Metabolic and immune accompaniments of electrocardiographic and morphologic gastric mucosa parameters in naїve and stressed rats
DOI:
https://doi.org/10.12775/JEHS.2024.61.54947Keywords
acute water-immersion and restraint stress, damage to the ECG and gastric mucosa, immunity, metabolome, relationships, ratsAbstract
Introduction and aim. Earlier, by applying the water-immersion and restraint stress (WIRS) model, we reproduced primary attributes of stress and found that the severity of the damage to the gastric mucosa correlates with changes in ECG parameters, which indicate myocardial dystrophy. Further, it was found that such a connection is caused by the damaging effect on both targets of increasing the level of parathyroid hormone, as well as the production of aldosterone and catecholamines by enlarged adrenal glands. In addition, an increase in the level of corticosterone and sympathetic tone with a simultaneous decrease in vagal tone as well as serum calcitonin and testosterone cause damage to the gastric mucosa, but not to the myocardium. Such a constellation of neuro-endocrine reactions to stressors determines the severity of damage to the gastric mucosa and myocardium by 73%. The purpose of this study is to find out metabolic and immune accompaniments of electrocardiogram and gastric mucosa parameters in naїve and stressed rats.
Material and methods. The experiment is at 18 male and 20 female Wistar rats. Over the 10 days, one animal remained intact and 3 other rats were exposed to WIRS. The next day after stressing, immune and metabolic parameters as well as ECG and gastric mucosa injuries was recorded.
Results. Serum levels of Phosphates, Сatalase and α-LP Cholesterol as well as erythrocyte level of Potassium and Na,K-ATPase activity of the erythrocyte are positively correlated with ECG markers of myocardial damage, and negatively correlated with visual markers of damage to the gastric mucosa. Erythrocyte level of Sodium and serum levels of Potassium and Alkaline Phosphatase reflect the intactness of the gastric mucosa only. While serum level of Calcium reflects damage to the gastric mucosa. Taken together, the listed metabolic factors determine the morpho-functional state of the gastric mucosa and myocardium by 72% (R=0.851). Damage to the gastric mucosa and myocardium is more severe, the lower the bactericidal activity of blood neutrophils, and the greater the mass of the thymus. The spleen mass and the content of fibroblasts in the thymus are negatively correlated only with the severity of damage to the gastric mucosa, while the percentages of reticulocytes and lymphoblasts in the spleen are positively correlated with it. Finally, the higher the percentage of macrophages in the thymus, the deeper the damage to the myocardium. The canonical correlation between the listed immune parameters and markers of the two targets of stressors is very strong (R=0.809).
Conclusion. Water-immersion and restraint stress causes changes in the neuro-endocrine-immune complex, which lead to changes in the metabolome and damage to the gastric mucosa and myocardium.
References
Andreyeva LI, Kozhemyakin LA, Kishkun AA. Modification of the method for determining the lipid peroxide in the test with thiobarbituric acid [in Russian]. Laboratornoye Delo. 1988;11:41-43.
Baevsky RM, Berseneva AP. Use KARDIVAR system for determination of the stress level and estimation of the body adaptability. Standards of measurements and physiological interpretation. Moscow-Prague;2008:41.
Besedovsky H & Sorkin E. Network of immune-neuroendocrine interaction. Clin Exp Immunol. 1977. 27(1):1-12. PMCID: PMC1540898
Besedovsky H & del Rey A. Immune-neuro-endocrine interactions: facts and hypotheses. Endocrine reviews. 1996. 17(1), 64–102. https://doi.org/10.1210/edrv-17-1-64
Bilas VR, Popovych IL. Role of microflora and organic substances of water Naftussya in its modulating influence on neuroendocrine-immune complex and metabolism [in Ukrainian]. Medical Hydrology and Rehabilitation. 2009;7(1):68-102.
Bilas VR, Popadynets’ OO, Flyunt ISS, et al. Entropies of thymocytogram, splenocytogram, immunocytogram and leukocytogram in rats are regulated by sex and the neuroendocrine parameters while regulates immune parameters. JEHS. 2020;10(7):266-288.
Berger EN. Neurohumoral Mechanisms of Disturbed Tissue Trophism [in Russian]. Kyїv: Zdorovya;1980:104.
Clementi G, Caruso A, Fiore CE, et al. Effect of parathyroid hormone, centrally or peripherally injected, on gastric activity in male rats. Eur J Pharmacol. 1989;166(3):549-552. doi: 10.1016/0014-2999(89)90374-9.
