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  • 1
    In: Journal of Applied Physiology, American Physiological Society, Vol. 130, No. 3 ( 2021-03-01), p. 759-771
    Abstract: Traumatic stress causes posttraumatic stress disorder (PTSD). PTSD is associated with cardiovascular diseases and risk of sudden cardiac death in some subjects. We compared effects of predator stress (PS, cat urine scent, 10 days) on mechanisms of cardiac injury and protection in experimental PTSD-vulnerable (PTSD) and -resistant (PTSDr) rats. Fourteen days post-stress, rats were evaluated with an elevated plus-maze test, and assigned to PTSD and PTSDr groups according to an anxiety index calculated from the test results. Cardiac injury was evaluated by: 1) exercise tolerance; 2) ECG; 3) myocardial histomorphology; 4) oxidative stress; 5) pro- and anti-inflammatory cytokines. Myocardial heat shock protein 70 (HSP70) was also measured. Experimental PTSD developed in 40% of rats exposed to PS. Exercise tolerance of PTSD rats was 25% less than control rats and 21% less than PTSDr rats. ECG QRS, QT, and OTc intervals were significantly longer in PTSD rats than in control and PTSDr rats. Only cardiomyocytes of PTSD rats had histomorphological signs of metabolic and hypoxic injury and impaired contractility. Oxidative stress markers were higher in PTSD than in PTSDr rats. Pro-inflammatory IL-6 was higher in PTSD rats than in control and PTSDr rats, and anti-inflammatory IL-4 was lower in PTSD than in control and PTSDr rats. Myocardial HSP70 was lower in PTSD rats than in PTSDr and control rats. Our conclusion was that rats with PTSD developed multiple signs of cardiac injury. PTSDr rats were resistant also to cardiac injury. Factors that limit cardiac damage in PS rats include reduced inflammation and oxidative stress and increased protective HSP70. NEW & NOTEWORTHY For the first time, rats exposed to stress were segregated into experimental PTSD (ePTSD)-susceptible and ePTSD-resistant rats. Cardiac injury, ECG changes, and impaired exercise tolerance were more pronounced in ePTSD-susceptible rats. Resistance to ePTSD was associated with decreased inflammation and oxidative stress and with increased protective heat shock protein 70. Results may help identify individuals at high risk of PTSD and also provide a foundation for developing preventive and therapeutic means to restrict PTSD-associated cardiac morbidity.
    Type of Medium: Online Resource
    ISSN: 8750-7587 , 1522-1601
    RVK:
    RVK:
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2021
    detail.hit.zdb_id: 1404365-8
    SSG: 12
    SSG: 31
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  • 2
    In: Morphological newsletter, Reaviz Medical University, Vol. 30, No. 4 ( 2022-12-14), p. 60-66
    Abstract: Dermal fibroblast cell culture is a convenient model for studying various effects on cells, including hypoxia. Fibroblasts, in addition to collagen production, are able to synthesize biogenic amines, hormones, neuropeptides, and neurotransmitters identical to those in the central nervous and endocrine systems, which allows them to be used to study cellular disorders in various diseases. The purpose of the study was to evaluate the functional changes in the culture of dermal fibroblasts under hypoxic conditions using biochemical and molecular biological methods. In cells of fibroblast culture under normoxia (air and 5% CO 2 in an incubator) and hypoxic exposure (a mixture of gases - 95% N 2 and 5% CO 2 ) at 1 and 3 hours, biochemical methods were used to determine the activity of aspartate aminotransferase (AsAT), alanine aminotransferase (AlAT), gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH), glucose levels, concentrations of ATP, ADP, AMP, as well as the level of mRNA expression of the hypoxia-induced factor Hif-1a and the nuclear factor Nf-κb by polymerase chain reaction. It was shown that under hypoxic exposure at 1 hour in fibroblast culture, cell viability, glucose levels and activity of LDH, AlAT, AsAT decrease, the amount of ATP decreases, after 3 hours there is a tendency to normalize all indicators. Adaptive mechanisms make it possible to normalize the functioning of cells under hypoxic conditions from 1 to 3 hours. The results obtained in the evaluation of metabolic changes at different times of hypoxic exposure (1 and 3 hours) in the culture of rat fibroblasts indicate a high adaptive capacity of connective tissue cells - fibroblasts at a lack of oxygen. The study of intracellular parameters during hypoxia, the determination of critical points depending on the time of exposure will determine the directions for further study of the mechanisms of cell adaptation, which, perhaps, will complement the tactics of compensatory effects in ischemia of tissues of various genesis. The revealed changes reflect the adaptive response of the fibroblast culture in response to hypoxic exposure.
