (bRMS) experimental protocols were applied to the monolayers of the cells as a single treatment session. The activity of succinate dehydrogenase, an enzyme essential for energy production in mitochondria, was measured by 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) colorimetric viability assay in 24 h post-stimulation. Compared to untreated control, in HCT116 cells, a low-frequency iRMS treatment ( <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$f $ </tex-math></inline-formula> = 1 Hz, 600 pulses, <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$B $ </tex-math></inline-formula> = 0.8 T) induced a statistically significant decrease in metabolic activity (viability), while the high-frequency iRMS and bRMS increased it. In HuH7 cells, all tested RMS protocols either did not change or stimulated the metabolic activity (viability) of the cells, in comparison to the untreated control. The analysis of correlations revealed the almost opposite trends in CRC and HCC cells response to the frequency, temporal patterns, and magnetic field flux density considered as the parameters of the experimental RMS. Our findings demonstrate the tumor type- and stimulation protocol-specific effects of the repurposed TMS technology on colorectal and liver cancer cells. The underlying mechanism of these differences requires further study. The current results indicate that TMS-like magnetic fields may have new potential applications as an adjuvant anticancer treatment modality.

Short Communication: Supplementation with calcium butyrate causes an increase in the percentage of oxidative fibers in equine gluteus medius muscle.

Optimal athletic performance requires meeting the energetic demands of the muscle fibers, which are a function of myosin ATPase enzymatic activity. Skeletal muscle with a predominant oxidative metabolism underlies equine athletic success. Sodium butyrate, a short-chain fatty acid, can affect muscle fiber composition in pigs. To determine if a similar scenario exists in horses, 12 adult Thoroughbred geldings (7.4 ± 0.6 yr of age; mean ± SEM) were fed 16 g of calcium butyrate (CB) or an equivalent amount of carrier (CON) daily for 30 d in a crossover design. Middle gluteal muscle biopsies were collected before and after the feeding trial for immunohistochemical determination of fiber type, and RNA and protein isolation. After 30 d, CB increased (P < 0.05) the percentage of type IIA fibers and tended (P = 0.13) to reduce the numbers of type IIX fibers in comparison to control (CON). No changes (P > 0.05) in type I, IIA, or IIX fiber size were observed in response to CB. No differences (P > 0.05) were noted in the abundance of succinate dehydrogenase (SDH) protein or activity between horses receiving CB or CON. Myogenin mRNA abundance was unaffected (P > 0.05) by 30 d of CB supplementation. The increase in type IIA fibers in the absence of altered mitochondrial SDH enzymatic activity suggests that CB affects myosin ATPase expression independent of altered metabolism.

Ultrasonic treatment decreases Lyophyllum decastes fruiting body browning and affects energy metabolism

Lyophyllum decastes is a common mushroom that is prone to browning during prolonged storage. In this study, the effects of ultrasonic treatment on metabolic gene expression, enzyme activity, and metabolic compounds related to L. decastes browning were investigated. Treatment of the fruiting body at 35 kHz and 300 W for 10 min reduced the browning index of L. decastes by 21.0 % and increased the L* value by 11.1 %. Ultrasonic treatment of the fruiting body resulted in higher levels of total phenols, flavonoids, and 9 kinds of amino acid with catalase (CAT) and peroxidase (POD) activities maintained at high levels. Higher cytochrome c oxidase (CCO), succinate dehydrogenase (SDH), phosphofructokinase (PFK), and pyruvate kinase (PK) activities may be ascribed to increased antioxidant capacity. Moreover, ultrasonication retained higher adenosine triphosphate (ATP) concentrations with an increased energy charge, while there were lower levels of adenosine diphosphate (ADP) and reduced and oxidized nicotinamide adenine dinucleotide (NADH and NAD+), respectively. Meanwhile, lower lignin contents were observed, along with retarded polyphenol oxidase (PPO) and lipoxygenase (LOX) activities. Lower PPO activity reduced the fruiting body enzymatic browning rate through decreased expression of LdPpo1, LdPpo2, and LdPpo3 during storage at 4 °C for 16 days. This activity may be used to determine the effectiveness of ultrasonication.

