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Oral methylmercury intoxication aggravates cardiovascular risk factors and accelerates atherosclerosis lesion development in ApoE knockout and C57BL/6 mice

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Abstract

Methylmercury (MeHg) intoxication is associated with hypertension, hypercholesterolemia, and atherosclerosis by mechanisms that are not yet fully understood. We investigated the effects of MeHg intoxication in atherosclerosis-prone (ApoE-KO) and resistant C57BL/6 mice. Mice were submitted to carotid stenosis surgery (to induce atherosclerosis faster) and received water or MeHg solution (20 mg/L) for 15 days. Tail plethysmography was performed before and after MeHg exposure. Food and MeHg solution intakes were monitored weekly. On the 15th day, mice were submitted to intravital fluorescence microscopy of mesenteric vasculature to observe in vivo leukocyte rolling and adhesion. Results showed that despite the high hair and liver Hg concentrations in the MeHg group, food and water (or MeHg solution) consumption and liver function marker levels were similar to those in controls. MeHg exposure increased total cholesterol, the atherogenic (non-HDL) fraction and systolic and diastolic blood pressure. MeHg exposure also induced inflammation, as seen by the increased rolling and adhered leukocytes in the mesenteric vasculature. Atherosclerosis lesions were more extensive in the aorta and carotid sites of MeHg-ApoE knockout mice. Surprisingly, MeHg exposure also induced atherosclerosis lesions in C57BL/6 mice, which are resistant to atherosclerosis formation. We concluded that MeHg intoxication might represent a risk for cardiovascular diseases since it accelerates atherogenesis by exacerbating several independent risk factors.

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Fig. 1
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Source of variation for lesion area: treatment: p = 0.16; strain: p = 0.02; interaction: p = 0.70. Source of variation for stenosis (%): treatment: p = 0.008; strain: p < 0.0001; interaction: p = 0.42. Different letters represent statistically significant differences between groups obtained by 2-way ANOVA, and * represents the difference as analyzed by unpaired Student t-test. WT n = 10; WTHg n = 10; APO n = 11; APOHg n = 12

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Acknowledgements

The authors acknowledge the financial support of the Brazilian National Council for Scientific and Technological Development (CNPq), Coordination for the Improvement of Higher Education Personnel (CAPES) PROCAD 88881.068408/2014-01. The authors also thank the Image Acquisition and Processing Center (CAPI—ICB/UFMG) for the use of imaging equipment.

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Authors and Affiliations

  1. Departamento de Bioquímica e Imunologia ICB/UFMG Caixa Postal 486, Belo Horizonte, MG, CEP 30161-970, Brazil

    Janayne L. Silva, Jonas M. Reis & Jacqueline I. Alvarez-Leite

  2. Departamento de Nutrição e Saúde, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

    Paola C. L. Leocádio

  3. Departamento de Fisiologia e Biofísica, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

    Gianne P. Campos & Luciano S. A. Capettini

  4. Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

    Giselle Foureaux & Anderson J. Ferreira

  5. Departamento de Química, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

    Cláudia C. Windmöller

  6. Departamento de Morfologia, Universidade Federal Do Ceará, Fortaleza, Ceará, Brazil

    Flávia A. Santos & Reinaldo B. Oriá

  7. Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, Pará, Brazil

    Maria E. Crespo-López

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Silva, J.L., Leocádio, P.C.L., Reis, J.M. et al. Oral methylmercury intoxication aggravates cardiovascular risk factors and accelerates atherosclerosis lesion development in ApoE knockout and C57BL/6 mice. Toxicol Res. 37, 311–321 (2021). https://doi.org/10.1007/s43188-020-00066-x

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