Exposure to low-dose barium by drinking water causes hearing loss in mice
Exposure to low-dose barium by drinking water causes hearing loss in mice
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DOI：
10.1016/j.neuro.2012.07.008
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发表时间：
2012-10-01
期刊：
影响因子：
3.4
通讯作者：
Kato, Masashi
中科院分区：
文献类型：
--
作者：
Ohgami, Nobutaka;Hori, Sohjiro;Kato, Masashi
目的：在日常生活中，我们通过饮用水和食物来不断摄取钡作为一种通用元素。暴露于高剂量的钡(100毫克/公斤/天)已被证明会导致生理损伤。通过血管灌流直接给内耳注射钡已被证明会导致内耳的生理损伤。然而，在活体内，口服低剂量钡对听力水平的毒性影响尚未阐明。本实验分析了口服低剂量钡对小鼠听力和内耳的毒性影响。实验设计：给野生型ICR小鼠灌胃低剂量的0.14和1.4 mg/kg/d的钡。这些剂量分别相当于和高于世卫组织基于健康的饮用水指南的限量水平(每L 0.7毫克)10倍。暴露2周后，用听性脑干反应测定听力水平，并对内耳进行形态学分析。染毒2个月后，采用电感耦合等离子体质谱检测小鼠体内钡的组织分布。结果：饮水中低剂量的钡可致小鼠严重听力损失。内耳包括内外毛细胞、血管纹和螺旋神经节神经元严重变性。用药组大鼠内耳中的钡含量显著高于对照组，而骨中的含量在两组间无显著差异。两组小鼠大脑、小脑、心脏、肝脏和肾脏等其他组织中的钡含量均很低。结论：我们的结果首次证实了低剂量饮水给药对小鼠内耳的特异性分布，导致了严重的耳毒性和内耳退变。(C)2012 Elsevier Inc.保留所有权利。
Purpose: We continuously ingest barium as a general element by drinking water and foods in our daily life. Exposure to high-dose barium (>100 mg/kg/day) has been shown to cause physiological impairments. Direct administration of barium to inner ears by vascular perfusion has been shown to cause physiological impairments in inner ears. However, the toxic influence of oral exposure to low-dose barium on hearing levels has not been clarified in vivo. We analyzed the toxic influence of oral exposure to low-dose barium on hearing levels and inner ears in mice.Experimental design: We orally administered barium at low doses of 0.14 and 1.4 mg/kg/day to wild-type ICR mice by drinking water. The doses are equivalent to and 10-fold higher than the limit level (0.7 mg/l) of WHO health-based guidelines for drinking water, respectively. After 2-week exposure, hearing levels were measured by auditory brain stem responses and inner ears were morphologically analyzed. After 2-month exposure, tissue distribution of barium was measured by inductively coupled plasma mass spectrometry.Results: Low-dose barium in drinking water caused severe hearing loss in mice. Inner ears including inner and outer hair cells, stria vascularis and spiral ganglion neurons showed severe degeneration. The Barium-administered group showed significantly higher levels of barium in inner ears than those in the control group, while barium levels in bone did not show a significant difference between the two groups. Barium levels in other tissues including the cerebrum, cerebellum, heart, liver and kidney were undetectably low in both groups.Conclusions: Our results demonstrate for the first time that low-dose barium administered by drinking water specifically distributes to inner ears resulting in severe ototoxicity with degeneration of inner ears in mice. (C) 2012 Elsevier Inc. All rights reserved.