Age-dependent effects of blue light exposure on lifespan, neurodegeneration, and mitochondria physiology in Drosophila melanogaster

Blue light is a predominant component of light emitting devices (LEDs), which are increasingly present in our environment. There is already accumulating evidence that blue light exposure causes damage to retinal cells in vitro and in vivo; however, much less is known about potential effects of blue light on non-retinal cells. That blue light may be detrimental at the organismal level independent from retinal effect was recently shown by findings that it reduces lifespan in worms and also in flies with genetically ablated retinas. Here, we investigated the effects of blue light exposure across the fly lifespan and found that susceptibility to blue light stress is strongly age-dependent. The blue light of the same intensity and duration reduced survival and increased neurodegeneration more significantly in old flies than in young flies. These differences appear to be caused, at least in part, by impairments of mitochondrial respiratory function. We report that blue light significantly reduces the activity of Complex II in the electron transport system and decrease the biochemical activity of succinate dehydrogenase in both young and old flies. In addition, complex I and complex IV activities are reduced by age, as are ATP levels. We therefore propose that older flies are more sensitive to blue light because the light-induced mitochondrial damage potentiates the age-related impairments in energy metabolism that occurs even in darkness. Taken together, our results show that damaging effects of blue light at the organismal level are strongly age dependent and are associated with reduced activity of specific components of energy producing pathways in mitochondria.

Anti-Huntington's Effect of Rosiridin via Oxidative Stress/AchE Inhibition and Modulation of Succinate Dehydrogenase, Nitrite, and BDNF Levels against 3-Nitropropionic Acid in Rodents.

Background: Rosiridin is a compound extracted from Rhodiola sachalinensis; water extracts of Rhodiola root elicit positive effects on the human central nervous system and improve brain function. They are also thought to be beneficial to one’s health, in addition to being antioxidants. The present study aims to evaluate the anti-Huntington’s effect of rosiridin against 3-nitropropionic acid (3-NPA)-induced Huntington’s disease (HD)-like effects in rats. Materials and Methods: The acute toxicity in rats was elucidated to track the conceivable toxicities in the rats. The effectiveness of rosiridin at a dosage of 10 mg/kg was evaluated against several dose administrations of 3-NPA-induced HD-like symptoms in the rats for 22 days. At the end of the study, behavioral parameters were assessed as a hallmark for the cognitive and motor functions in the rats. Similarly, after the behavioral assessment, the animals were sacrificed to obtain a brain tissue homogenate. The prepared homogenate was utilized for the estimation of several biochemical parameters, including oxidative stress (glutathione, catalase, and malondialdehyde), brain-derived neurotrophic factor and succinate dehydrogenase activity, and the glutamate and acetylcholinesterase levels in the brain. Furthermore, inflammatory mediators linked to the occurrence of neuroinflammation in rats were evaluated in the perfused brain tissues. Results: The rosiridin-treated group exhibited a significant restoration of behavioral parameters, including in the beam-walk test, latency in falling during the hanging wire test, and percentage of memory retention during the elevated plus-maze test. Further, rosiridin modulated several biochemical parameters, including oxidative stress, pro-inflammatory activity, brain-derived neurotrophic factor, nitrite, and acetylcholinesterase as compared to disease control group that was treated with 3-NPA. Conclusions: The current study exhibits the anti-Huntington’s effects of rosiridin in experimental animal models.

L-theanine induces skeletal muscle fiber type transformation by activation of prox1/CaN signaling pathway in C2C12 myotubes.

The aim of this study was to investigate the effect and mechanism of L-theanine (LT) on muscle fiber type transformation in C2C12 myotubes. Our data showed that LT exhibited significantly higher slow oxidative muscle fiber expression and lower glycolytic fibers expression. In addition, LT significantly increased the activities of malate dehydrogenase (MDH) and succinic dehydrogenase (SDH), and decreased lactate dehydrogenase (LDH) activity, the calcineurin (CaN) activity and the protein expressions of nuclear factor of activated Tcell 1 (NFATc1), prospero-related homeobox1 (prox1), and calcineurin A (CnA) were significantly increased. However, inhibition of CaN activity by cyclosporine A (CsA) abolished LT-induced increase of slow oxidative muscle fiber expression and decrease of glycolytic fibers expression. Moreover, inhibition of prox1 expression by prox1-siRNA disrupted LT-induced activation of CaN signaling pathway and muscle fiber type transformation. Taken together, these results indicated that LT could promote skeletal muscle fiber type transformation from type II to type I via activation of prox1/CaN signaling pathway.

