Synthetic Activity Research Articles

Abstract P3016: Pathologic Matrix Markers Are Differentially Modulated By VSMC-Specific SGK-1 Activity In Hypertension And Abdominal Aortic Aneurysm

Introduction: The VSMC switch to synthetic phenotype promotes aortic pathology such as hypertension (HTN) and abdominal aortic aneurysm (AAA). Mechanical activation of serum and glucocorticoid inducible kinase-1 (SGK-1) alters the VSMC synthetic profile to promote remodeling. Plasma biomarkers may represent opportunities to assess VSMC function in aortic disease, and we hypothesize that analysis of a panel of plasma pathologic matrix markers (PMM) representing synthetic VSMC phenotype can reflect SGK-1-dependent activity. Methods: HTN was induced in wild-type C57Bl/6 (WT) and smooth muscle cell specific SGK-1 knockout (SMC-SGK-1KO +/- ) mice with AngiotensinII infusion (1.46mg/kg/day, n=4-6). Separate mice underwent AAA induction by peri-adventitial CaCl 2 application (n=4-6). Terminal procedure included collecting systolic blood pressure (SBP), aortic diameter (AoD), and plasma. ELISA for PMMs included Interleukin-6 (IL-6), Matrix Metalloproteinase-9 (MMP-9), Cathepsin S (CtsS), and Cystatin C (CysC), Osteoprotegerin (OPG), and Tenascin C (TNC). Impact of the panel was evaluated by a composite T-score. Statistics included T-test and ANOVA. Results: WT+HTN had >30% increased SBP and elevation of IL-6, CtsS, CysC, and TNC (p<0.05). SMC-SGK-1KO +/- +HTN had equally elevated SBP, but no change in PMMs, suggesting that SGK-1 contributed to HTN-induced VSMC synthetic activity. WT+AAA had >65% increased AoD and elevation of all PMMs (p<0.05). Alternatively, SMC-SGK-1KO +/- +AAA had abrogated growth (29.4 + 3.6%, p<0.05 vs WT and WT+AAA) with IL-6, CtsS, CysC, and TNC returning to baseline, suggesting that SGK-1-dependent production of these PMMS was necessary for true AAA growth. Composite T-scores differed between Control, HTN, and AAA in WT mice (0.78 + 0.08 vs 2.91 + 0.29 vs 7.11 + 0.71 respectively, p<0.05). In SMC-SGK-1KO +/- mice, T-score normalized in HTN but remained elevated in AAA (2.19 + 0.21, p<0.05 vs Control and WT+AAA), attributable to the elevations in MMP-9 and OPG, peptides produced by inflammatory infiltrate. Conclusion: A panel of PMMs can be scored to reflect synthetic activity of VSMCs in aortic pathology, as well as response to inhibition, and warrants further investigation for the clinical care of patients with vascular disease.

Association of mutation in the mtDNA CytB gene with macrophage proliferation and synthetic activity

Association of mutation in the mtDNA CytB gene with macrophage proliferation and synthetic activity

Polymer Cu2+ and Ag+ furancarboxylate complexes with 4,4’-bipyridine: synthetic approaches, structure, thermal behavior, and biological activity

Polymer Cu2+ and Ag+ furancarboxylate complexes with 4,4’-bipyridine: synthetic approaches, structure, thermal behavior, and biological activity

Potential of nanoemulsions for accelerated wound healing: innovative strategies.

