Department of Physiological Sciences, Federal University of Espírito Santo, Av. Marechal Campos, 1468, Maruípe, Vitória, Espirito Santo, 29042-755, Brazil.
Department of Morphology/CCS, Federal University of Espírito Santo, Av. Marechal Campos, 1468, Maruípe, Vitória, Espirito Santo, 290440-090, Brazil.
Environ Sci Pollut Res Int. 2017 Nov;24(31):24509-24520. doi: 10.1007/s11356-017-0061-8. Epub 2017 Sep 13.
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. 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 N-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 E 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.
有机锡化合物，如三丁基锡（TBT），是环境污染物，会导致生物蓄积，并对海洋物种和哺乳动物产生潜在的毒性影响。国际海事组织已于 2003 年禁止使用 TBT。然而，对海洋沉积物中丁基锡和金属含量的评估表明，在某些情况下，TBT 的残留水平仍然很高，超过 7000ngSn/g。世界卫生组织确定的 TBT 每日允许摄入量（ADI）水平为 0.5μg/kg bw/day，这是基于遗传毒性、生殖毒性、致畸性、免疫毒性，主要是神经毒性。然而，它们对心血管系统的影响尚不清楚。在这项研究中，雌性大鼠每天接受 0.5μg/kg/day 的 TBT 暴露 15 天，旨在了解 TBT 对血管功能的影响。雌性 Wistar 大鼠通过灌胃每天接受治疗，并分为对照组（n=10）和 TBT 组（n=10）。在存在和不存在内皮的情况下，用苯肾上腺素孵育主动脉环。通过向内皮完整的样本中加入 N-硝基-L-精氨酸甲酯（L-NAME）、阿朴肉桂醇、超氧化物歧化酶（SOD）、过氧化氢酶、钛铁试剂和别嘌呤醇，生成苯肾上腺素浓度-反应曲线。乙酰胆碱（ACh）和硝普钠（SNP）用于评估舒张反应。暴露于 TBT 会降低血清 17β-雌二醇 E 水平并增加血管反应性。在用 L-NAME 孵育后，TBT 处理大鼠对苯肾上腺素的血管反应性显著增加。阿朴肉桂醇、SOD、过氧化氢酶和钛铁试剂显著降低了 TBT 处理大鼠对苯肾上腺素的血管反应性。TBT 大鼠诱导的 ACh 和 SNP 舒张反应明显降低。暴露于 TBT 诱导主动脉壁萎缩，并增加超氧阴离子产生和胶原沉积。这些结果表明，将大鼠暴露于当前 TBT 的 ADI（0.5μg/kg）15 天会导致氧化应激和形态损伤引起的血管功能障碍，应被视为一个重要的心血管危险因素。
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