Fluopyram inhibits tricarboxylic acid cycle but induces γ-aminobutyric acid-shunt pathway to prolong postharvest shelf life of litchi fruit

Rapid pericarp browning results in a short shelf life of postharvest litchi fruit. In this study, the impact of fluopyram (Flu) on litchi pericarp browning and possible mechanisms were investigated. Results showed that application of 0.2 % (v/v) fluopyram (Flu) delayed litchi pericarp browning during storage at 25 °C. Respiration rate and tricarboxylic acid (TCA) cycle were reduced in Flu-treated fruit, as indicated by the decreased succinate dehydrogenase (SDH) and α-ketoglutarate dehydrogenase (α-KGDH) activities. Meanwhile, Flu treatment resulted in higher succinic acid content but lower fumaric acid and α-ketoglutarate contents compared to those in non-Fu-treated fruit. Furthermore, Flu pretreatment maintained higher glutamate (Glu) level via enhancing glutamate dehydrogenase (GDH) activity. Additionally, Flu treatment accelerated gamma-aminobutyric acid (GABA)-shunt pathway by regulating GABA content and activities of glutamate decarboxylase (GAD) as well as GABA transaminase (GABA-T). Importantly, higher ATP and GTP contents were observed in Flu-treated fruit. Taken together, these results suggested that Flu treatment inhibited respiration but accelerated GABA-shunt pathway, which might contribute to higher energy status and thus attenuate litchi pericarp browning. This study provided new insights of Flu application in quality maintenance and shelf life extension of postharvest fruit storage.

Novel soybean peptide iglycin ameliorates insulin resistance of high-fat diet fed C57BL/6J mice and differentiated 3T3L1 adipocytes with improvement of insulin signaling and mitochondrial function

Soy consumption has been associated with potential health benefits in reducing chronic diseases. These physiological functions have been attributed to soy proteins or more commonly to bioactive peptides. Thus, more studies are required to identify these bioactive peptides, and elucidate their biological mechanisms of action. In the present study, a novel peptide iglycin was purified from soybean seeds with a molecular mass of 3.88 kDa. Thereafter, iglycin reduced fasting blood glucose and restored insulin sensitivity of C57BL/6J mice on a high-fat diet with increased phosphorylation of insulin receptor substrate 1 (IRS1) and AKT in adipose tissue. Furthermore, it improved glucose uptake, induced translocation of intracellular GLUT4 to plasma membrane and activation of insulin signaling in adipocytes under insulin-resistant condition. In addition, it decreased reactive oxygen species production, lipid peroxidation and inhibited adipocyte apoptosis with improved mitochondrial function as evidenced by up-regulation of succinate dehydrogenase activity, mitochondrial membrane potential and intracellular ATP store. These data suggested that iglycin ameliorated insulin resistance via activation of insulin signaling, which was associated with inhibition of oxidative stress, adipocyte apoptosis, and improvement of mitochondrial function.

Disruption of O-GlcNAcylation Homeostasis Induced Ovarian Granulosa Cell Injury in Bovine

O-linked β-N-acetylglucosamine (O-GlcNAc) modification is a ubiquitous, reversible, and highly dynamic post-translational modification, which takes charge of almost all biological processes examined. However, little information is available regarding the molecular regulation of O-GlcNAcylation in granulosa cell function and glucose metabolism. This study focused on the impact of disrupted O-GlcNAc cycling on the proliferation and apoptosis of bovine granulosa cells, and further aimed to determine how this influenced glucose metabolism. Pharmacological inhibition of OGT with benzyl-2-acetamido-2-deoxy-α-D-galactopyranoside (BADGP) led to decreased cellular O-GlcNAc levels, as well as OGT and OGA protein expressions, whereas increasing O-GlcNAc levels with the OGA inhibitor, O-(2-acetamido-2-deoxy--gluco-pyranosylidene) (PUGNAc), resulted in elevated OGA protein expression and decreased OGT protein expression in granulosa cells. Dysregulated O-GlcNAc cycling reduced cell viability, downregulated the proliferation-related genes of CDC42 and PCNA transcripts, upregulated the pro-apoptotic genes of BAX and CASPASE-3 mRNA and the ratio of BAX/BCL-2, and increased the apoptotic rate. Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. Moreover, inhibition of OGT significantly increased the expression level of thioredoxin-interacting protein (TXNIP), but repression of OGA had no effect. Collectively, our results suggest that perturbation of O-GlcNAc cycling has a profound effect on granulosa cell function and glucose metabolism.

