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Cardiac changes in apoptosis, inflammation, oxidative stress, and nitric oxide system induced by prenatal and postnatal zinc deficiency in male and female rats

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Abstract

Purpose

Zinc restriction during fetal and postnatal development could program cardiovascular diseases in adulthood. The aim of this study was to determine the effects of zinc restriction during fetal life, lactation, and/or post-weaning growth on cardiac inflammation, apoptosis, oxidative stress, and nitric oxide system of male and female adult rats.

Methods

Wistar rats were fed a low- or a control zinc diet during pregnancy and up to weaning. Afterward, offspring were fed either a low- or a control zinc diet until 81 days of life. IL-6 and TNF-α levels, TUNEL assay, TGF-β1 expression, thiobarbituric acid-reactive substances that determine lipoperoxidation damage, NADPH oxidase-dependent superoxide anion production, antioxidant and nitric oxide synthase activity, mRNA and protein expression of endothelial nitric oxide synthase, and serine1177 phosphorylation isoform were determined in left ventricle.

Results

Zinc deficiency activated apoptotic and inflammatory processes and decreased TGF-β1 expression and nitric oxide synthase activity in cardiac tissue of both sexes. Male zinc-deficient rats showed no changes in endothelial nitric oxide synthase expression, but a lower serine1177 phosphorylation. Zinc deficiency induced an increase in antioxidant enzymes activity and no differences in lipoperoxidation products levels in males. Females were less sensitive to this deficiency exhibiting lower increase in apoptosis, lower decrease in expression of TGF-β1, and higher antioxidant and nitric oxide enzymes activities. A zinc-adequate diet during postnatal life reversed most of these mechanisms.

Conclusion

Prenatal and postnatal zinc deficiency induces alterations in cardiac apoptotic, inflammatory, oxidative, and nitric oxide pathways that could predispose the onset of cardiovascular diseases in adult life.

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Acknowledgements

We thank Daniela Cardelli Alcalde, Franco Brunello, Julieta Gondolesi, Agustina Castañon, Hector Fasoli, and Gabriela Noceti for technical assistance and Ana Borthwick for proofreading and language assistance. This study was supported by University of Buenos Aires: 2013/2015: 20020120200056; 2014/2017: 20020130100026BA. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET): 2011–2015; PIP-11220080101121; PIP-11220110100581.

Author contributions

MNG, FMGA, MED, GP, and LVJ involved in animal care and diet preparation. JET studied the immunohistochemistry of pro-inflammatory cytokines. FMGA, MED, and LVJ were responsible for the determination of cardiac oxidative stress. RE, MNG, FMGA, and LVJ assessed the cardiac NOS activity. MNG, ALT, and LVJ involved in cardiac eNOS mRNA expression by RT-qPCR. LVJ, GP, and AC studied cardiac eNOS, p-eNOS (Ser 1177), and TGF-β1 protein expression by Western blot analysis. LVJ, OP, and LG performed TUNEL assay. MNG, FMGA, LVJ, and ALT involved in NADPH oxidase-dependent superoxide anion production. CTA, RE, and ALT were responsible for experimental design, scientific and technical supervision, and analysis of results. LVJ, ALT, RE, and CTA drafted the manuscript.

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Authors and Affiliations

  1. Instituto de la Química y Metabolismo del Fármaco (IQUIMEFA). Facultad de Farmacia y Bioquímica, Cátedra de Fisiología, Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, 956, piso 7, 1113, Junín, Ciudad Autónoma de Buenos Aires, Argentina

    Lorena Vanesa Juriol, María Natalia Gobetto, Facundo Mendes Garrido Abregú, Marina Ercilia Dasso, Gonzalo Pineda, Rosana Elesgaray, Cristina Teresa Arranz & Analía Lorena Tomat

  2. Laboratorio de Terapia Molecular y Celular, Fundación Instituto Leloir, IIBBA-CONICET, Avenida Patricias Argentinas 435, 1405, Buenos Aires, Argentina

    Leandro Güttlein & Osvaldo Podhajcer

  3. Facultad de Farmacia y Bioquímica, Cátedra de Farmacología, Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, 956, piso 5, 1113, Junín, Ciudad Autónoma de Buenos Aires, Argentina

    Andrea Carranza

  4. Laboratorio Medicina Experimental, Hospital Alemán, Avenida Pueyrredón 1640, C1118 AAT, Buenos Aires, Argentina

    Jorge Eduardo Toblli

Authors
  1. Lorena Vanesa Juriol
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  2. María Natalia Gobetto
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  3. Facundo Mendes Garrido Abregú
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  12. Analía Lorena Tomat
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Correspondence to Analía Lorena Tomat.

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Juriol, L.V., Gobetto, M.N., Mendes Garrido Abregú, F. et al. Cardiac changes in apoptosis, inflammation, oxidative stress, and nitric oxide system induced by prenatal and postnatal zinc deficiency in male and female rats. Eur J Nutr 57, 569–583 (2018). https://doi.org/10.1007/s00394-016-1343-5

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