Wounds represent various significant health concerns for patients and also contribute major costs to healthcare systems. Wound healing comprises of overlapped and various coordinated steps such as homeostasis, inflammation, proliferation, and remodelling. In response to the failure of many strategies in delivering intended results including wound closure, fluid loss control, and exhibiting properties such as durability, targeted delivery, accelerated action, along with histocompatibility, numerous nanotechnological advances have been introduced. To understand the magnitude of wound therapy, this systematic and updated review discussing the effectiveness of nanoemulsions has been undertaken. This review portrays mechanisms associated with wound healing, factors for delayed wound healing and various technologies utilized to treat wounds effectively. While many strategies are available, nanoemulsions have attracted tremendous attention of scientists globally for the research in wound therapy due to their long-term thermodynamic stability and bioavailability. Nanoemulsions not only aid in tissue repair, but also considered as an excellent delivery system for various synthetic and natural actives. Nanotechnology provides several pivotal benefits in wound healing, including improved skin permeation, controlled release and stimulation of fibroblast cell proliferation. Significant role of nanoemulsions in improved wound healing along with their preparation techniques has also been highlighted with special emphasis on mechanistic insights. This article illustrates recent research advancements for the utilization of nanoemulsions in wound treatment. Adequate literature search has been conducted using keywords "Nanoemulsions in wound healing", "Wound therapy and nanoemulsions", "Herbal actives in wound therapy", Natural oils and wounds treatment" etc. from PubMed, Science Direct and Google Scholar databases. Referred and original publications in the English language accessed till April 2022 has been included, whereas non-English language papers, unpublished data and non-original papers were excluded from the study.

Multidisciplinary Studies of the Thyroid Gland’s Synthetic Activity under Conditions of Iodine Deficiency Using Correlation Analysis

The article examines the results of a multidisciplinary study of the thyroid follicular cells’ synthetic activity of male albino rats using the author’s methods for determining the profiles of hormonopoietic cells’ special capacities and semi-quantitative analysis of electronograms, a package of mathematical methods using the principle of fuzzy logic, the cluster approach to grouping data, the principle of phase interval, correlation analysis using Pearson’s formula and evaluating the results according to the Chaddock scale, interpreting the obtained results from the standpoint of cytophysiology. A comparative study on the effect of low, moderate, and high doses of organic and inorganic iodine on changes in correlations between protein-synthesizing organelles of follicular cells under conditions of dietary iodine deficiency was carried out. Based on the data on the number, strength and direction of correlations, a comparative study on the effect of low, moderate, and high doses of organic and inorganic iodine on the thyroid follicular cells’ protein-synthesizing organelles under conditions of dietary iodine deficiency was carried out. The information on the peculiarities of thyroid hormonopoiesis under the action of iodine of different chemical nature was deepened and the greater activating effect of organic iodine was proved, which is of scientific interest and has practical significance for the development of personalized preventive measures for dietary iodine deficiency.

Heterocyclic Iminoquinones and Quinones from the National Cancer Institute (NCI, USA) COMPARE Analysis.

This review uses the National Cancer Institute (NCI) COMPARE program to establish an extensive list of heterocyclic iminoquinones and quinones with similarities in differential growth inhibition patterns across the 60-cell line panel of the NCI Developmental Therapeutics Program (DTP). Many natural products and synthetic analogues are revealed as potential NAD(P)H:quinone oxidoreductase 1 (NQO1) substrates, through correlations to dipyridoimidazo[5,4-f]benzimidazoleiminoquinone (DPIQ), and as potential thioredoxin reductase (TrxR) inhibitors, through correlations to benzo[1,2,4]triazin-7-ones and pleurotin. The strong correlation to NQO1 infers the enzyme has a major influence on the amount of the active compound with benzo[e]perimidines, phenoxazinones, benz[f]pyrido[1,2-a]indole-6,11-quinones, seriniquinones, kalasinamide, indolequinones, and furano[2,3-b]naphthoquinones, hypothesised as prodrugs. Compounds with very strong correlations to known TrxR inhibitors had inverse correlations to the expression of both reductase enzymes, NQO1 and TrxR, including naphtho[2,3-b][1,4]oxazepane-6,11-diones, benzo[a]carbazole-1,4-diones, pyranonaphthoquinones (including kalafungin, nanaomycin A, and analogues of griseusin A), and discorhabdin C. Quinoline-5,8-dione scaffolds based on streptonigrin and lavendamycin can correlate to either reductase. Inhibitors of TrxR are not necessarily (imino)quinones, e.g., parthenolides, while oxidising moieties are essential for correlations to NQO1, as with the mitosenes. Herein, an overview of synthetic methods and biological activity of each family of heterocyclic imino(quinone) is provided.