Castle C, Tietjens J. Perforated gastric ulcer as the initial manifestation of hyperparathyroidism. BMJ Case Rep. 2021;14(4):e240570. doi: 10.1136/bcr-2020-240570.
Clementi G, Prato A, Rapisarda E, et al. Inhibition of restraint stress by systemic (Asu1,7) eel-calcitonin. J Endocrinol Invest. 1985;8(6):543-546. doi: 10.1007/BF03348558.
Dhabhar FS, McEwen BS. Acute stress enhances while chronic stress suppresses immune function in vivo: a potential role for leukocyte trafficking. Brain Behav Immun. 1997;11:286–306.
Dhabhar FS. Enhancing versus suppressive effects of stress on immune function: implications for immunoprotection and immunopathology. NeuroImmunoModulation. 2009;16:300–317.
Dhabhar FS. The short-term stress response – mother nature’s mechanism for enhancing protection and performance under conditions of threat, challenge, and opportunity. Front Neuroendocrinol. 2018;49:175–192.
Dubinina YY, Yefimova LF, Sofronova LN, Geronimus AL. Comparative analysis of the activity of superoxide dismutase and catalase of erythrocytes and whole blood from newborn children with chronic hypoxia [in Russian]. Laboratornoye Delo. 1988;8:16-19.
Elsenbruch S, Enck P. The stress concept in gastroenterology: from Selye to today. F1000Res. 2017;6:2149. doi: 10.12688/f1000research.12435.1.
Evangelista S. Role of calcitonin gene-related Peptide in gastric mucosal defence and healing. Curr Pharm Des. 2009;15(30):3571-3576. doi: 10.2174/138161209789207024.
Evangelista S, Renzi D. A protective role for calcitonin gene-related peptide in water-immersion stress-induced gastric ulcers in rats. Pharmacol Res. 1997;35(4):347-350. doi: 10.1006/phrs.1997.0142.
Fihura OA, Melnyk OI, Ruzhylo SV, et al. Relationships between neuro-endocrine, electrocardiogram, and gastric mucosal damage parameters in naїve and stressed rats. Journal of Education, Health and Sport. 2023; 18(1): 162-190.
Gavrilov VB, Mishkorudnaya MI. Spectrophotometric determination of plasma levels of lipid hydroperoxides [in Russian]. Laboratornoye Delo. 1983;3:33-36.
Goryachkovskiy AM. Clinical biochemistry [in Russian]. Odesa: Astroprint,1998:608.
Gozhenko AI, Korda MM, Popadynets OO, Popovych IL. Entropy, Harmony, Synchronization and Their Neuro-Endocrine-Immune Correlates [in Ukrainian]. Odesa: Feniks;2021:232.
Gozhenko АІ, Korda MM, Smagliy SS, et al. Uric Acid, Metabolism, Neuro-Endocrine-Immune Complex [in Ukrainian]. Odesa: Feniks;2023:266. doi.org/10.5281/zenodo.7575158
Guidobono F, Netti C, Pagani F, et al. Effect of unmodified eel calcitonin on gastric acid secretion and gastric ulcers in the rat. Farmaco. 1991;46(4):555-563.
Harrington EC. The Desirability Function. Industrial Quality Control. 1965;21:494-498.
Hiller G. Test for the quantitative determination of HDL cholesterol in EDTA plasma with Reflotron®. Klin Chem. 1987;33:895-898.
Horizontov PD, Belousova BI, Fedotova MI. Stress and the Blood System [in Russian]. Мoskva: Меditsina;1983:240.
Hotta H, Onda A, Suzuki H, Milliken P, Sridhar A. Modulation of Calcitonin, Parathyroid Hormone, and Thyroid Hormone Secretion by Electrical Stimulation of Sympathetic and Parasympathetic Nerves in Anesthetized Rats. Front Neurosci. 2017;11:375. doi: 10.3389/fnins.2017.00375.
Keshavarzi Z, Mohebbati R, Mohammadzadeh N, Alikhani V. The protective role of estradiol & progesterone in male rats, following gastric ischemia-reperfusion. Acta Endocrinol (Buchar). 2018;14(1):30-35. doi: 10.4183/aeb.2018.30.
Konturek PC, Brzozowski T, Konturek SJ, et al. Influence of bacterial lipopolysaccharide on healing of chronic experimental ulcer in rat. Scand J Gastroenterol. 2001 Dec;36(12):1239-47. doi: 10.1080/003655201317097065. PMID: 11761011.
