Glutathione has a more important role than metallothionein-I/II against inorganic mercury-induced acute renal toxicity
Glutathione has a more important role than metallothionein-I/II against inorganic mercury-induced acute renal toxicity
复制标题
DOI：
10.2131/jts.43.275
复制
发表时间：
2018-01-01
影响因子：
2
通讯作者：
Satoh, Masahiko
中科院分区：
文献类型：
--
作者：
Tokumoto, Maki;Lee, Jin-Yong;Satoh, Masahiko
无机汞是一种有害的重金属，会导致严重的肾脏损伤。谷氨酰胺（GSH）是由L-谷氨酸、甘氨酸和L-半胱氨酸组成的三肽，金属硫蛋白（MT）是富含半胱氨酸的金属结合蛋白，是无机汞肾毒性的重要生物保护因子。然而，GSH和MT之间的关系，以防止无机汞的肾毒性是未知的。我们研究了通过用L-BSO（L-Buthietamine-SR-sulfoximine）处理的GSH耗尽的小鼠和MT-I和MT-II基因缺失的MT-I/II缺失小鼠对无机汞（HgCl 2）的敏感性。在用HgCl 2（30 μ mol/kg）处理的野生型小鼠中未诱导肾损伤。在MT-I/II基因敲除小鼠中，HgCl 2在30 μ mol/kg剂量下诱导肾毒性，但在1.0 μ mol/kg剂量下未诱导肾毒性。注射HgCl 2（30 μ mol/kg）后，两种品系的所有GSH耗尽小鼠均死亡。GSH耗竭野生型小鼠用HgCl 2（1.0 μ mol/kg）处理后，出现了与MT-I/II缺失小鼠用HgCl 2（30 μ mol/kg）处理后相似的肾损伤。此外，HgCl 2（1.0 μ mol/kg）诱导的肾毒性在GSH耗尽MT-I/II null小鼠中比GSH耗尽野生型小鼠更严重。本研究发现GSH和MT-I/II在无机汞引起的严重肾损伤的解毒中协同发挥重要作用。此外，GSH可能作为一个主要的保护因素，对无机汞诱导的急性肾毒性，因为GSH耗尽的小鼠更敏感的无机汞比MT-I/II裸小鼠。
Inorganic mercury is a harmful heavy metal that causes severe kidney damage. Glutathione (GSH), a tripeptide comprising L-glutamic acid, glycine and L-cysteine, and metallothionein (MT), a cysteine-rich and metal-binding protein, are biologically important protective factors for renal toxicity by inorganic mercury. However, the relationship between GSH and MT for the prevention of renal toxicity by inorganic mercury is unknown. We examined the sensitivity of the mice depleted in GSH by treatment with L-Buthionine-SR-sulfoximine (L-BSO), and MT-I/II null mice genetically deleted for MT-I and MT-II, to inorganic mercury (HgCl2). Kidney damage was not induced in the wild-type mice treated with HgCl2 (30 mu mol/kg). In the MT-I/II null mice, renal toxicity was induced by HgCl2 at a dose of 30 mu mol/kg but not 1.0 mu mol/kg. All GSH-depleted mice of both strains were dead following the injection of HgCl2 (30 mu mol/kg). GSH-depleted wild-type mice treated with HgCl2 (1.0 mu mol/kg) developed kidney damage similar to MT-I/II null mice treated with HgCl2 (30 mu mol/kg). Moreover, renal toxicity induced by HgCl2 (1.0 mu mol/kg) was more severe in GSH-depleted MT-I/lI null mice compared with GSH-depleted wild-type mice. The present study found that GSH and MT-I/II play cooperatively an important role in the detoxification of severe kidney damage caused by inorganic mercury. In addition, GSH may act as a primary protective factor against inorganic mercury-induced acute renal toxicity, because GSH-depleted mice were more sensitive to inorganic mercury than MT-I/II null mice.