4-Thiazolidinones: A structural motif of great synthetic and biological activities

4-Thiazolidinones: A structural motif of great synthetic and biological activities

Analysis of Synthetic Notch activation in Clonal Cell Populations in the Fly Wing Using Different Promoters

Analysis of Synthetic Notch activation in Clonal Cell Populations in the Fly Wing Using Different Promoters

Insecticidal and repellent activities of Azadirachta indica A. (Juss) oil against fifth instar larvae and adults of Sahlbergella singularis (Hemiptera:Miridae)

Sahlbergella singularis is one of the insects that causes the most damage to cocoa trees in Togo. The management of this pest is mainly based on chemical control, with its negative consequences for human health and the environment. In order to find an alternative to the use of synthetic pesticides, the insecticidal and repellent activities of neem oil were tested in vitro on fifth instar larvae and adults of S. singularis. Larvae were collected from a cocoa plot. The fifth instar larvae were separated from the other stages. Some of the larvae were reared in the laboratory until adult emergence. The concentrations of neem oil used were 0.5, 1, 1.5, 2 and 2.5 µl.ml-1. Insecticidal tests were carried out by spraying the solutions directly onto the insects. The repellency test was carried out using the preferential zone method on filter paper. The results showed an increasing mortality rate with increasing concentrations of neem oil for both fifth instar larvae and adults. The calculated LC50’s for larvae and adults were 0.89 and 0.98 µl.ml-1 respectively. Neem oil had a weak repellent effect on both fifth instar larvae and adults, with average repellency rates of 23.60% and 28.8% respectively. These results show that neem oil can be an alternative to the use of synthetic pesticides in the control of S. singularis.

Chromosome-level genome assembly of Murraya paniculata sheds light on biosynthesis of floral volatiles

BackgroundMurraya paniculata (L.) Jack, commonly called orange jessamine in the family Rutaceae, is an important ornamental plant in tropical and subtropical regions which is famous for its strong fragrance. Although genome assemblies have been reported for many Rutaceae species, mainly in the genus Citrus, full genomic information has not been reported for M. paniculata, which is a prerequisite for in-depth genetic studies on Murraya and manipulation using genetic engineering techniques. Here, we report a high-quality chromosome-level genome assembly of M. paniculata and aim to provide insights on the molecular mechanisms of flower volatile biosynthesis.ResultsThe genome assembly with a contig N50 of 18.25 Mb consists of 9 pseudomolecules and has a total length of 216.86 Mb. Phylogenetic analysis revealed that M. paniculata diverged from the common ancestor approximately 25 million years ago and has not undergone any species-specific whole genome duplication events. Genome structural annotation and comparative genomics analysis revealed that there are obvious differences in transposon contents among the genomes of M. paniculata and Citrus species, especially in the upstream regions of genes. Research on the flower volatiles of M. paniculata and C. maxima at three flowering stages revealed significant differences in volatile composition with the flowers of C. maxima lacking benzaldehyde and phenylacetaldehyde. Notably, there are transposons inserted in the upstream region of the phenylacetaldehyde synthase (PAAS) genes Cg1g029630 and Cg1g029640 in C. maxima, but not in the upstream region of three PAAS genes Me2G_2379, Me2G_2381, and Me2G_2382 in M. paniculata. Our results indicated that compared to the low expression levels of PAAS genes in C. maxima, the higher expression levels of the three PAAS genes in M. paniculata are the main factor affecting the phenylacetaldehyde biosynthesis and causing the content difference of phenylacetaldehyde. The phenylacetaldehyde synthetic activities of the enzymes encoded by M. paniculata PAAS genes were validated by in vitro analyses.ConclusionsOur study provides useful genomic resources of M. paniculata for further research on Rutaceae plants, identifies new PAAS genes, and provides insights into how transposons contribute to variations in flower volatiles among Murraya and Citrus plants.

