Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Research Article

The Treatment of Prednisone in Mild Diabetic Rats: Biochemical Parameters and Cell Response

Author(s): Mariana P.R. Machado, Aline Z. Schavinski, Amanda L. Deluque, Gustavo T. Volpato and Kleber E. Campos*

Volume 20, Issue 5, 2020

Page: [797 - 805] Pages: 9

DOI: 10.2174/1871530319666191204130007

Price: $65

Abstract

Background: Limited studies have been carried out with prednisone (PRED) in treatment by glucose intolerant individuals, even in this model the animals presented low blood glucose levels at adulthood, by the high regenerative capacity of β-cell.

Objective: The aim was to evaluate the effects of the treatment of PRED in mild diabetes on biochemical and immunological biomarkers.

Methods: Rats were randomly divided into four groups: control (C), treated control C+PRED (treatment of 1.25 mg/Kg/day PRED); diabetic DM (mild diabetes) and treated diabetic DM+PRED (treatment with same dose as C+PRED group). Untreated groups received vehicle, adjusted volume to body weight. The treatment lasted 21 days and measured body weight, food and water intake, and glycemia weekly. In the 3rd week, the Oral Glucose Tolerance Test (OGTT) and the Insulin Tolerance Test (ITT) was performed. On the last day, the rats were killed and the blood was collected for biochemical analyzes, leukogram and immunoglobulin G levels.

Results: There was a significant decrease in body weight in mild diabetes; however, the treatment in diabetic groups increased food intake, glycemia, and the number of total leukocytes, lymphocytes and neutrophils. On the other hand, it decreased the levels of triglycerides, high-density and very lowdensity lipoproteins. In addition, diabetic groups showed glucose intolerance and mild insulin resistance, confirming that this model induces glucose intolerant in adult life.

Conclusion: The results showed that the use of prednisone is not recommended for glucose intolerant individuals and should be replaced in order to not to aggravate this condition.

Keywords: Diabetes, glucocorticoids, glycometabolism, immunosuppressant, lipometabolism, prednisone.

