Abnormal auditory brainstem responses for mice treated with mercurial compounds: involvement of excessive nitric oxide
Abnormal auditory brainstem responses for mice treated with mercurial compounds: involvement of excessive nitric oxide
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DOI：
10.1016/s0300-483x(01)00348-1
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发表时间：
2001-04-12
期刊：
影响因子：
4.5
通讯作者：
Lin-Shiau, SY
中科院分区：
文献类型：
--
作者：
Chuu, JJ;Hsu, CJ;Lin-Shiau, SY
在本文中，我们试图建立一种监测硫化汞耳神经毒性的动物(小鼠)模型，并将其毒性与众所周知的(有机)汞化合物甲基汞进行比较。分别给予硫化汞(HGS，0.1和1.0g/kg/d)或甲基汞(MeHg，0.2，2.0和10 mg/kg/d)灌胃，连续7d。听性脑干反应(ABR)分析表明，甲基汞(2.0和0.2 mg/kg/d)或HGS-(1.0g/kg/d，而不是0.1g/kg/d)处理组小鼠的生理听阈显著提高，波间潜伏期I-V显著延长。此外，甲基汞和汞处理的动物都显示出显著的波间潜伏期I-V的延长，该潜伏期随着平均血汞水平的增加而增加。甲基汞(2.0 mg/kg/d)的耳神经毒性在停药后至少持续11周。停药5周后，HGS的毒性作用完全消失。这些结果表明汞引起的听力障碍与脑组织中汞的有效性之间存在相关性。脑干Na+/K+-ATPase活性的抑制和一氧化氮的过量产生都与对整个实验过程中各个时间点的生理听阈和ABR波形潜伏期的分析相一致。因此，有人认为大剂量汞或甲基汞中毒与脑干Na+/K+-ATPase活性降低有关，这可能是由过量的一氧化氮产生引起的，并提示脑干损伤可能在汞致听力损失中起作用。(C)2001爱思唯尔爱尔兰科学有限公司。保留所有权利。
In this paper, we attempted to construct an animal (mouse) model for monitoring the oto-neurotoxicity of mercuric sulfide, comparing its toxicity with the well-known (organic) mercury compound methyl-mercury. Mice were treated with either mercuric sulfide (HgS, 0.1 and 1.0 g/kg per day) or methyl-mercury (MeHg, 0.2, 2.0 and 10 mg/kg per day) by gastric gavage for 7 consecutive days. Analysis of auditory brainstem response (ABR) indicated that significant elevation of the physiological hearing threshold as well as significant prolongation of interwave latency I-V was observed for MeHg - (2.0 and 0.2 mg/kg per day) or HgS - (1.0 g/kg per day, but not 0.1 g/kg per day) treated mice. Further, both MeHg- and HgS-treated animals demonstrated a significant prolongation of interwave latency I-V that increased with an increasing mean blood-Hg level. The oto-neurotoxicity of MeHg (2.0 mg/kg per day) persisted to at least 11 weeks subsequent to the cessation of its administration. The toxic effect of HgS, however, disappeared completely 5 weeks subsequent to the cessation of its administration. These results suggest a correlation between the Hg-elicited hearing dysfunction and the availability of mercury in brain tissue. Both inhibition of Na+/K+-ATPase activity and overproduction of nitric oxide in the brainstem are consistent with an analysis of the physiological hearing threshold and latencies of ABR waveform at all time points throughout the experimental process. Thus, it is proposed that high-dose HgS or MeHg intoxication is associated with a decrease in functional Na+/K+-ATPase activity in the brainstem of affected animals, this presumably arising via excessive nitric oxide production, and suggesting that brainstem damage may play a role in mercury-induced hearing loss. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.