Recent Advances in Synthetic Drugs and Natural Actives Interacting with OAT3.

Organic anion transporter 3 (OAT3) is predominantly expressed in the kidney and plays a vital role in drug clearance. Consequently, co-ingestion of two OAT3 substrates may alter the pharmacokinetics of the substrate. This review summarizes drug-drug interactions (DDIs) and herbal-drug interactions (HDIs) mediated by OAT3, and inhibitors of OAT3 in natural active compounds in the past decade. This provides a valuable reference for the combined use of substrate drugs/herbs for OAT3 in clinical practice in the future and for the screening of OAT3 inhibitors to avoid harmful interactions.

Dissecting the roles of peptidoglycan synthetic and autolytic activities in the walled to L-form bacterial transition.

Bacterial cells are surrounded by a peptidoglycan (PG) wall, which is a crucial target for antibiotics. It is well known that treatment with cell wall-active antibiotics occasionally converts bacteria to a non-walled "L-form" state that requires the loss of cell wall integrity. L-forms may have an important role in antibiotic resistance and recurrent infection. Recent work has revealed that inhibition of de novo PG precursor synthesis efficiently induces the L-form conversion in a wide range of bacteria, but the molecular mechanisms remain poorly understood. Growth of walled bacteria requires the orderly expansion of the PG layer, which involves the concerted action not just of synthases but also degradative enzymes called autolysins. Most rod-shaped bacteria have two complementary systems for PG insertion, the Rod and aPBP systems. Bacillus subtilis has two major autolysins, called LytE and CwlO, which are thought to have partially redundant functions. We have dissected the functions of autolysins, relative to the Rod and aPBP systems, during the switch to L-form state. Our results suggest that when de novo PG precursor synthesis is inhibited, residual PG synthesis occurs specifically via the aPBP pathway, and that this is required for continued autolytic activity by LytE/CwlO, resulting in cell bulging and efficient L-form emergence. The failure of L-form generation in cells lacking aPBPs was rescued by enhancing the Rod system and in this case, emergence specifically required LytE but was not associated with cell bulging. Our results suggest that two distinct pathways of L-form emergence exist depending on whether PG synthesis is being supported by the aPBP or RodA PG synthases. This work provides new insights into mechanisms of L-form generation, and specialisation in the roles of essential autolysins in relation to the recently recognised dual PG synthetic systems of bacteria.

Thymus mast cells as a component of neuro-endocrine-immune interactions under stress

Mast cells (MCs) are a required component of the thymus microenvironment. They affect intercellular interactions and permeability of the hematothymic barrier through cytokine production. There is speculation that the thymus is the site of MCs formation and deposition. MCs are under complex neuro-endocrine control and they can play an important role in the process of acute transformation of the thymus in the formation of a stress reaction, affecting the extrathymic migration of cells. The purpose of this study is to assess the functional involvement of MCs in the process of the thymus acute transformation at various hyper- and hypodynamic effects during the formation of stress response and without it.The study was conducted on male Wistar rats. The stress factors were physical activity (swimming) of different intensities and immobilization, which represent two opposite states of dynamic stress. MCs were classified on histological preparations; a degranulation coefficient and a mean histochemical coefficient (synthetic activity) were calculated.In groups with preserved adrenal glands after exposure a significant decrease in the thymus mass coefficient is noted, which indicates a weakening of its functional activity in response to the development of stress. At the same time, MCs of the thymus quickly respond to neuro-endocrine factors under stress. These cells are involved in a general reaction: their activity consists in a synchronous decrease of the synthesis of granules in the cytoplasm and an increased release of active substances accumulated earlier. The mass and structure of the thymus remain unchanged in groups with removed adrenal glands after immobilization. No changes in morphofunctional indicators of mast cells were detected either. Experiments with hypo- and hyperdinamic loading of animals with preserved and removed adrenal glands indicate that the MCs response is largely determined by the hypothalamic-pituitary-adrenal axis of the endocrine system. Removal of the adrenal glands (inability to release glucocorticoids) leads to a lack of functional response from the thymus MCs. The stimulating effect of adrenal glucocorticoids on MCs under stress is carried out in combination with other neuro-endocrine factors (catecholamines, corticotropin-releasing hormone, adrenocorticotropic hormone). When this axis is activated and a full-fledged stress reaction is formed by the body, MCs are actively involved in the process of acute transformation of the thymus through cytokine secretion. These is an important condition for the development of adaptation mechanisms by the immune system.