« Previous
Graphical Abstract
[1]
Hanson, M.A.; Gluckman, P.D. Developmental origins of health and disease--global public health implications. Best Pract. Res. Clin. Obstet. Gynaecol., 2015, 29(1), 24-31.
[http://dx.doi.org/10.1016/j.bpobgyn.2014.06.007] [PMID: 25225058]
[2]
Hyder, A.A.; Wosu, A.C.; Gibson, D.G.; Labrique, A.B.; Ali, J.; Pariyo, G.W. Noncommunicable disease risk factors and mobile phones: a proposed research agenda. J. Med. Internet Res., 2017, 19(5)e133
[http://dx.doi.org/10.2196/jmir.7246] [PMID: 28476722]
[3]
Puchulu, F.M. Definition, Diagnosis and Classification of Diabetes Mellitus.Dermatology and Diabetes; Springer: Cham, 2018, pp. 7-18.
[http://dx.doi.org/10.1007/978-3-319-72475-1_2]
[4]
Boles, A.; Kandimalla, R.; Reddy, P.H. Dynamics of diabetes and obesity: Epidemiological perspective. Biochim. Biophys. Acta Mol. Basis Dis., 2017, 1863(5), 1026-1036.
[http://dx.doi.org/10.1016/j.bbadis.2017.01.016] [PMID: 28130199]
[5]
Atlas, I.D. 2015.
[6]
López-Soldado, I.; Herrera, E. Different diabetogenic response to moderate doses of streptozotocin in pregnant rats, and its long-term consequences in the offspring. Exp. Diabesity Res., 2003, 4(2), 107-118.
[http://dx.doi.org/10.1155/EDR.2003.107] [PMID: 14630572]
[7]
Damasceno, D.C.; Sinzato, Y.K.; Bueno, A.; Netto, A.O.; Dallaqua, B.; Gallego, F.Q.; Piculo, F. Mild diabetes models and their maternal-fetal repercussions. Journal of Diabetes Research. 2013, Article ID 473575, 1-9.
[8]
Iessi, I.L.; Sinzato, Y.K.; Gallego, F.Q.; Nielsen, J.H.; Damasceno, D.C. Effect of diabetes on circulating pancreatic hormones in pregnant rats and their offspring. Horm. Metab. Res., 2016, 48(10), 682-686.
[http://dx.doi.org/10.1055/s-0042-114039] [PMID: 27632150]
[9]
Gallego, F.Q.; Miranda, C.A.; Sinzato, Y.K.; Iessi, I.L.; Dallaqua, B.; Volpato, G.T.; Damasceno, D.C. Distribution of pancreatic islet endocrine cells and antioxidant enzymes in streptozotocin-injected rats during postnatal critical development window. Life Sci., 2019.
[10]
Triplitt, C. Drug interactions of medications commonly used in diabetes. Diabetes Spectr., 2006, 19(4), 202-211.
[http://dx.doi.org/10.2337/diaspect.19.4.202]
[11]
Hu, C.; Jia, W. Diabetes in China: epidemiology and genetic risk factors and their clinical utility in personalized medication. Diabetes, 2018, 67(1), 3-11.
[http://dx.doi.org/10.2337/dbi17-0013] [PMID: 29263166]
[12]
Heffler, E.; Madeira, L.N.G.; Ferrando, M.; Puggioni, F.; Racca, F.; Malvezzi, L.; Passalacqua, G.; Canonica, G.W. Inhaled Corticosteroids Safety and Adverse Effects in Patients with Asthma. J. Allergy Clin. Immunol. Pract., 2018, 6(3), 776-781.
[http://dx.doi.org/10.1016/j.jaip.2018.01.025] [PMID: 29408385]
[13]
Arafah, B.M. Pharmacology of Glucocorticoids.Adrenal Disorders; Humana Press: Cham, 2018, pp. 67-81.
[http://dx.doi.org/10.1007/978-3-319-62470-9_3]
[14]
Bavaresco, L.; Bernardi, A.; Battastini, A.M.O. Glicocorticóides: Usos clássicos e emprego no tratamento do câncer. Infarma, 2005, 17(7), 9.
[15]
Santos, T.M.M.; Sinzato, Y.K.; Gallego, F.Q.; Iessi, I.L.; Volpato, G.T.; Dallaqua, B.; Damasceno, D.C. Extracellular HSP70 levels in diabetic environment in rats. Cell Stress Chaperones, 2015, 20(4), 595-603.
[http://dx.doi.org/10.1007/s12192-015-0581-4] [PMID: 25813004]
[16]
Pinheiro, M.S.; Rodrigues, L.S.; S, L.; Moraes-Souza, R.Q.; Soares, T.S.; Américo, M.F.; Campos, K.E.; Damasceno, D.C.; Volpato, G.T. Effect of Bauhinia holophylla treatment in Streptozotocin-induced diabetic rats. An. Acad. Bras. Cienc., 2017, 89(1), 263-272.
[http://dx.doi.org/10.1590/0001-3765201720160050] [PMID: 28225851]
[17]
