Disposition of methylmercury over time in a 75% nephrectomized rat model.
Disposition of methylmercury over time in a 75% nephrectomized rat model.
复制标题
处置%20of%20甲基汞%20over%20time%20in%20a%2075%%20肾切除%20rat%20模型。
DOI：
10.1080/15287394.2018.1443859
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Bridges,ChristyC
中科院分区：
文献类型：
--
作者：
Orr,SarahE;Joshee,Lucy;Barkin,Jennifer;Bridges,ChristyC
慢性肾脏病（CKD）是一种高度相关的临床疾病，其特征是功能性肾单位的永久性丧失。慢性肾病患者可能表现出肾脏清除功能受损，这可能会改变代谢物和异生物质的体内处理。甲基汞 (MeHg) 是人类经常接触的一种重要环境毒物。鉴于 CKD 的患病率以及环境中普遍存在的甲基汞，了解如何处理 CKD 患者体内的汞离子非常重要。因此，本研究的目的是表征 CKD 大鼠模型（即 75% 肾切除 (NPX) 大鼠）中甲基汞随时间的处置情况。对照和 NPX 大鼠每天一次静脉注射 (iv) 接触非肾毒性剂量的 MeHg (5 mg/kg)，持续 1、2 或 3 天，并测定器官、血液、尿液和粪便中的 MeHg 含量。对照动物的肾脏和血液中甲基汞的积累显着高于 NPX 动物。相比之下，对照组大脑和肝脏中的甲基汞水平与相应的 NPX 大鼠没有显着差异。在所有检查的器官中，甲基汞的积累随着暴露过程的增加而增加，这表明尿液和粪便的消除不足以完全消除所有汞离子。目前的发现很重要，因为长期暴露于甲基汞后，肾功能正常的大鼠与肾功能不全的大鼠中汞离子的处置不同，需要在治疗管理方面予以考虑。
Chronic kidney disease (CKD) is a highly relevant clinical condition that is characterized by the permanent loss of functional nephrons. Individuals with CKD may exhibit impaired renal clearance, which may alter corporal handling of metabolites and xenobiotics. Methylmercury (MeHg) is an important environmental toxicant to which humans are exposed to on a regular basis. Given the prevalence of CKD and ubiquitous presence of MeHg in the environment, it is important to understand how mercuric ions are handled in patients with CKD. Therefore, the purpose of the current study was to characterize the disposition of MeHg over time in a rat model of CKD (i.e., 75% nephrectomized (NPX) rats). Control and NPX rats were exposed intravenously (iv) to a non-nephrotoxic dose of MeHg (5 mg/kg) once daily for1, 2, or 3 d and the amount of MeHg in organs, blood, urine, and feces determined. The accumulation of MeHg in kidneys and blood of controls was significantly greater than that of NPX animals. In contrast, MeHg levels in brain and liver of controls were not markedly different from corresponding NPX rats. In all organs examined, accumulation of MeHg increased over the course of exposure, suggesting that urinary and fecal elimination are not sufficient to fully eliminate all mercuric ions. The current findings are important in that the disposition of mercuric ions in rats with normal renal function versus renal insufficiency following exposure to MeHg for a prolonged period differ and need to be taken into account with respect to therapeutic management.