Visualization of Cellular Membranes in 2D and 3D Conditions Using a New Fluorescent Dithienothiophene S,S-Dioxide Derivative.

Cellular membranes play a key role in cell communication with the extracellular environment and neighboring cells. Any changes, including their composition, packing, physicochemical properties and formation of membrane protrusions may affect cells feature. Despite its great importance, tracking membrane changes in living cells is still a challenge. For investigation of processes related to tissue regeneration and cancer metastasis, such as the induction of epithelial-mesenchymal transition, increased cell motility, and blebbing, the possibility to conduct prolonged observation of membrane changes is beneficial, albeit difficult. A particular challenge is conducting this type of research under detachment conditions. In the current manuscript, a new dithienothiophene S,S-dioxide (DTTDO) derivative is presented as an effective dye for staining the membranes of living cells. The synthetic procedures, physicochemical properties, and biological activity of the new compound are presented herein. In addition to the labeling of the membranes in a monolayer culture, its usefulness for visualization of membranes under detachment conditions is also demonstrated. Obtained data have proven that a new DTTDO derivative may be used to stain membranes in various types of experimental procedures, from traditional 2D cell cultures to unanchored conditions. Moreover, due to the specific optical properties, the background signal is reduced and, thus, observation may be performed without washing.

DNA methylation levels of TaP5CS and TaBADH are associated with enhanced tolerance to PEG-induced drought stress triggered by drought priming in wheat

Drought priming is a promising strategy to enhance tolerance to recurred drought in wheat. However, the underlying mechanisms of priming-induced tolerance are far from clear. Here, three different priming intensities (P1D, P2D, P3D) and two varieties with different sensitivities to drought priming were used to investigate the effects and mechanisms of drought priming. Results showed light (P1D) or moderate (P2D) drought priming intensity induced positive effects for the drought sensitive variety (YM16), while high (P3D) priming intensity brought a negative impact on the plant drought resistant. For drought insensitive one (XM33), light priming intensity had no significant effect on tolerance to drought, while moderate or high intensity showed better priming effects. Moderate priming induced higher leaf water potential and also the osmolytes levels. Consistent with the proline and betaine, the related synthetic enzymatic activities, as well as the expression of TaP5CS and TaBADH were higher in P2D in YM16 and P3D in XM33. The contents of proline and betaine showed a positive correlation with activities of SOD, CAT, GR, AsA, and GSH contents, and a negative correlation with O2.-, H2O2, and MDA contents. Further analysis revealed CG demethylation of ATG-proximal regions in the promoter of TaP5CS and TaBADH were involved in promoting the synthesis of proline and betaine in primed plants. Collectively, these findings demonstrate drought priming effect was variety independent but depended on the priming severity, and demethylation of TaP5CS and TaBADH involved in the accumulation of osmolytes which contribute to the enhanced drought tolerance induced by priming.

PERK-Mediated Cholesterol Excretion from IDH Mutant Glioma Determines Anti-Tumoral Polarization of Microglia.