Justina, V.D.; dos Passos, R.R. Junior; Bressan, A. F.; Tostes, R. C.; Carneiro, F. S.; Soares, T. S. Life Sci., 2018, 205, 18-25.
[http://dx.doi.org/10.1016/j.lfs.2018.05.013] [PMID: 29746846]
[18]
Anti, S.M.A.; Giorgi, R.D.N.; Chahade, W.H. Antiinflamatórios hormonais: glicocorticóides. Einstein (Sao Paulo), 2008, 6(1), 159-165.
[19]
Oliveira-Braga, K.A.; Nepomuceno, N.A.; Correia, A.T.; Jatene, F.B.; Pêgo-Fernandes, P.M. Effects of prednisone on mucociliary clearance in a murine model. Transplant. Proc., , 2012, 44(8), 2486-2489. [Elsevier.].
[http://dx.doi.org/10.1016/j.transproceed.2012.07.053] [PMID: 23026626]
[20]
Gelding, S.V.; Robinson, S.; Lowe, S.; Niththyananthan, R.; Johnston, D.G. Validation of the low dose short insulin tolerance test for evaluation of insulin sensitivity. Clin. Endocrinol. (Oxf.), 1994, 40(5), 611-615.
[http://dx.doi.org/10.1111/j.1365-2265.1994.tb03012.x] [PMID: 8013142]
[21]
Tai, M.M. A mathematical model for the determination of total area under glucose tolerance and other metabolic curves. Diabetes Care, 1994, 17(2), 152-154.
[http://dx.doi.org/10.2337/diacare.17.2.152] [PMID: 8137688]
[22]
Young, D.S.; Friedman, R.B. Effects of disease on clinical laboratory tests; Amer Assn for Clinical Chemistry, 2001, Vol. 1, .
[23]
Knopfholz, J.; Disserol, C.C.D.; Pierin, A.J.; Schirr, F.L.; Streisky, L.; Takito, L.L.; Massucheto Ledesma, P.; Faria-Neto, J.R.; Olandoski, M.; da Cunha, C.L.; Bandeira, A.M. Validation of the friedewald formula in patients with metabolic syndrome. Cholesterol, 2014, 2014261878
[http://dx.doi.org/10.1155/2014/261878] [PMID: 24672715]
[24]
Xavier, H.T.; Izar, M.C.; Faria Neto, J.R.; Assad, M.H.; Rocha, V.Z.; Sposito, A.C.; Fonseca, F.A.; dos Santos, J.E.; Santos, R.D.; Bertolami, M.C.; Faludi, A.A.; Martinez, T.L.; Diament, J.; Guimarães, A.; Forti, N.A.; Moriguchi, E.; Chagas, A.C.; Coelho, O.R.; Ramires, J.A. [V Brazilian Guidelines on Dyslipidemias and Prevention of Atherosclerosis]. Arq. Bras. Cardiol., 2013, 101(4)(Suppl. 1), 1-20.
[http://dx.doi.org/10.5935/abc.2013S010] [PMID: 24217493]
[25]
Garber, A.J.; Abrahamson, M.J.; Barzilay, J.I.; Blonde, L.; Bloomgarden, Z.T.; Bush, M.A.; Dagogo-Jack, S.; DeFronzo, R.A.; Einhorn, D.; Fonseca, V.A.; Garber, J.R.; Garvey, W.T.; Grunberger, G.; Handelsman, Y.; Hirsch, I.B.; Jellinger, P.S.; McGill, J.B.; Mechanick, J.I.; Rosenblit, P.D.; Umpierrez, G.E. Consensus statement by the American association of clinical endocrinologists and American college of endocrinology on the comprehensive type 2 diabetes management algorithm - 2018 executive summary. Endocr. Pract., 2018, 24(1), 91-120.
[http://dx.doi.org/10.4158/CS-2017-0153] [PMID: 29368965]
[26]
Ochoa-Amaya, J.E.; Marino, L.P.; Tobaruela, C.N.; Namazu, L.B.; Calefi, A.S.; Margatho, R.; Gonçalves, V., Jr; Queiroz-Hazarbassanov, N.; Klein, M.O.; Palermo-Neto, J.; de Oliveira, A.P.L.; de O Massoco, C.; Felicio, L.F. Attenuated allergic inflammatory response in the lungs during lactation. Life Sci., 2016, 151, 281-287.
[http://dx.doi.org/10.1016/j.lfs.2016.03.027] [PMID: 26979776]
[27]
Olson, B.J.; Markwell, J. Assays for determination of protein concentration.Curr. Protoc. Protein Sci.,, 2007. Chapter 3(1), 4.
[PMID: 18429326]
[28]
Whicher, J.T.; Warren, C.; Chambers, R.E. Immunochemical assays for immunoglobulins. Ann. Clin. Biochem., 1984, 21(Pt 2), 78-91.
[http://dx.doi.org/10.1177/000456328402100202] [PMID: 6424545]
[29]
Martínez, B.B.; Pereira, A.C.C.; Muzetti, J.H.; Telles, F.P.; Mundim, F.G.L.; Teixeira, M.A. Experimental model of glucocorticoid-induced insulin resistance. Acta Cir. Bras., 2016, 31(10), 645-649.
[http://dx.doi.org/10.1590/S0102-865020160100000001] [PMID: 27828596]
[30]
