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Tributyltin chloride disrupts aortic vascular reactivity and increases reactive oxygen species production in female rats

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Abstract

Organotin compounds, such as tributyltin (TBT), are environment contaminants that induce bioaccumulation and have potential toxic effects on marine species and mammals. TBT have been banned by the International Maritime Organization in 2003. However, the assessment of butyltin and metal contents in marine sediments has demonstrated high residual levels of TBT in some cases exceeding 7000 ng Sn g−1. The acceptable daily intake (ADI) level for TBT established by the World Health Organization is 0.5 μg/kg bw/day is based on genotoxicity, reproduction, teratogenicity, immunotoxicity, and mainly neurotoxicity. However, their effect on the cardiovascular system is not well understood. In this study, female rats were exposed to 0.5 μg/kg/day of TBT for 15 days with the goal of understanding the effect of TBT on vascular function. Female Wistar rats were treated daily by gavage and divided into control (n = 10) and TBT (n = 10) groups. The aortic rings were incubated with phenylephrine in both the presence and absence of endothelium. The phenylephrine concentration–response curves were generated by exposing endothelium-intact samples to NG-nitro-l-arginine methyl ester (L-NAME), apocynin, superoxide dismutase (SOD), catalase, tiron, and allopurinol. Acetylcholine (ACh) and sodium nitroprusside (SNP) were used to evaluate the relaxation response. Exposure to TBT reduced serum 17β-estradiol E2 levels and increased vascular reactivity. After incubation with L-NAME, the vascular reactivity to phenylephrine was significantly higher. Apocynin, SOD, catalase, and tiron decreased the vascular reactivity to phenylephrine to a significantly greater extent in TBT-treated rats than in the control rat. The relaxation induced by ACh and SNP was significantly reduced in TBT rats. Exposure to TBT induced aortic wall atrophy and increased superoxide anion production and collagen deposition. These results provide evidence that exposing rats to the current ADI for TBT (0.5 μg/kg) for 15 days induced vascular dysfunction due to oxidative stress and morphological damage and should be considered an important cardiovascular risk factor.

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Acknowledgements

This study was supported by “Coordenação de Aperfeiçoamento de Pessoal de Nível Superior” (CAPES), “Conselho Nacional de Desenvolvimento Científico e Tecnológico” (CNPq 201806/2015-0-455294/2014-3) and “Fundação de Amparo à Pesquisa do Espírito Santo” (FAPES no. 0609-2015) in Brazil. We thank the Laboratory of Cellular Ultrastructure-UFES (grant: MCT/FINEP/CT-INFRA—PROINFRA 01/2006) for the development of the SEM protocols; the Laboratory of Molecular Histology and Immunohistochemistry at UFES for the development of the DHE protocols; and the Laboratory of Biochemistry and Molecular Biophysics of Proteins at UFES for the development of the TBARS protocols. We thank Scott Holt for checking and improving the use of the English language in the manuscript.

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  1. Department of Physiological Sciences, Federal University of Espírito Santo, Av. Marechal Campos, 1468, Maruípe, Vitória, Espirito Santo, 29042-755, Brazil

    Carolina Falcão Ximenes, Samya Mere Lima Rodrigues, Lívia Carla Melo Rodrigues, Juliana Barbosa Coitinho, Dalton Valentim Vassallo & Ivanita Stefanon

  2. Department of Morphology/CCS, Federal University of Espírito Santo, Av. Marechal Campos, 1468, Maruípe, Vitória, Espirito Santo, 290440-090, Brazil

    Priscila Lang Podratz, Eduardo Merlo, Julia Fernandez Puñal de Araújo & Jones Bernardes Graceli

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  1. Carolina Falcão Ximenes
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  2. Samya Mere Lima Rodrigues
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Ximenes, C.F., Rodrigues, S.M.L., Podratz, P.L. et al. Tributyltin chloride disrupts aortic vascular reactivity and increases reactive oxygen species production in female rats. Environ Sci Pollut Res 24, 24509–24520 (2017). https://doi.org/10.1007/s11356-017-0061-8

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