Isocitrate dehydrogenase (IDH) mutation, a known pathologic classifier, initiates metabolic reprogramming in glioma cells and has been linked to the reaction status of glioma-associated microglia/macrophages (GAMs). However, it remains unclear how IDH genotypes contribute to GAM phenotypes. Here, it is demonstrated that gliomas expressing mutant IDH determine M1-like polarization of GAMs, while archetypal IDH induces M2-like polarization. Intriguingly, IDH-mutant gliomas secrete excess cholesterol, resulting in cholesterol-rich, pro-inflammatory GAMs without altering their cholesterol biosynthesis, and simultaneously exhibiting low levels of tumoral cholesterol due to expression remodeling of cholesterol transport molecules, particularly upregulation of ABCA1 and downregulation of LDLR. Mechanistically, a miR-19a/LDLR axis-mediated novel post-transcriptional regulation of cholesterol uptake is identified, modulated by IDH mutation, and influencing tumor cell proliferation and invasion. IDH mutation-induced PERK activation enhances cholesterol export from glioma cells via the miR-19a/LDLR axis and ABCA1/APOE upregulation. Further, a synthetic PERK activator, CCT020312 is introduced, which markedly stimulates cholesterol efflux from IDH wild-type glioma cells, induces M1-like polarization of GAMs, and consequently suppresses glioma cell invasion. The findings reveal an essential role of the PERK/miR-19a/LDLR signaling pathway in orchestrating gliomal cholesterol transport and the subsequent phenotypes of GAMs, thereby highlighting a novel potential target pathway for glioma therapy.

Engineered GO-Silk Fibroin-Based Hydrogel for the Promotion of Collagen Synthesis in Full-Thickness Skin Defect

In order to improve the regeneration of full-layer skin defects, hydrogels were developed based on the combination of chitosan (Cs), Daba silk fibroin (DSF), and graphene oxide (GO): CS, DSF/Cs and DSF/Cs/GO. The biocompatibility of hydrogels with human dermis fibroblasts in vitro was evaluated using the MTS assay. To assess the regenerative potential of hydrogels, a model of a full-layer skin defect was reconstructed on the back of rats and closed the wound surface with CS, DSF/Cs and DSF/Cs/GO hydrogels. The morphological and morphometric characteristics of regenerate tissues were obtained by staining with hematoxylin-eosin, Heidengain azocarmine, and immunohistochemistry on days 7 and 14 of the experiment. It has been shown that the use of DSF/Cs and DSF/Cs/GO promotes enhanced healing and epithelization of a full-layer skin wound. The addition of GO to the hydrogel increased the synthetic activity of fibroblasts and improved the characteristics of the produced collagen fibers.

Dermal Fibroblasts as the Main Target for Skin Anti-Age Correction Using a Combination of Regenerative Medicine Methods

This article includes the data from current studies regarding the pathophysiological mechanisms of skin aging and the regenerative processes occurring in the epidermis and dermis at the molecular and cellular level, mainly, the key role of dermal fibroblasts in skin regeneration. Analyzing these data, the authors proposed the concept of skin anti-age therapy that is based on the correction of age-related skin changes by stimulating regenerative processes at the molecular and cellular level. The main target of the skin anti-age therapy is dermal fibroblasts (DFs). A variant of the cosmetological anti-age program using the combination of laser and cellular methods of regenerative medicine is presented in the paper. The program includes three stages of implementation and defines the tasks and methods of each stage. Thus, laser technologies allow one to remodel the collagen matrix and create favorable conditions for DFs functions, whereas the cultivated autologous dermal fibroblasts replenish the pool of mature DFs decreasing with age and are responsible for the synthesis of components of the dermal extracellular matrix. Finally, the use of autological platelet-rich plasma (PRP) enables to maintenance of the achieved results by stimulating DF function. It has been shown that growth factors/cytokines contained in α-granules of platelets injected into the skin bind to the corresponding transmembrane receptors on the surface of DFs and stimulate their synthetic activity. Thus, the consecutive, step-by-step application of the described methods of regenerative medicine amplifies the effect on the molecular and cellular aging processes and thereby allows one to optimize and prolong the clinical results of skin rejuvenation.

