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Chronic Iron Overload Restrains the Benefits of Aerobic Exercise to the Vasculature

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Abstract

Physical exercise is a well-recognized effective non-pharmacological therapy for cardiovascular diseases. However, because iron is essential element in many physiological processes including hemoglobin and myoglobin synthesis, thereby playing a role on oxygen transport, many athletes use iron supplement to improve physical performance. Regarding this, iron overload is associated with oxidative stress and damage to various systems, including cardiovascular. Thus, we aimed to identify the vascular effects of aerobic exercise in a rat model of iron overload. Male Wistar rats were treated with 100 mg/kg/day iron-dextran, i.p., 5 days a week for 4 weeks, and then underwent aerobic exercise protocol on a treadmill at moderate intensity, 60 min/day, 5 days a week for 8 weeks. Exercise reduced vasoconstrictor response of isolated aortic rings by increasing participation of nitric oxide (NO) and reducing oxidative stress, but these benefits to the vasculature were not observed in rats previously subjected to iron overload. The reduced vasoconstriction in the exercised group was reversed by incubation with superoxide dismutase (SOD) inhibitor, suggesting that increased SOD activity by exercise was lost in iron overload rats. Iron overload groups increased serum levels of iron, transferrin saturation, and iron deposition in the liver, gastrocnemius muscle, and aorta, and the catalase was overexpressed in the aorta probably as a compensatory mechanism to the increased oxidative stress. In conclusion, despite the known beneficial effects of aerobic exercise on vasculature, our results indicate that previous iron overload impeded the anticontractile effect mediated by increased NO bioavailability and endogenous antioxidant response due to exercise protocol.

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Acknowledgments

The authors thank the technical support of the Multi-user Laboratory of Histotechniques (LHT) and Laboratory of Histology and Immunistochemistry (LHMI) for the use of the microscope for histological analysis and the Laboratory of Experimental Physiology and Biochemistry (LAFIBE) for the technical support in the use of the treadmill for rodents. Special acknowledgment is given to Mr. Charles G. Rees for assistance with language correction and style.

Funding

This work was supported by grants from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES—Finance code 001), Conselho Nacional de Desenvolvimento Científico e Tecnológico (grant numbers 433632/2018-6 MCTIC/CNPq 28-2018 and 303077/2017-4 CNPq 12-2017), and Fundação de Amparo à Pesquisa do Espírito Santo (grant number 80707483 Edital Universal FAPES 03/2017, and grant number 388/2018 Edital PROFIX).

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Authors and Affiliations

  1. Department of Physiological Sciences, Federal University of Espirito Santo, Av. Marechal Campos, 1468, Vitoria, ES, 29040-091, Brazil

    Emilly Martinelli Rossi, Renata Andrade Ávila, Camila C. P. Almenara & Leonardo dos Santos

  2. Faculdades Integradas São Pedro (FAESA), Av. Vitória, 2220, Vitoria, ES, 29053-360, Brazil

    Renata Andrade Ávila

  3. Department of Chemistry, Federal University of Espirito Santo, Av. Fernando Ferrari, 514, Vitoria, ES, 29075-910, Brazil

    Maria Tereza W. D. Carneiro

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  1. Emilly Martinelli Rossi
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  5. Leonardo dos Santos
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Correspondence to Leonardo dos Santos.

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All experiments were conducted in accordance with the Brazilian Guidelines for the Care and Use of Animals for Scientific and Educational Purposes, and the protocols were approved by the Institutional Ethics Committee on Animal Use (CEUA-UFES registration number 88/2015).

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Rossi, E.M., Ávila, R.A., Carneiro, M.T.W.D. et al. Chronic Iron Overload Restrains the Benefits of Aerobic Exercise to the Vasculature. Biol Trace Elem Res 198, 521–534 (2020). https://doi.org/10.1007/s12011-020-02078-y

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