Starch-based composite coatings modulate cell wall modification and softening in Zaosu pears

Pear fruit is susceptible to softening and pulp disintegration leading to a short postharvest storage life. One possible method to alleviate softening is the use of edible coatings. Starch-based coatings and films were blended with cumin essential oil to investigate the film characteristics and the effect of the coating treatments on enzyme activities of Zaosu pears stored at 25 °C for 28 d. The essential oil incorporation enhanced the color, barrier properties and mechanical stability of the starch films. The coating treatment delayed fruit pulp degradation and retarded the activities of pectin methylesterase (PME), polygalacturonase (PG), cellulase (Cx), β-galactosidase (β-Gal), pectinesterase (PE), and polygalacturonase (PMG), during ambient storage for 28 d. The malondialdehyde (MDA) and membrane permeability (MP) activities of the coated fruits were lower compared to the control fruits. The composite coating improved the antioxidant enzymes; peroxidases (POD), phenylalanine ammonia lyase (PAL), superoxide dismutase (SOD), and catalase (CAT) and induced the fruit resistance against softening. The energy content; adenosine triphosphate (ATP) and energy charge (EC) and the activities of succinic dehydrogenase (SDH) and cytochrome c oxidase (CCO) enzymes were significantly higher in the coated fruits. It is viewed that the use of modified sweet potato starch with 0.2–0.4 % (v/v) cumin essential oil could be a useful tool in postharvest storage of fresh produce.

Properties and mechanism of the antimicrobial peptide APT produced by Lactobacillus ALAC-4

Fungal infection is the huge concerns of crop and food security in the worldwide, promoting the variety of natural antimicrobial agent developments and applications. At present, there has been relatively little research relating to antimicrobial peptide of lactic acid bacteria that inhibits fungi. In this study, the antimicrobial peptide APT produced by Lactobacillus ALAC-4, which was isolated from traditional fermented sour porridge in Inner Mongolia, was focused, and the antimicrobial properties were measured using double-layer plate method. APT performed significant both anti-growth activities against most foodborne microorganisms especially Candida albicans. Candida albicans was used as an indicator strain to detect the antimicrobial activity of APT. The results showed that pores appeared on the cell surface and part of the cell structure remained incomplete, in addition the Candida albicans cell walls were seriously damaged under scanning electron microscope and transmission electron microscope. Concomitantly, soluble total carbohydrate and soluble protein contents increased, and phosphorus consumption, succinate dehydrogenase (SDH) activity and malate dehydrogenase (MDH) activity decreased. It was speculated that APT might contribute towards Candida albicans inhibitions via four potential mechanisms: by damaging cell walls, increasing cell membrane permeability, decreasing phosphonic acid metabolism, and by decreasing the respiratory enzyme activity within Candida albicans.

ПРОЯВИ ОКИСНОГО СТРЕСУ ТА МЕТАБОЛІЧНИХ ПОРУШЕНЬ У DANIO RERIO ЗА ДІЇ ФОСФООРГАНІЧНИХ ПЕСТИЦИДІВ

The aim of this study was to analyze the effects of roundup and malathion in environmentally relevant and subtoxic concentrations on the metabolic processes of zebrafish Danio rerio. Pesticide toxicity was assessed by changes in the activity of enzymes catalase, succinate dehydrogenase, glutathione transferase, glutathione reductase, protein phosphatase and caspase 3.&#x0D; Roundup has been shown to activate catalase, protein phosphatase, and caspase-3, whereas malathion induces caspase 3 only. At the same time, the studied organophosphate pesticides caused a significant decrease in glutathione transferase and succinate dehydrogenase compared to the control, especially under the action of malathion. Moreover, under the influence of malathion there was a decrease in the activity of protein phosphatase and catalase. As for glutathione reductase, the subtoxic concentration of roundup caused its activation, and the ecologically real concentration of malathion caused its inhibition. In sum, malathion caused more noticeable toxic effects in zebrafish than roundup.&#x0D; Therefore, organophosphate pesticides carry significant risks of toxic effects on fish as non-target organisms, which is important to consider when choosing agronomic maintenance options for the harvest and the potential danger to the environment.