Korneva EA. Pathways of neuro-immune communication: past and present time, clinical application [in Russian]. Meditsinskaya Immunologiya. 2020;22(3):405-418. doi:10.15789/1563-0625-PON-1974.
Korolyuk MA, Ivanova MI, Mayorova IG, Tokarev VYe. The method for determining the activity of catalase [in Russian]. Laboratornoye Delo. 1988;1:16-19.
Kozyavkina NV, Popovych IL, Popovych DV, et al. Sexual dimorphism in some psycho-neuro-endocrine parameters at human. JEHS. 2021;11(5):370-391.
Kozyavkina OV. The state of post-stress parameters of autonomic homeostasis and endocrine, metabolic and immune status and the relationship between them in rats with alternative types of pre-stress autonomic homeostasis induced by bioactive water Naftussya [in Ukrainian]. Medical Hydrology and Rehabilitation. 2009;7(2):40-56.
Kozyavkina OV, Kozyavkina NV, Gozhenko OA, et al. Bioactive Water Naftussya and Neuro-Endocrine-Immune Complex [in Ukrainian]. Kyїv: UNESCO-SOCIO;2015:349.
Kulchynskyi AB, Gozhenko AI, Zukow W, Popovych IL. Neuro-immune relationships at patients with chronic pyelonephrite and cholecystite. Communication 3. Correlations between parameters EEG, HRV and Immunogram. Journal of Education, Health and Sport. 2017;7(3):53-71.
Kuehl P, Baczako K, Stanescu A, Malfertheimer P. Loss of alkaline phosphatase activity in duodenal mucosa: a marker for precursorsof gastric metaplasia? J Pathol. 1990. 162(4):317-322.
Kwiecien S, Magierowska K, Magierowski M, et al. Role of sensory afferent nerves, lipid peroxidation and antioxidative enzymes in the carbon monoxide-induced gastroprotection against stress ulcerogenesis. J Physiol Pharmacol. 2016 Oct;67(5):717-729. PMID: 28011952.
Lu S, Wu D, Sun G, et al. Gastroprotective effects of Kangfuxin against water-immersion and restraint stress-induced gastric ulcer in rats: roles of antioxidation, anti-inflammation, and pro-survival. Pharmaceutical biology. 2019;57(1):770–777. doi.org/10.1080/ 13880209. 2019.1682620
Luo XJ, Liu B, Dai Z, et al. Stimulation of calcitonin gene-related peptide release through targeting capsaicin receptor: a potential strategy for gastric mucosal protection. Dig Dis Sci. 2013;58(2):320-325. doi: 10.1007/s10620-012-2362-6.
Machowska A, Szlachcic A, Pawlik M, et al. The role of female and male sex hormones in the healing process of preexisting lingual and gastric ulcerations. J Physiol Pharmacol. 2004;55(Suppl 2):91-104. PMID: 15608364.
Machowska A, Brzozowski T, Sliwowski Z, et al. Gastric secretion, proinflammatory cytokines and epidermal growth factor (EGF) in the delayed healing of lingual and gastric ulcerations by testosterone. Inflammopharmacology. 2008;16(1):40-47. doi: 10.1007/s10787-007-1600-6.
Makarenko YeV. ATPase activity of erythrocytes in patients with chronic liver and stomach disease [in Russian]. Laboratornoye Delo. 1987;2:14-17.
Markova OO, Popovych IL, Tserkovnyuk AV, Barylyak LG. Adrenaline Myocardiodystrophy and Reactivity of the Organism [in Ukrainian]. Kyїv: Computerpress;1997:126.
Meerson FZ. Adaptation, Stress and Prophylaxis [in Russian]. Moskva:Nauka;1981:279.
Meerson FZ. Pathogenesis and prevention of stress and ischemic heart damage [in Russian]. Moskva: Meditsina;1984:272.
Melnyk OI, Chendey IV, Zukow W, et al. The features of reactions to acute stress of neuro-endocrine-immune complex, metabolome, ECG and gastric mucosa in rats with various state of innate muscular endurance and resistance to hypoxia. JEHS. 2023;38(1):96-128.
Melnyk OI, Struk ZD, Zukow W, Popovych IL. Vegetative, endocrine and metabolic accompaniments of individual immune responses to adaptogenic balneotherapy. Journal of Education, Health and Sport. 2019;9(12):207-229.