Role of mechanosensitive Piezo1 receptor expressed on macrophage in Periodontitis

Abstract Objectives: The mechanosensitive Ca 2+ion channels, Piezo1, converts the mechanical stimulus into cell signals in a variety of immune cells. However, the pathophysiological property of Piezo1 in the oral polymicrobial infectious disease of periodontitis is largely unknown. This study investigated the role of Piezo1 in the inflammatory and phagocytic reactions by RAW264.7 macrophages in response to the exposures to periodontal pathogen, P.gingivalis. Experimental methods: Short hairpin RNA (shRNA) vector for Piezo1 or control scrambled sequence was transfected to RAW264.7 cells. Then, RAW264.7 cells were incubated for 24 hours in the presence or absence of whole P.gingivalis(MOI; 10) or outer membrane vesicles (OMVs, 1 μg/ml) isolated from P.gingivalis, w or w/o Yoda1 (synthetic Piezo1 activator), or shear stress. qPCR was used to monitor the mRNA expressions of Piezo1, TNF-α, TLR-2, and TLR-4, whereas TNF-α protein was detected by ELISA. RAW264.7’s phagocytic ability was evaluated by cytoplasm-internalization of pHrodo-labeled whole P.gingivalisor OMVs using a flow cytometer. Results: OMVs induced more TNF-α production and phagocytosis by RAW264.7 cells than whole P.gingivalis, both of which were further upregulated by Yoda1 as well as shear stress (p<0.05, ANOVA). Shear stress combined with OMV-stimulation upregulated the gene expression of TLR-4, while downregulating TLR-2 gene in RAW264.7 cells. The shRNA-targeting Piezo1 significantly suppressed the TNF-α production and internalization of OMVs by RAW264.7 cells compared control scramble shRNA (p<0.05, ANOVA). Conclusion: The present study indicated that mechanical stress may dysregulate the macrophage-mediated innate immune responses in periodontitis. NIH NIDCR grants, DE-027851, DE-028715 and DE-029709

THE CORRELATION OF REACTIVE CHANGES IN THE CORTICAL AND CEREBRAL SUBSTANCE OF THE ADRENAL GLANDS OF WHITE RATS DURING THE CORRECTION OF TESTOSTERONE BLOCKADE AT THE 6TH MONTH OF THE EXPERIMENT

The main pharmacological effect of prolonged injection of a synthetic analogue of gonadotropin-releasing hormone is the development of chemical castration. To correct the reactive changes that develop during testosterone blockade in the organs under study, scientists use the active ingredient quercetin to study its effect on oxidative stress. Its antioxidant effect can be used for pathogenetic therapy and prevention of changes in the body caused by a decrease in testosterone levels [12, 13, 18]. The aim of the study was to investigate morphological changes in corticosterocytes zones of the cortex and medullary endocrinocytes of the adrenal glands of white rats during the correction of central testosterone deprivation at the sixth month of the experiment. Materials and methods: The adrenal glands of 25 male white rats were studied and divided into 3 groups: group 1 – 5 intact rats, group 2 – 10 rats injected with triptorelin acetate subcutaneously at a dose of 0.3 mg of active substance per kg of body weight, and group 3 – 10 rats injected with quercetin 100 mg per kg of body weight once a day 3 times a week for 6 months against the background of triptorelin acetate administration. The average size and volume of the nucleus (N) of corticosterocytes of all cortical zones (CZ), the average size and volume of the nucleus of the ChC, the density of the cords of the adrenal cortex zones and the density of the cords of the adrenal medulla were measured and calculated. Conclusions: 1. Correction of central testosterone deprivation at the 6th month of the experiment causes a decrease in the synthetic activity of corticosterocytes of the glomerular zone and an increase in the protein synthetic function of fascicular zone cells. 2. A significant decrease in the average size of corticosterocytes of the reticular zone and restoration of cytoplasmic basophilia at 6 months of correction proves the positive effect of quercetin on the synthetic activity of these cells. 3. Reduction of the average size and volume of chromophilic endocrinocyte nuclei and increase in their number during the correction of chemical castration at 6 months of the experiment confirms the significant positive effect of quercetin. 4. The revealed correlation between changes in the cells of the glomerular, fascicular and reticular zones of the adrenal cortex and the adrenal medulla of white rats against the background of chemical castration and its correction indicates the involvement of not only hypothalamic-pituitary dependent endocrine organs, but also organs of the sympathoadrenal system.