The combined effect of acute hypoxic stress and feeding status on the metabolism of yellow catfish (Pelteobagrus fulvidraco)

Metabolism is one of the most important physiological processes in fish that changes daily depending on the variability of disparate factors. Dissolved oxygen and feeding status are critical to the growth and metabolism of fish. In this study, the effects of dissolved oxygen and feeding status, as well as their interaction on the blood biochemistry and metabolism of yellow catfish (Pelteobagrus fulvidraco) were investigated using a two-factor test. At a dissolved oxygen content of 1.2 mg mL−1, yellow catfish were exposed to hypoxia for 48 h and divided into four experimental groups: normoxia (6.5 mg L−1)-fasting group (C; Control group); normoxia-feeding group (F); hypoxia (1.2 mg L−1)-fasting group (H); and hypoxia-feeding group (FH). Analysis revealed that both hypoxia and feeding caused a short-term increase in the number of red blood cells and hemoglobin concentration in yellow catfish, thereby increasing the oxygen-carrying capacity of the blood. After feeding, the metabolic activity in yellow catfish showed a trend of rising and then falling. Following hypoxia, yellow catfish activated anaerobic glycolysis to provide the energy required by the body, and the mode of metabolism in yellow catfish gradually converted from aerobic to anaerobic. Moreover, the activity of respiratory metabolism enzyme succinate dehydrogenase (SDH) tended to decrease and then increase, while that of lactate dehydrogenase (LDH) tended to increase and then decrease, showing opposing trends. Furthermore, the liver glycogen was mobilized, blood glucose levels increased, and lactic acid accumulation occurred in the short term. Meanwhile, the hypoxia-inducible factor (hif-1α) was activated, the expression of glucose metabolism-related genes (epo, hk1, pfkla, pkma, and gk) dramatically increased, and the activities of the three key enzymes involved in glycolysis (HK, PFK, and PK) were elevated for a short period of time. In conclusion, both hypoxia and feeding altered blood biochemical and metabolic responses in yellow catfish over time, and the metabolic responses were more intense in the post-feeding hypoxia group.

ФЕНОМЕН ПРОТИВОЛУЧЕВОЙ ЗАЩИТЫ ИНДРАЛИНОМ КРУПНЫХ ЖИВОТНЫХ (СОБАК) И ЕГО ЭКСТАПОЛЯЦИЯ НА ЧЕЛОВЕКА

Testing the effectiveness of radioprotectors in large animals is an important stage in the introduction of drugs into the practice of medicine. Unique in scale and world practice, comprehensive studies of the radioprotector of emergency action of the drug B-190 (indralin) in experiments on dogs were carried out. Its high radioprotective efficiency was established with gamma, gamma-neutron and proton high energy irradiation. Under gamma irradiation of dogs indralin at an optimal dose of 30 mg/kg had DRF equel 3, the result of which was not recorded in large animals by any of known radioprotectors. It is important that under non-uniform radiation (shielding of abdomen, head or pelvis), protective effect of indralin doubles. The drug is also active in peroral use. Analysis of extrapolation of experimental data on radioprotective properties of indralin from large animals (dogs) to humans on measurement of succinate dehydrogenase (SDH) activity in lymphocytes of peripheral blood is carried out. Activation of SDH during stress response to acute hypoxia, including under the influence of indralin, is associated with the release of adrenaline and noradrenaline. Catecholamines realize their effect through beta-adrenoceptors on lymphocytes. A close correlation was established between the dose and radioprotective effect of indralin and the growth of SDH lymphocyte activity (r = 0.99 p &lt; 0.01). Extrapolation of expected radioprotective effect of indralin per person was carried out according to the formula: DRF = 0.3988e0.009181x[r = 0.995 (0.78–0.9999) p &lt; 0.01], where x is the activity of SDH. DRF of indralin (100 mg intramuscularly) for humans was 1.6. When orally administered indralin at a dose of 450 mg DRF was 1.3.

Skeletal progenitors preserve proliferation and self-renewal upon inhibition of mitochondrial respiration by rerouting the TCA cycle.

SummaryA functional electron transport chain (ETC) is crucial for supporting bioenergetics and biosynthesis. Accordingly, ETC inhibition decreases proliferation in cancer cells but does not seem to impair stem cell proliferation. However, it remains unclear how stem cells metabolically adapt. In this study, we show that pharmacological inhibition of complex III of the ETC in skeletal stem and progenitor cells induces glycolysis side pathways and reroutes the tricarboxylic acid (TCA) cycle to regenerate NAD+ and preserve cell proliferation. These metabolic changes also culminate in increased succinate and 2-hydroxyglutarate levels that inhibit Ten-eleven translocation (TET) DNA demethylase activity, thereby preserving self-renewal and multilineage potential. Mechanistically, mitochondrial malate dehydrogenase and reverse succinate dehydrogenase activity proved to be essential for the metabolic rewiring in response to ETC inhibition. Together, these data show that the metabolic plasticity of skeletal stem and progenitor cells allows them to bypass ETC blockade and preserve their self-renewal.