Lin, S.; Huang, J.; Zheng, L.; Liu, Y.; Liu, G.; Li, N.; Wang, K.; Zou, L.; Wu, T.; Qin, L.; Cui, L.; Li, G. Glucocorticoid-induced osteoporosis in growing rats. Calcif. Tissue Int., 2014, 95(4), 362-373.
[http://dx.doi.org/10.1007/s00223-014-9899-7] [PMID: 25086673]
[31]
Schwartz, M.W.; Seeley, R.J.; Zeltser, L.M.; Drewnowski, A.; Ravussin, E.; Redman, L.M.; Leibel, R.L. Obesity pathogenesis: an Endocrine Society scientific statement. Endocr. Rev., 2017, 38(4), 267-296.
[http://dx.doi.org/10.1210/er.2017-00111] [PMID: 28898979]
[32]
Dias, A.S.; Llesuy, S.; Marroni, C.A.; Marroni, N. Alterações gastrointestinais no diabetes mellitus: estresse oxidativo e fluxo sangüíneo da artéria mesentérica--estudo experimental. Arq. Gastroenterol., 2004, 41(2), 108-113.
[http://dx.doi.org/10.1590/S0004-28032004000200008] [PMID: 15543384]
[33]
Luo, L.; Liu, M. Adipose tissue in control of metabolism. J. Endocrinol., 2016, 231(3), R77-R99.
[http://dx.doi.org/10.1530/JOE-16-0211] [PMID: 27935822]
[34]
Angelini, C. The role of corticosteroids in muscular dystrophy: a critical appraisal. Muscle Nerve, 2007, 36(4), 424-435.
[http://dx.doi.org/10.1002/mus.20812] [PMID: 17541998]
[35]
Torres, R.P.A.; Torres, R.F.A.; Torres, R.A.; Torres, R.S.L.A. Pulse therapy combined with oral corticosteroids in the management of severe rheumatic carditis and rebound. Cardiol. Young, 2018, 28(2), 309-314.
[http://dx.doi.org/10.1017/S1047951117002062] [PMID: 29065944]
[36]
Cardinali, D.P. Third Level: The Hypothalamus.Autonomic Nervous System; Springer: Cham, 2018, pp. 175-244.
[http://dx.doi.org/10.1007/978-3-319-57571-1_5]
[37]
Lam, F.Y.&; Fleckman, A.M. Acute hyperglycemic syndromes: diabetic ketoacidosis and the hyperosmolar state.Principles of Diabetes Mellitus; Springer: Boston, MA, 2010, pp. 281-295.
[38]
Layton, A.T.; Vallon, V. SGLT2 inhibition in a kidney with reduced nephron number: modeling and analysis of solute transport and metabolism. Am. J. Physiol. Renal Physiol., 2018, 314(5), F969-F984.
[http://dx.doi.org/10.1152/ajprenal.00551.2017] [PMID: 29361669]
[39]
Dunn, B.R.; Ichikawa, I.; Pfeffer, J.M.; Troy, J.L.; Brenner, B.M. Renal and systemic hemodynamic effects of synthetic atrial natriuretic peptide in the anesthetized rat. Circ. Res., 1986, 59(3), 237-246.
[http://dx.doi.org/10.1161/01.RES.59.3.237] [PMID: 2945668]
[40]
Pandey, K.N. Biology of natriuretic peptides and their receptors. Peptides, 2005, 26(6), 901-932.
[http://dx.doi.org/10.1016/j.peptides.2004.09.024] [PMID: 15911062]
[41]
Freitas, Thais Helena Proença de, & Souza, Daniella Abbruzzini Ferreira de. Corticosteróides sistêmicos na prática dermatológica. Parte I: Principais efeitos adversos. An. Bras. Dermatol., 2007, 82(1), 63-70.
[http://dx.doi.org/10.1590/S0365-05962007000100009]
[42]
Petersen, M.C.; Vatner, D.F.; Shulman, G.I. Regulation of hepatic glucose metabolism in health and disease. Nat. Rev. Endocrinol., 2017, 13(10), 572-587.
[http://dx.doi.org/10.1038/nrendo.2017.80] [PMID: 28731034]
[43]
Joslin, E.P.; Kahn, C.R., Eds.; Joslin’s Diabetes Mellitus; Lippincott Williams & Wilkins, 2005.
[44]
Campos, K.E.D.; Sinzato, Y.K.; Damasceno, D.C.; Rudge, M.V.C. Obesidade e resistência à insulina. Femina, 2006, 34(9), 591-595.
[45]
Pereira, R.M.; Moura, L.P.D.; Muñoz, V.R.; Silva, A.S.R.D.; Gaspar, R.S.; Ropelle, E.R.; Pauli, J.R. Molecular mechanisms of glucose uptake in skeletal muscle at rest and in response to exercise. Motriz,, 2017. 23. [SPE].
[http://dx.doi.org/10.1590/s1980-6574201700si0004]
[46]
Kahn, C.R.; Weir, G.C.; King, G.L.; Jacobson, A.M.; Moses, A.C.; Smith, R.J. Joslin: Diabetes Melito-14; Artmed Editora, 2009.
[47]
