Is anti-IgE therapy effective in preventing magnesium and selenium loss in bones of mice with chronic allergic asthma?

Year 2023, , 319 - 326, 15.09.2023

Serkan Gürgül , Can Demirel Ozlem Keskin , Fatma Betül Şeker , Mehmet Yaşar Özkars , Nurten Erdal Coşar Uzun , Yahya Nural

https://doi.org/10.5798/dicletip.1360644

Abstract

Objective: Chronic allergic asthma (CA) is a respiratory disease that affects millions of people worldwide. While there is evidence linking airway hyperresponsiveness and asthma to factors related to bone metabolism, the impact of asthma on bone health is not well understood. Therefore, to explore whether: (i) CA causes meaningful changes in bone magnesium (Mg) and selenium (Se) levels, and if any, (ii) anti-IgE (anti-immunoglobulin E) treatment has a protective effect against these changes.
Methods: In present study used tibia bones from a previous study on CA in mice. A murine model was used to generate CA. Thirty-two BALB/c male mice were randomly divided into four equal sized groups (eight mice/group): control group (intact), CA (treated with saline (0.9% NaCl), CA+L-AIgE (100 μg of anti-IgE), CA+H-AIgE (200 μg of anti-IgE). After immunization, saline was administered by inhalation three times a week. Anti-IgE applications were performed intraperitoneally for a total of 8 weeks in five sessions with 15-day intervals. Bone Mg and Se levels are determined by inductively coupled plasma mass spectrometry (ICP-MS), which is used to determine the elemental composition of various samples.
Results: Mg levels of CA and CA+L-AIgE groups were significantly decreased compared to the control (P<0.01 for both comparisons). The mean Mg level of the CA+H-AIgE group was close to the control, and the difference was not significant. In all study groups, Se levels were significantly reduced compared to the control (P<0.05 for the CA group, P<0.01 for CA+L-AIgE and CA+H-AIgE groups). No other significant difference was detected among the groups.
Conclusion: Our study provides solid evidence of an association between CA and lower levels of Mg and Se in bones. Current data also showed that anti-IgE therapy can partially and dose-dependently prevent Mg loss induced by CA. These results have significant implications for the treatment and management of bone problems associated with asthma, highlighting the potential for anti-IgE use as a viable treatment for preventing and treating bone mineral metabolism abnormalities in asthma patients.