Features of the reaction of the kidney function of healthy rats to the intake of boric hydrocarbonate sodium mineral waters of varying quantitative macro- and micro-composition

The purpose of the work is a comparative assessment of the effect of boron hydrocarbonate sodium mineral waters with a varying quantitative and qualitative composition of macroelements and with different amounts of a bioactive element on the state of the urinary system of rats. Materials and methods. The work was performed on 81 white rats of the Wistar line of auto bred breeding, weighing 180-200 g. The rats were divided into four groups: group 1 - 21 intact rats served as controls; group 2 - 20 rats treated intragastrically with a soft probe MW "Polyana Ploskivskaya" at a dose of 1% of body weight daily, a course of 7 days; group 3 - 20 rats treated with MW "Polyana Kupel" according to the above method; group 4 - 20 rats treated with MW "Svalyava" according to the above process. Before removing the animals from the experiment, daily urine was collected from them; blood was also taken from the tail vein for biochemical studies. At autopsy, pieces of kidneys were taken for histological and histoenzymological studies (the activity of succinate dehydrogenase and lactate dehydrogenase was determined). Results. The histological studies showed no pathological changes in the kidneys were observed with the use of the studied boron MW. Still, there were structural changes, as well as an increase in the activity of redox enzymes. Changes in kidney function were unidirectional with using any of the investigated MW. Still, they had quantitative differences, which are less related to the amount of boron (in the form of orthoboric acid) in 1 liter of MW and more dependent on the osmolarity of the MW, the qualitative composition of macronutrients, and their ratio. Conclusion. We believe that osmolarity, as an integrated indicator of the state of the macronutrient component of MW, can be used to assess its effect on the structural and functional characteristics of the kidneys.

Sea buckthorn (Hippophae rhamnoides L.) oil exhibits antifungal activity against Aspergillus flavus via disrupting mitochondrial function

The present study sought to examine how sea buckthorn (SBT) oil impacts mitochondrial and overall functionality in Aspergillus flavus. In order to assess the effect of SBT oil, it was used to treat mycelia across a range of concentrations, after which mitochondrial structures were imaged via transmission electron microscopy (TEM). In order to explore the functional impact of this treatment, we additionally examined reactive oxygen species (ROS) production, malondialdehyde (MDA) levels, enzyme activity, and shifts in mitochondrial membrane potential (ΔΨm) following treatment. We found that SBT oil induced mitochondrial damage in A. flavus in a dose-dependent manner, resulting in altered succinate dehydrogenase (SDH) and adenosine triphosphatase (ATPase) activity, reduced ΔΨm levels, and markedly elevated MDA and ROS levels. Together, these findings suggest that SBT oil can mediate antifungal activity against A. flavus through a mechanism associated with its ability to disrupt the tricarboxylic acid (TCA) cycle and mitochondrial potential, leading to MDA and ROS accumulation.

SDH mutations confer complex cross-resistance patterns to SDHIs in Corynespora cassiicola

Succinate dehydrogenase inhibitors (SDHIs) are one of the most frequently used fungicides in cucumber fields in China. Our previous studies indicated that the sensitivity profile of Corynespora cassiicola, the causal agent of Corynespora leaf spot, to different SDHIs varied greatly; however, the underlying mechanism remains unclear. The 50% effective concentration (EC50) values of boscalid, fluopyram, fluxapyroxad and isopyrazam in C. cassiicola collected from 2017 to 2020 shifted, with resistance frequencies of 79.83%, 78.43%, 83.19% and 49.86%, respectively. The sequence alignment of sdhB/C/D of resistant strains revealed that eight single amino acid mutations (B-H278Y/L, B-I280V, C-S73P, C-N75S, C-H134R, D-D95E and D-G109V), and three dual-mutations (B-I280V&C-S73P, B-I280V&C-N75S and C-S73P&C-N75S) conferred various SDHI resistance levels and cross-resistance profiles. The expression level of the sdhB/C/D gene and succinate dehydrogenase (SDH) activity in the mutants were significantly altered by the presence of SDHIs, compared with the wild type strain. Additionally, molecular docking results suggested that the missense mutation influenced the crystal structure of SDH and subsequently interfered with the interaction bonds and bond distances among the target protein and chemicals. In brief, amino acid mutations altered the fungicide response of target gene expression, SDH activity and the binding features of SDH-ligand complexes and subsequently conferred multiple resistance levels and complex cross-resistance patterns to SDHIs in C. cassiicola. The evaluation of C. cassiicola resistance to SDHIs provided a significant foundation for efficient chemical development and integrated CLS management strategies.