    Type of Medium: Online Resource
    ISSN: 2686-8741 , 1812-3171
    URL: Issue
    Language: Unknown
    Publisher: Reaviz Medical University
    Publication Date: 2022
    detail.hit.zdb_id: 2831428-1
    SSG: 12
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  • 3
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2020-09-28)
    Abstract: It is a common fact, that the content of sex hormones in humans and animals varies in different age periods. The functional state of the immune system also changes with age. However, sex differences studies of inflammatory and immune responses during puberty prevail in literature. Investigation of immune responses to LPS peculiarities in prepubertal females and males may contribute to the development of more effective immunotherapy and minimize side effects of children vaccination. Therefore, the aim of this work was to investigate the LPS-induced SIRS sex differences in prepubertal Wistar rats. Despite the absence of sex differences in estradiol and testosterone levels, LPS-induced inflammatory changes in liver and lungs are more pronounced among males. Males demonstrate the increasing neopterin, corticosterone levels and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity. Not less important is that in females, demonstrating less morphological changes in liver and lungs, endotoxin level is tenfold higher, and corticosterone level decreases. Thus, endotoxin cannot be used as a marker of the severity of multiple organ failure in prepubertal period. The LPS-induced immune reactions in females and males are similar and are characterized by immunosuppression. Both females and males have decreased production of cytokines (IL-2, IL-4, TNF-α, TGF-β) and the absolute number of CD3 + and CD3 + CD8 + lymphocytes in blood. The acute atrophy of thymus and apoptosis of thymic cells are revealed in animals of both sexes. However, the number of CD3 + CD4 + T-helpers and CD4 + CD25 + Foxp3 + T-cells decreases only in females with SIRS, and in males there was a decrease of CD45R + B-cells. The least expressed sex differences in immune responses in the prepubertal period can be determined by the low levels of sex steroids and the absence of their immunomodulatory effect. Further studies require the identification of mechanisms, determining the sex differences in the inflammatory and immune responses in prepubertal animals.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2615211-3
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  • 4
    In: International Journal of Inflammation, Hindawi Limited, Vol. 2019 ( 2019-04-01), p. 1-17
    Abstract: On the model of the systemic inflammatory response (SIRS), induced by lipopolysaccharide (LPS), the morphological and functional changes in the thymus and spleen and the subpopulation composition of peripheral blood lymphocytes of rats differing in resistance to hypoxia were studied. It was demonstrated that the level of endotoxin in blood serum after 3 hours of LPS administration in susceptible-to-hypoxia rats was 64 times higher than in the control group, while in tolerant-to-hypoxia animals it was only 8 times higher in 6 hours. After 24 hours of LPS injection, only in susceptible-to-hypoxia rats did the level of C-reactive protein in blood serum increase. There is a difference in the dynamics of morphological changes of lymphoid organs after LPS injection in tolerant- and susceptible-to-hypoxia animals. After 3 hours of LPS administration, the tolerant-to-hypoxia rats showed no changes in the thymus, spleen, and subpopulation composition of lymphocytes in peripheral blood. After 6 hours there was only a decrease in B-lymphocytes and increase in cytotoxic T-lymphocytes and NK cells. After 1 day of LPS injection, the tolerant-to-hypoxia rats had devastation in PALS of the spleen. After 3 hours of LPS injection the susceptible-to-hypoxia animals had reactive changes in the lymphoid organs: decrease of the thymus cortex, narrowing of the marginal zones of spleen lymphoid follicles, widening of their germinal centers, and a decrease in the absolute number of cytotoxic T-lymphocytes, NK cells, and B-lymphocytes. After 24 hours of LPS injection the tolerant-to-hypoxia animals had a greater absolute number of T-lymphocytes and NK cells in comparison with the susceptible rats. Thus, in animals with different resistance to hypoxia the LPS-induced SIRS is characterized by different dynamics of morphological and functional changes of the thymus and spleen. The obtained data will serve as a basis for the development of new individual approaches to the prevention and treatment of infectious and inflammatory diseases.
    Type of Medium: Online Resource
    ISSN: 2090-8040 , 2042-0099
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2019
    detail.hit.zdb_id: 2573900-1
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  • 5
    In: BMC Complementary Medicine and Therapies, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2021-12)
    Abstract: The dysfunction of the thyroid gland is a common medical condition. Nowadays, patients frequently use medicinal herbs as complementary or alternative options to conventional drug treatments. These patients may benefit from treatment of thyroid dysfunctions with Potentilla alba L. preparations. While it has been reported that Potentilla alba preparations have low toxicity, nothing is known about their ability to affect reproductive functions in patients of childbearing age. Methods Male Wistar rats were orally treated with a thyrotrophic botanical drug, standardized Potentilla alba Dry Extract (PADE), at doses 8 and 40 times higher than the median therapeutic dose recommended for the clinical trials, for 60 consecutive days. Male Wistar rats receiving water (H 2 O) were used as controls. After completing treatment, half of the PADE-treated and control males were used to determine PADE gonadotoxicity, and the remaining half of PADE-treated and control males were mated with intact females. Two female rats were housed with one male for two estrus cycles. PADE effects on fertility and fetal/offspring development were evaluated. Results Herein, we report that oral treatment of male Wistar rats with PADE before mating with intact females instigated marked effects on male reproductive organs. Treatment significantly decreased the motility of the sperm and increased the number of pathological forms of spermatozoa. Additionally, a dose-dependent effect on Leydig cells was observed. However, these PADE effects did not significantly affect male fertility nor fetal and offspring development when PADE-treated males were mated with intact females. Conclusions PADE treatment of male rates negatively affected sperm and testicular Leydig cell morphology. However, these changes did not affect male fertility and offspring development. It is currently not known whether PADE treatment may affect human male fertility and offspring development. Therefore, these results from an animal study need to be confirmed in humans. Results from this animal study can be used to model the exposure-response relationship and adverse outcomes in humans.
    Type of Medium: Online Resource
    ISSN: 2662-7671
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 3037610-5
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  • 6
    In: Journal of Inflammation Research, Informa UK Limited, Vol. Volume 12 ( 2019-03), p. 73-86
    Type of Medium: Online Resource
    ISSN: 1178-7031
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2019
    detail.hit.zdb_id: 2494878-0
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