Keywords

Asthma, Anti-IgE, ICP-MS, Mineral Loss, Magnesium, Selenium

References

• 1.Alwarith J, Kahleova H, Crosby L, et al. The role ofnutrition in asthma prevention and treatment. NutrRev. 2020;78(11):928-938.https://doi.org/10.1093/nutrit/nuaa005
• 2.Çil B, Kabak M, Topçu AF, Taylan M, Sezgi C. TheProper use of Inhalers in a Third Step Hospital and itsEffect on Treatment: Original Study. Dicle Tıp Dergisi.2019;46(2):321-325. https://doi.org/10.5798/dicletip.574929
• 3.FDA. Highlights of prescribing information forXolair® (omalizumab). U.S. Food and DrugAdministration (FDA), Maryland, USA. Reference ID:3955374. [Internet] [cited 2023 June 22]. Availablefrom:https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/103976s5225lbl.pdf
• 4.European Medicines Agency (EMA). Xolair(omalizumab): Summary of Product Characteristics.[Internet] [cited 2023 June 22]. Available from:https://www.ema.europa.eu/en/documents/product-information/xolair-epar-product-information_en.pdf
• 5.Jung JW, Kang HR, Kim JY, et al. Are asthmaticpatients prone to bone loss? Ann Allergy AsthmaImmunol. 2014;112(5):426-431.https://doi.org/10.1016/j.anai.2014.02.013
• 6.Hussein MT, Yousef LM, Abdelwahed SA. Serumlevels of vitamin D, magnesium, and calcium in patientswith stable bronchial asthma. Egypt J Chest DisTubercul. 2019;68:542-
• 545.https://doi.org/10.4103/ejcdt.ejcdt_204_18
• 7.Gürgül S, Keskin Ö, Demirel C, Yaşar Özkars M, NuralY.Does anti-IgE therapy prevent chronic allergicasthma-related bone deterioration in asthmatic mice?J Biomech. 2022;141:111180.https://doi.org/10.1016/j.jbiomech.2022.111180
• 8.Rondanelli M, Faliva MA, Tartara A, et al. An updateon magnesium and bone health. Biometals.2021;34(4):715-736.https://doi.org/10.1007/s10534-021-00305-0
• 9.Yang T, Lee SY, Park KC, et al. The effects of selenium on bone health: from element to therapeutics.Molecules. 2022;27(2):392.https://doi.org/10.3390/molecules27020392
• 10.Ozkars MY, Keskin O, Tokur M, et al. Comparing theeffects of fluticasone, anti-IgE and anti-TNF treatmentsin a chronic asthma model. Allergol Immunopathol(Madr). 2018;46(3):226-234.https://doi.org/10.1016/j.aller.2017.07.003
• 11.Temelkovski J, Hogan SP, Shepherd DP, Foster PS,Kumar RK. An improved murine model of asthma:selective airway inflammation, epithelial lesions andincreased methacholine responsiveness followingchronic exposure to aerosolised allergen. Thorax. 1998;53(10):849-856. https://doi.org/10.1136/thx.53.10.849
• 12.Sagara H, Masuda H, Ota M, et al. Neutralizing IgEprevents airway remodeling in a murine model ofchronic asthma. Am J Respir Crit Care Med.2010;A1070. https://doi.org/10.1164/ajrccm-conference.2010.181.1_MeetingAbstracts.A1070
• 13.Kang JY, Kim JW, Kim JS, et al. Inhibitory effects ofanti-immunoglobulin E antibodies on airwayremodeling in a murine model of chronic asthma. JAsthma. 2010;47(4):374-380.https://doi.org/10.3109/02770901003801972
• 14.Fanni D, Gerosa C, Nurchi VM, et al. The role ofmagnesium in pregnancy and in fetal programming ofadult diseases. Biol Trace Elem Res.2021;199(11):3647-3657.https://doi.org/10.1007/s12011-020-02513-0
• 15.Ciosek Ż, Kot K, Kosik-Bogacka D, Łanocha-Arendarczyk N, Rotter I. The effects of calcium,magnesium, phosphorus, fluoride, and lead on bonetissue. Biomolecules. 2021;11(4):506. https://doi.org/10.3390/biom11040506
• 16.Mathew AA, Panonnummal R. ‘Magnesium’-themaster cation-as a drug-possibilities and evidences.Biometals. 2021;34(6):955-986.https://doi.org/10.1007/s10534-021-00328-7
• 17.Gaffney-Stomberg E. The impact of trace mineralson bone metabolism. Biol Trace Elem Res.2019;188(1):26-34. https://doi.org/10.1007/s12011-018-1583-8
• 18.Galli S, Stocchero M, Andersson M, et al. The effectof magnesium on early osseointegration inosteoporotic bone: a histological and gene expressioninvestigation. Osteoporos Int. 2017;28:2195-2205.https://doi.org/10.1007/s00198-017-4004-5
• 19.Cazzola R, Della Porta M, Manoni M, et al. Going tothe roots of reduced magnesium dietary intake: Atradeoff between climate changes and sources.Heliyon. 2020;6(11):e05390.https://doi.org/10.1016/j.heliyon.2020.e05390
• 20.Çetin İ, Nalbantcilar MT, İnci R, et al. Correlation ofdrinking water nutritional element levels with bodycomposition of women aged 55-70 years living inBatman province. Dicle Tıp Dergisi. 2017;44(1):99-108.
• 21. Oh JY, Lee YS, Min KH, et al. Osteoporosis in patients with asthma-chronic obstructive pulmonary diseaseoverlap syndrome. Tuberc Respir Dis (Seoul).2018;81(1):73-9.https://doi.org/10.4046/trd.2017.0066
• 22.van Niekerk G, Mitchell M, Engelbrecht AM. Boneresorption: supporting immunometabolism. Biol Lett.2018;14(2):20170783.
• 23.Zhang T, Yao Y. Effects of inflammatory cytokineson bone/cartilage repair. J Cell Biochem.2019;120(5):6841-50.
• 24.Wang X, Yan S, Liu C, et al. Fracture risk and bonemineral density levels in patients with systemic lupuserythematosus: a systematic review and meta-analysis. Osteoporos Int. 2016;27(5):1413-1423.https://doi.org/10.1007/s00198-015-3449-7
• 25.Michaeloudes C, Abubakar-Waziri H, Lakhdar R, etal. Molecular mechanisms of oxidative stress inasthma. Mol Aspects Med. 2022;85:101026.https://doi.org/10.1016/j.mam.2021.101026
• 26.O'Byrne P, Fabbri LM, Pavord ID, et al. Asthmaprogression and mortality: the role of inhaledcorticosteroids. Eur Respir J. 2019;54(1):1900491.https://doi.org/10.1183/13993003.00491-2019
• 27.Ragnoli B, Morjaria J, Pignatti P, et al. Dupilumaband tezepelumab in severe refractory asthma: newopportunities. Ther Adv Chronic Dis.2022;13:20406223221097327.https://doi.org/10.1177/20406223221097327
• 28.Menzella F, Fontana M, Galeone C, et al. A real-world evaluation of clinical outcomes of biologicalsand bronchial thermoplasty for severe refractoryasthma (BIOTERM). J Asthma Allergy. 2021;14:1019-1031. https://doi.org/10.2147/JAA.S324099
• 29. Stokes J. Anti-IgE treatment for disorders other than asthma. Front Med. 2017;4:152.https://doi.org/10.3389/fmed.2017.00152