Protective role of metallothionein in renal toxicity of cisplatinum
Protective role of metallothionein in renal toxicity of cisplatinum
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DOI：
10.1007/s002800050670
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发表时间：
1997-08-01
影响因子：
3
通讯作者：
Tohyama, C
中科院分区：
文献类型：
--
作者：
Satoh, M;Aoki, Y;Tohyama, C
为阐明金属硫蛋白（MT）在预防顺铂（cis-DDP）毒性中的保护作用，我们研究了cis-DDP对MT敲除转基因小鼠和野生型对照小鼠的致死毒性和肾毒性，并观察了硝酸铋或硫酸锌预处理对cis-DDP肾毒性的影响。MT敲除小鼠为129奥拉和C57 BL/6混合遗传背景。由于在这些品系之间未观察到顺式DDP肾毒性差异，因此使用C57 BL/6 J小鼠作为野生型对照。在MT缺失小鼠中肾脏中的基础MT水平可以忽略不计，在C57 BL/6 J小鼠中为2.93 +/- 0.77 μ g/g组织。在cis-DDP的致死毒性和肾毒性方面，MT-null小鼠远比C57 BL/6 J小鼠敏感。通过给予硝酸铋或硫酸锌预诱导肾脏MT合成保护C57 BL/6 J小鼠免受顺式DDP肾毒性。然而，在MT-null小鼠的情况下，肾MT不能诱导这些金属化合物的预处理，顺式DDP的肾毒性不能防止这种预处理。这些结果表明，MT是一个重要的因素，有可能抑制顺铂毒性的发展。
To elucidate the protective role of metallothionein (MT) in the prevention of cisplatinum (cis-DDP) toxicity, we investigated the lethal and renal toxicities caused by cis-DDP in MT-null transgenic mice in comparison with wild-type control mice, and examined the effect of pretreatment with bismuth nitrate or zinc sulfate on the cis-DDP nephrotoxicity. The MT-null mice were of mixed 129 Ola and C57BL/6 genetic background. Since no differences in cis-DDP nephrotoxicity were observed between these strains, C57BL/6J mice were used as the wild-type control. The basal MT levels in the kidneys were negligible in the MT-null mice and 2.93 +/- 0.77 mu g/g tissue in the C57BL/6J mice. In terms of both the lethal and renal toxicities of cis-DDP, MT-null mice were far more sensitive than C57BL/6J mice. Preinduction of renal MT synthesis by administration of bismuth nitrate or zinc sulfate protected C57BL/6J mice from cis-DDP nephrotoxicity. In the case of MT-null mice, however, renal MT could not be induced by pretreatment with these metal compounds, and renal toxicity of cis-DDP was not prevented by this pretreatment. These results suggest that MT is an important factor with the potential to suppress the development of cis-DDP toxicity.