Melnyk OI, Zukow W, Hrytsak MV, et al. Canonical analysis of neuroendocrine-metabolic and neuroendocrine-immune relationships at female rats. JEHS. 2021;11(5):356-369.
Mizunashi K, Furukawa Y, Katano K, et al. Effect of omeprazole, an inhibitor of H+,K+-ATPase, on bone resorption in humans. Calcif Tissue Int. 1993; 53(61): 21-25.
Moghadam ZM, Henneke P, Kolter J. From flies to men: ROS and the NADPH oxidase in phagocytes. Front Cell Dev Biol. 2021; 9:628991. doi: 10.3389/fcell.2021.628991
Nakamura J, Takada S, Ohtsuka N, et al. An assessment of gastric ulcers in vivo: enhancement of urinary recovery after oral administration of phenolsulfonphthalein in rats. J Pharmacobiodynamics. 1984;7(7):485-491. doi.org/10.1248/bpb1978.7.485
Nance DM, Sanders VM. Autonomic innervation and regulation of immune system (1987-2007). Brain Behav Immun. 2007;21(6):736-745.
Oh ES, Steele CN, You Z, et al. Sex hormones and the risk of cardiovascular disease and mortality in male and female patients with chronic kidney disease: A systematic review and meta-analysis. Physiol Rep. 2022;10(22):e15490. doi: 10.14814/phy2.15490.
Ohno H, Noguchi M, Takayanagi N. Effect of elcatonin on experimental gastric and duodenal ulcers. Jpn J Pharmacol. 1985;37(1):67-75. doi: 10.1254/jjp.37.67.
Panossian AG, Efferth T, Shikov AN, et al. Evolution of the adaptogenic concept from traditional use to medical systems: Pharmacology of stress‐ and aging‐related diseases. Med Res Rev. 2021;41:630–703. 10.1002/med.21743
Panossian A, Efferth T. Network Pharmacology of Adaptogens in the Assessment of Their Pleiotropic Therapeutic Activity. Pharmaceuticals (Basel). 2022;15(9):1051. doi: 10.3390/ph15091051.
Pavlov VA, Chavan SS, Tracey KJ. Molecular and functional neuroscience in immunity. Annu Rev Immunol. 2018;36:783-812.
Perederiy VG, Zemskov AM, Bychkova NG, Zemskov VM. Immune Status, Principles of its Evaluation and Correction of Immune Disorders [in Russian]. Kyїv: Zdorovya;1995:211.
Polovynko IS, Zayats LM, Zukow W, Popovych IL. Neuro-endocrine-immune relationships by chronic stress at male rats. Journal of Health Sciences. 2013; 3(12): 365-374.
Polovynko IS, Zajats LM, Popovych AI, Popovych IL. Іntegral quantification of neuroendocrine and immune responses to chronic stress in male rats [in Ukrainian]. In: Pathophysiology and Pharmacy: ways of integration: Abstracts VII National Congress pathophysiologists Ukraine with international participation (5-7 October 2016). Kharkiv: NPhU;2016:182-182.
Popadynets O, Gozhenko A, Badyuk N, et al. Interpersonal differences caused by adaptogen changes in entropies of EEG, HRV, immunocytogram, and leukocytogram. Journal of Physical Education and Sport. 2020; 20(Suppl. 2): 982-999.
Popovych IL. Factor and canonical analyzes of the parameters of the neuro-endocrine-immune complex, metabolism and erosive-ulcerative lesions of the gastric mucosa in rats under acute water-immersion stress [in Ukrainian]. Medical Hydrology and Rehabilitation. 2007;5(2):68-80.
Popovych IL, Kulchynskyi AB, Korolyshyn TA, Zukow W. Interrelations between changes in parameters of HRV, EEG and cellular immunity at patients with chronic pyelonephritis and cholecystitis. JEHS. 2017;7(10):11-23.
Popovych IL, Kulchynskyi AB, Gozhenko AI, et al. Interrelations between changes in parameters of HRV, EEG and phagocytosis at patients with chronic pyelonephritis and cholecystitis. JEHS. 2018;8(2):135-156.
Popovych IL, Gozhenko AI, Zukow W, Polovynko IS. Variety of Immune Responses to Chronic Stress and their Neuro-Endocrine Accompaniment. Riga:Scholars' Press;2020: 172. doi.org/10.5281/zenodo.3822074
Popovych IL, Gozhenko AI, Korda MM, Klishch IM, Popovych DV, Zukow W (editors). Mineral Wa-ters, Metabolism, Neuro-Endocrine-Immune Complex. Odesa. Feniks;2022:252. doi.org/10.5281/zenodo.6604298
Popovych IL, Bombushkar IS, Żukow X, Kovalchuk HY. Uric acid, neuroendocrine-immune complex and metabolism: relationships. JEHS. 2023;36(1):135-159.
Selye H: A syndrome produced by diverse nocuous agents. 1936. J Neuropsychiatry Clin Neurosci. 1998;10(2):230–231. 10.1176/jnp.10.2.230a
Shannon CE. A mathematical theory of information. Bell Syst Tech J. 1948;27:379-423.
Stiel D, Murray DJ, Peters TJ. Mucosal enzyme activities, with special reference to enzymes implicated in bicarbonate secretion, in the duodenum of rats with cysteamine-induced ulcers. Clin Sci (Lond). 1983; 64(63):341-347.
Szabo S, Yoshida M, Filakovszky J, Juhasz G. "Stress" is 80 Years Old: From Hans Selye Original Paper in 1936 to Recent Advances in GI Ulceration. Curr Pharm Des. 2017;23(27):4029-4041. doi: 10.2174/1381612823666170622110046.
Taché Y, Saperas E. Potent inhibition of gastric acid secretion and ulcer formation by centrally and peripherally administered interleukin-1. Ann N Y Acad Sci. 1992;664:353-68. doi: 10.1111/j.1749-6632.1992.tb39774.x. PMID: 1456663.
Thayer JF, Sternberg EM. Neural aspects of immunomodulation: Focus on the vagus nerve. Brain Behav Immun. 2010;24(8):1223-1228.
Tracey KJ. Understanding immunity requires more than immunology. Nature Immunology. 2010;11(7):561-564.
Uehara A, Okumura T, Kitamori S, et al. Gastric antisecretory and antiulcer actions of interleukin-1. Evidence for the presence of an "immune-brain-gut" axis. J Clin Gastroenterol. 1992;14 Suppl 1:S149-55. PMID: 1629572.
Uribe-Querol E & Rosales C. Phagocytosis: Our Current Understanding of a Universal Biological Process. Frontiers in immunology. 2020;11:1066. https://doi.org/10.3389/fimmu.2020.01066
Vasilenko VKh & Kochina EN (editors). Neurohumoral Regulation of Digestion [in Russian]. Moskva: Meditsina;1983:368.
Vetvik K, Schrumpf E, Andersen KJ. et al. Effect of misoprostol and antacids on gastric and duodenal mucosal enzyme activities in duodenal ulcer patients. Scand J Gastroenterol. 1991;26(64):385-391.
Vetvik K, Schrumpf E, Mowinckel P, et al. Effects of omeprazole and eradication of Helicobacter pylory on gastric and duodenal mucosal enzyme activities and DNA in duodenal ulcer patients. Scand J Gastroenterol. 1994;29(611): 995-1000.
Wang M, Gu H, Brewster BD, Huang C. Role of endogenous testosterone in TNF-induced myocardial injury in males. Int J Clin Exp Med. 2012;5(2):96-104. PMID: 22567171; PMCID: PMC3342716.
Ward TL, Watkins KL, Southern LL, et al. Interactive effects of sodium zeolite-A and copper in growing swine: growth, and bone and tissue mineral concentrations. J Anim Sci. 1991;69(62):726-733.
Zajats LM, Polovynko IS, Zukow W, et al. Neuroendocrine-immune relatioships in rat females. JEHS. 2017;7(10):59-78.
Zavodskaya IS & Moreva YeV. Pharmacological Analysis of Mechanism of Stress and its Effects [in Russian]. Moskva: Meditsina;1981:216.
Zhao DQ, Xue H, Sun HJ. Nervous mechanisms of restraint water-immersion stress-induced gastric mucosal lesion. World J Gastroenterology. 2020;26(20):2533–2549. doi.org/10.3748/wjg.v26.i20.2533
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Oksana Fihura, Mykhaylo Korda, Ivan Klishch, Sofiya Ruzhylo, Oksana Melnyk, Walery Zukow, Roman Yanchij, Alyona Vorobienko, Oleksandr Plyska, Igor Popovych
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The periodical offers access to content in the Open Access system under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0
Stats
Number of views and downloads: 48
Number of citations: 0