Rodríguez, V.; Newman, J.D.; Schwartzbard, A.Z. Towards more specific treatment for diabetic dyslipidemia. Curr. Opin. Lipidol., 2018, 29(4), 307-312.
[http://dx.doi.org/10.1097/MOL.0000000000000528] [PMID: 29878904]
[48]
Viana, M.R.; Rodriguez, T.T. Complicações cardiovasculares e renais no diabetes mellitus. Rev. Ciênc. Méd. Biol., 2011, 10(3), 290-296.
[http://dx.doi.org/10.9771/cmbio.v10i3.5892]
[49]
Lottenberg, A.M.P. Importância da gordura alimentar na prevenção e no controle de distúrbios metabólicos e da doença cardiovascular. Arq. Bras. Endocrinol. Metabol, 2009, 53(5), 595-607.
[http://dx.doi.org/10.1590/S0004-27302009000500012] [PMID: 19768250]
[50]
Parhofer, K.G. The Treatment of Disorders of Lipid Metabolism. Dtsch. Arztebl. Int., 2016, 113(15), 261-268.
[http://dx.doi.org/10.3238/arztebl.2016.0261] [PMID: 27151464]
[51]
Okonkwo, U.; DiPietro, L. Diabetes and wound angiogenesis. International journal of molecular sciences, , 2016, 18(7), 1419.
[http://dx.doi.org/10.3390/ijms18071419]
[52]
Rajendran, P.; Chen, Y.F.; Chen, Y.F.; Chung, L.C.; Tamilselvi, S.; Shen, C.Y.; Day, C.H.; Chen, R.J.; Viswanadha, V.P.; Kuo, W.W.; Huang, C.Y. The multifaceted link between inflammation and human diseases. J. Cell. Physiol., 2018, 233(9), 6458-6471.
[http://dx.doi.org/10.1002/jcp.26479] [PMID: 29323719]
[53]
Roumelioti, M.E.; Ing, T.S.; Rondon-Berrios, H.; Glew, R.H.; Khitan, Z.J.; Sun, Y.; Malhotra, D.; Raj, D.S.; Agaba, E.I.; Murata, G.H.; Shapiro, J.I.; Tzamaloukas, A.H. Principles of quantitative water and electrolyte replacement of losses from osmotic diuresis. Int. Urol. Nephrol., 2018, 50(7), 1263-1270.
[http://dx.doi.org/10.1007/s11255-018-1822-0] [PMID: 29511980]
[54]
Otton, R.; Mendonça, J.R.; Curi, R. Diabetes causes marked changes in lymphocyte metabolism. J. Endocrinol., 2002, 174(1), 55-61.
[http://dx.doi.org/10.1677/joe.0.1740055] [PMID: 12098663]
[55]
Ptaschinski, C.; Lukacs, N.W. Acute and chronic inflammation induces disease pathogenesis. In: Molecular Pathology; Academic Press, 2018; pp. 25-43.
[http://dx.doi.org/10.1016/B978-0-12-802761-5.00002-X]
[56]
Hunter, M.C.; Teijeira, A.; Halin, C. T Cell Trafficking through Lymphatic Vessels. Front. Immunol., 2016, 7, 613.
[http://dx.doi.org/10.3389/fimmu.2016.00613] [PMID: 28066423]
[57]
Chun, T.T.; Potz, B.A.; Young, W.A.; Ayala, A. Overview of the Molecular Pathways and Mediators of Sepsis. In: Sepsis; Humana Press: Cham, 2017; pp. 47-69.
[http://dx.doi.org/10.1007/978-3-319-48470-9_4]
[58]
Saffar, A.S.; Ashdown, H.; Gounni, A.S. The molecular mechanisms of glucocorticoids-mediated neutrophil survival. Curr. Drug Targets, 2011, 12(4), 556-562.
[http://dx.doi.org/10.2174/138945011794751555] [PMID: 21504070]
[59]
Holland, J.F.; Frei, E. Cancer Medicine Six; BC Decker, 2003, Vol. 2, .
[60]
Cain, D.W.; Cidlowski, J.A. Immune regulation by glucocorticoids. Nat. Rev. Immunol., 2017, 17(4), 233-247.
[http://dx.doi.org/10.1038/nri.2017.1] [PMID: 28192415]
[61]
Petrillo, M.G.; Bortner, C.D.; Cidlowski, J.A. Glucocorticoids: inflammation and immunity. In: The Hypothalamic-Pituitary-Adrenal Axis in Health and Disease; Springer: Cham, 2017; pp. 43-63.
[http://dx.doi.org/10.1007/978-3-319-45950-9_3]
[62]
Fernandes, A.M.; Valera, F.C.P.; Anselmo-Lima, W.T. Mechanism of action of glucocorticoids in nasal polyposis. Rev. Bras. Otorrinolaringol. (Engl. Ed.), 2008, 74(2), 279-283.
[http://dx.doi.org/10.1016/S1808-8694(15)31101-0] [PMID: 18568209]
[63]
Dhabhar, F.S.; Miller, A.H.; McEwen, B.S.; Spencer, R.L. Stress-induced changes in blood leukocyte distribution. Role of adrenal steroid hormones. J. Immunol., 1996, 157(4), 1638-1644.
[PMID: 8759750]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy