The effect of the experimental chronic hyperglycemia on the kidney and myocardium

  • Olha Yarmolenko Sumy State University
  • Valentyna Bumeister Sumy State University
  • Stefan Polak Comenius University
  • Olena Gordienko Sumy State University
  • Olha Prykhodko Sumy State University
  • Nadiia Demikhova Sumy State University http://orcid.org/0000-0003-4139-1645
  • Yurii Shkatula Sumy State University
  • Andrii Demikhov Sumy State University
Keywords: hyperglycemia, alloxan, kidney, myocardium, remodeling.

Abstract

Abstract. The number of patients with diabetes increases annually. Modern forecasts predict that diabetes will be the seventh leading cause of death in 2030. Despite many significant advances in the research of diabetes and the use of new modern treatments, the disease is still progressing, and it is necessary to continue to study the effects of diabetes on human systems and organs: kidney and myocardium.

Methods. A total of 24 rats of reproductive age (6 months old) were involved in this experimental study. Experimental rats were injected with alloxan intraperitoneally once at a dose of 20 mg/100 g on an empty stomach. In addition, they received a 10% glucose solution 24 hours after alloxan injection and a 5% glucose solution during the experiment. We measured glucose level with Accu-Chek Advantage (Boehringer, Germany) after 2, 12, and 24 hours after alloxan injection, and then weekly. The subjects of the investigation were kidney and heart of the experimental (n=12) and control (n=12) animals for correct comparative analysis.

Results. The average blood glucose level remained at 11 mmol/L ± 2 mmol/L. During the experimental period, the rats' weight gain, dilation of both ventricles and relative renal weight gain were determined. By the histological examination of the myocardium, we revealed polymorphic nuclei, perinuclear cytolysis, fragmentation, wavy-like deformation of cardiomyocytes, stromal and perivascular edema, uneven filling of blood vessels, and local fibrosis. Thinning of fibrous capsule and cortical layer, destruction of nephrons, and hemorrhages were detected in the kidney.

Conclusions. Our study confirms the robustness of alloxan-induced hyperglycemia in rats. We came to this conclusion because the early changes in the kidneys and heart are explained by the development of microangiopathies, which is a typical feature of the pathogenesis of diabetes. With prolonged exposure to chronic hyperglycemia, structural disorders of vital organs are worsened. This experimental model could be used for conducting comprehensive research aimed to study the mechanisms of diabetes mellitus, the effects of hyperglycemia on organs and tissues, and correct the complications.

Downloads

Download data is not yet available.

References

International Diabetes Federation. IDF Diabetes Atlas, 9th edn. Brussels, Belgium: 2019. Available at: https://www.diabetesatlas.org.

Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med. 2006;3(11):e442. doi: 10.1371/journal.pmed.0030442.

Maslova OV, Suncov JuI. Epidemiology of diabetes mellitus and microvascular complications. Diabetes mellitus. 2011;3:6-11.

Pankiv V.I. Diabetes mellitus: definition, classification, epidemiology, risk factors. International Endocrynological  Journal. 2013;7(55):95-104.

de Leeuw TG, Mangiarini L, Lundin R, Kaguelidou F, van der Zanden T, Pasqua OD, rt al; GAPP consortium. Gabapentin as add-on to morphine for severe neuropathic or mixed pain in children from age 3 months to 18 years - evaluation of the safety, pharmacokinetics, and efficacy of a new gabapentin liquid formulation: study protocol for a randomized controlled trial. Trials. 2019;20(1):49. doi: 10.1186/s13063-018-3169-3. Erratum in: Trials. 2019;20(1):368.

Demikhova N, Cherkashyna L, Chernatska O et al. The relationship between lipid metabolism and albuminuration level with single nucleotide polymorphism -204a>c [rs 3808607] CYP7A1 gene in patients with 2 type diabetes mellitus and diabetic nephropathy. Romanian Journal of Diabetes, Nutrition and Metabolic Diseases. 2019;26(3):253-261. doi: 10.2478/rjdnmd-2019-0026.

Chernatska O, Demikhova N, Rudenko T et al. Assessment of the lipid profile correction in patients with arterial hypertension and type 2 diabetes mellitus. Azerbaijan Medical Journal. 2019;1:95-99.

Chernatska O, Demikhova N. Improvement of treatment in persons with arterial hypertension and type 2 diabetes mellitus. Georgian Medical News. 2018;11(284):47-51.

Marushchak M, Krynytska I, Mikolenko A, Andreychyn Yu, Bodnar Ya, Chornomydz I. Chronic heart failure causes osteopathy or is osteopathy a factor in development of chronic heart failure? Asian Journal of Pharmaceutical and Clinical Research. 2018;11(1):111-115. doi: 10.22159/ajpcr.2018.v11i1.17532.

 Popov SV, Melekhovets OK, Demikhova NV, Vynnychenko LB, Khil'ko IeS, Tychyna DO, Murga IV. Application of "reytoil" in prevention of atherosclerosis in diabetes patients. Lik Sprava. 2012 ;(8):119-26. [In Ukrainian].

Siddiqui A, Siddiqui S, Ahmad S et al. Diabetes: Mechanism, Pathophysiology and Management. A Review International Journal of Drug Development & Research. 2013;5(2):1-23.

Tkachenko VI, Vydyborets NV, Kovalenko OF. Analysis of the prevalence and incidence of diabetes mellitus and its complications among the population of Ukraine and in the Kyiv region for 2004-2013. Achievements of clinical and experimental medicine. 2014;2:177-182. doi:10.22141/2224-0721.14.3.2018.136426.

Woynarowska-Sołdan M, Yezhova O, Sytnyk O, Węziak-Białowolska D. Positive health behaviours Polish and Ukrainian medical students in the context of chronic diseases. Przegl Epidemiol. 2018;72(4):509-523. doi: 10.32394/pe.72.4.26.

Tamayo T, Rosenbauer J, Wild SH, Spijkerman AM, Baan C, Forouhi NG, et al. Diabetes in Europe: an update. Diabetes Res Clin Pract. 2014 Feb;103(2):206-17. doi: 10.1016/j.diabres.2013.11.007.

Sattar N. Revisiting the links between glycaemia, diabetes and cardiovascular disease. Diabetologia. 2013 Apr;56(4):686-95. doi: 10.1007/s00125-012-2817-5.

de Ferranti SD, de Boer IH, Fonseca V, Fox CS, Golden SH, Lavie CJ, et al. Type 1 diabetes mellitus and cardiovascular disease: a scientific statement from the American Heart Association and American Diabetes Association. Circulation. 2014 Sep 23;130(13):1110-30. doi: 10.1161/CIR.0000000000000034.

Chawla A, Chawla R, Jaggi S. Microvasular and macrovascular complications in diabetes mellitus: Distinct or continuum?. Indian J Endocrinol Metab. 2016;20(4):546-551. doi:10.4103/2230-8210.183480.

Chougale AD, Panaskar SN, Gurao PM et al. Optimization of Alloxan Dose is Essential to Induce Stable Diabetes for Prolonged Period. Asian Journal of Biochemistry. 2007;2(6):402-408. doi:10.3923/AJB.2007.402.408.

Ighodaro OM, Adeosun AM, Akinloye OA. Alloxan-induced diabetes, a common model for evaluating the glycemic-control potential of therapeutic compounds and plants extracts in experimental studies. Medicina (Kaunas). 2017;53(6):365-374. doi: 10.1016/j.medici.2018.02.001.

Jain DK, Arya RK. Anomalies in alloxan-induced diabetic model: It is better to standardize it first. Indian J Pharmacol. 2011;43(1):91. doi:10.4103/0253-7613.75684.

Mostafavinia A, Amini A, Ghorishi SK, Pouriran R, Bayat M. The effects of dosage and the routes of administrations of streptozotocin and alloxan on induction rate of type1 diabetes mellitus and mortality rate in rats. Lab Anim Res. 2016;32(3):160-165. doi: 10.5625/lar.2016.32.3.160.

 Lenzen S. The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia. 2008 Feb;51(2):216-26. doi: 10.1007/s00125-007-0886-7.

Korol LV, Mygal LYa, Stepanova NM. Intensity of oxidative stress and activity of angiotensin converting enzyme in blood of patients with uncomplicated pyelonephritis. Ukr.Biochem.J. 2017;89(2):99-105. doi: 10.15407/ubj89.02.099.

Demikhova N, Yarmolenko O, Teslyk T, Bumeister V, Prykhodko O, Dmytruk S. The remodeling of lung under the influence of alloxan-induced hypergycemia. Romanian Journal of Diabetes Nutrition and Metabolic Diseases. 2020;27(1):45-49. doi :10.46389/rjd-2020-1008.

Shkatula YV, Badion YO, Tkachenko YA et al. Epidemiology of injuries in children resulting from a fall from a height. Azerbaijan Medical Journal. 2021;2.

Misra M, Aiman U. Alloxan: an unpredictable drug for diabetes induction?. Indian J Pharmacol. 2012;44(4):538-539. doi:10.4103/0253-7613.99348.

Cherkashyna L, Konoval N, Shklyar A, Kyrychenko I, Haidash O, Demikhova N. Study of structural and biochemical changes in the muscular tissue of the oesophagus for solving the problem of diagnosing the prescription of death coming. Pol Merkur Lekarski. 2020;48(283):42-44.

Cherkashyna L, Konoval N, Shklyar A, Najar S, Haidash O, Kuts L, Gortinskaya O, Demikhova N. The dynamics of changes in biochemical markers of the state of tissue in intercostal muscles during the early postmortem period. Pol Merkur Lekarski. 2020;48(283):45-48.

Cherkashyna L, Shklyar A, Demikhova N, Protsenko O, Kicha N, Sukhonosov R, Singh HH, Sytiuk T. Lipofuscin content in the muscle tissue during the early postmortem period: improvement of forensic diagnosis of the prescription of death coming. Pol Merkur Lekarski. 2020;48(284):93-96.

Cherkashyna L, Shklyar A, Sukhonosov R, Miroshnikova O, Naguta L, Olkhovskiy V. Cholinesterase in different types of the muscle tissue during the early postmortem period for diagnosis of death coming.  Bangladesh Journal of Medical Science. 2021;20(1):95-100.  doi:10.3329/bjms.v20i3.50352  

Etuk EU. Animals models for studying diabetes mellitus. Agriculture and Biology Journal of North America. 2010;1(2):130-134.

Grytsiuk MI, Bojchyk TM, Petryshen OI. Comparative characteristics of experimental models of diabetes mellitus. World of Medicine and Biology. 2014;2(44):199-203.

Guzyk MM, Dyakun KO, Yanytska LV, Pryvrotska IB, Krynytska IYa, Pishel IM. Inhibitors of Poly(ADP-Ribose) Polymerase-1 as Agents Providing Correction of Brain Dysfunctions Induced by Experimental Diabetes. Neurophysiology. 2017;49(3):183-193. 10.1007/s11062-017-9672-4.  

Krynytska I, Marushchak M. The Indices of Nitric Oxide System in Rats with Carrageenan-Induced Enterocolitis Combined with Diabetes Mellitus. Romanian Journal of Diabetes, Nutrition and Metabolic Diseases. 2018;25(3):283-288. doi: 10.2478/rjdnmd-2018-0033.

Shkatula YV, Badion YO, Novikov MV. Efficiency of different methods of temporary external hemostasis at the pre-hospital stage of emergency medical care. Novosti Khirurgii. 2021;28(6):688–693. doi: 10.18484/2305-0047.2020.6.688.

Prykhodko O, Gulaya V, Yarmolenko O et al. Microscopic changes in the organs of rats under conditions of general dehydration of the organism. Azerbaijan Medical Journal. 2016;4:95-100.

Sakata N, Yoshimatsu G, Tsuchiya H, Egawa S, Unno M. Animal models of diabetes mellitus for islet transplantation. Exp Diabetes Res. 2012;2012:256707. doi: 10.1155/2012/256707.

Yarmolenko O, Sikora V, Bumeister V, Prykhodko O, Demikhova N, Bumeister L. Age-dependent cardioprotective action of meldonium on heart remodeling under the experimental hypoosmolar hyperhydration. Bangladesh J Med Sci. 2019;18(2):395-401.  doi:10.3329/bjms.v18i2.40714.

Zaragoza C, Gomez-Guerrero C, Martin-Ventura JL, Blanco-Colio L, Lavin B, Mallavia B, Tarin C, Mas S, Ortiz A, Egido J. Animal models of cardiovascular diseases. J Biomed Biotechnol. 2011;2011:497841. doi: 10.1155/2011/497841.

Avtandilov GG. Moscow, Meditsina Publ., 2002, 240 pp.

Degen AS, Krynytska IY, Kamyshnyi AM. Changes in the transcriptional activity of the entero-insular axis genes in streptozotocin-induced diabetes and after the administration of TNF-α non-selective blockers. Endocr Regul. 2020;54(3):160-171. doi: 10.2478/enr-2020-0019.

Jain M. Histopathological changes in diabetic kidney disease. Clinical Queries: Nephrology. 2012;1(2):127-133.

Pourghasem M, Shafi H, Babazadeh Z. Histological changes of kidney in diabetic nephropathy. Caspian J Intern Med. 2015;6(3):120-7.

Yamamoto T, Nakamura T, Noble NA, Ruoslahti E, Border WA. Expression of transforming growth factor beta is elevated in human and experimental diabetic nephropathy. Proc Natl Acad Sci U S A. 1993;90(5):1814-1818. doi:10.1073/pnas.90.5.1814.

Mora-Fernández C, Domínguez-Pimentel V, de Fuentes MM, Górriz JL, Martínez-Castelao A, Navarro-González JF. Diabetic kidney disease: from physiology to therapeutics. J Physiol. 2014;592(18):3997-4012. doi: 10.1113/jphysiol.2014.272328.

Czekalski S. Diabetic nephropathy and cardiovascular diseases. Roczniki Akademii Medycznej w Białymstoku. 2005;50:122-125.

Toth-Manikowski S, Atta MG. Diabetic Kidney Disease: Pathophysiology and Therapeutic Targets. J Diabetes Res. 2015;2015:697010. doi:10.1155/2015/697010.

Vasylchenko VS, Korol LV, Kuchmenko OB, Stepanova NM. The oxidative status in patients with chronic kidney disease. Ukrainian Biochemical Journal. 2020;92(5):70–77. doi.org/10.15407/ubj92.05.070.

Vilhova I, Kryvko YY, Maciejewski R. The radioanatomical research of plural renal arteries. Folia Morphol (Warsz). 2001;60(4):337-41.


Abstract views: 820
PDF Downloads: 21216
Published
2021-05-13
How to Cite
Yarmolenko, O., Bumeister, V., Polak, S., Gordienko, O., Prykhodko, O., Demikhova, N., Shkatula, Y., & Demikhov, A. (2021). The effect of the experimental chronic hyperglycemia on the kidney and myocardium. Ukrainian Journal of Nephrology and Dialysis, (3(71), 3-10. https://doi.org/10.31450/ukrjnd.3(71).2021.01