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砷和铜在肾脏皮质中的蓄积与慢性砷摄入后生理和组织学改变的关系。

Association between As and Cu renal cortex accumulation and physiological and histological alterations after chronic arsenic intake.

机构信息

Instituto de Biología Celular, Facultad de Ciencias Médicas (FCM), Universidad Nacional de Córdoba (UNC), Ciudad Universitaria, Córdoba, Argentina.

出版信息

Environ Res. 2010 Jul;110(5):417-23. doi: 10.1016/j.envres.2009.09.002. Epub 2010 Feb 18.

DOI:10.1016/j.envres.2009.09.002
PMID:20170908
Abstract

Arsenic (As) is one of the most abundant hazards in the environment and it is a human carcinogen. Related to excretory functions, the kidneys in humans, animal models or naturally exposed fauna, are target organs for As accumulation and deleterious effects. Previous studies carried out using X-ray fluorescence spectrometry by synchrotron radiation (SR-microXRF) showed a high concentration of As in the renal cortex of chronically exposed rats, suggesting that this is a suitable model for studies on renal As accumulation. This accumulation was accompanied by a significant increase in copper (Cu) concentration. The present study focused on the localization of these elements in the renal cortex and their correlation with physiological and histological As-related renal effects. Experiments were performed on nine male Wistar rats, divided into three experimental groups. Two groups received 100 microg/ml sodium arsenite in drinking water for 60 and 120 consecutive days, respectively. The control group received water without sodium arsenite (< 50 ppb As). For histological analysis, 5-mum-thick sections of kidneys were stained with hematoxylin and eosin. Biochemical analyses were used to determine concentrations of plasma urea and creatinine. The As and Cu mapping were carried out by SR-microXRF using a collimated white synchrotron spectrum (300 microm x 300 microm) on kidney slices (2 mm thick) showing As and Cu co-distribution in the renal cortex. Then, renal cortical slices (100 microm thick) were scanned with a focused white synchrotron spectrum (30 microm x 30 microm). Peri-glomerular accumulation of As and Cu at 60 and 120 days was found. The effects of 60 days of arsenic consumption were seen in a decreased Bowman's space as well as a decreased plasma blood urea nitrogen (BUN)/creatinine ratio. Major deleterious effects; however, were seen on tubules at 120 days of exposition. This study supports the hypothesis that tubular accumulation of As-Cu may have some bearing on the arsenic-associated nephrotoxicological process.

摘要

砷(As)是环境中最丰富的危害之一,也是一种人类致癌物。与排泄功能有关,人类、动物模型或自然暴露的动物的肾脏是砷积累和有害影响的靶器官。先前使用同步辐射(SR-微 XRF)的 X 射线荧光光谱法进行的研究表明,慢性暴露的大鼠肾皮质中砷浓度很高,这表明这是研究肾砷积累的合适模型。这种积累伴随着铜(Cu)浓度的显著增加。本研究集中于肾皮质中这些元素的定位及其与生理和组织学砷相关肾效应的相关性。实验在 9 只雄性 Wistar 大鼠上进行,分为三组。两组分别连续 60 天和 120 天饮用含 100μg/ml 亚砷酸钠的水,对照组饮用不含亚砷酸钠的水(<50ppbAs)。用于组织学分析的肾组织切片厚度为 5μm,用苏木精和曙红染色。生化分析用于测定血浆尿素和肌酐的浓度。使用 SR-微 XRF 对肾切片(2mm 厚)进行 As 和 Cu 映射,该方法使用准直白光同步辐射光谱(300μm×300μm),结果显示 As 和 Cu 在肾皮质中的共同分布。然后,用聚焦白光同步辐射光谱(30μm×30μm)扫描肾皮质切片(100μm 厚)。在 60 天和 120 天观察到肾小球周围的 As 和 Cu 积累。在 60 天的砷消耗期间,观察到 Bowman 空间减少以及血浆血尿素氮(BUN)/肌酐比值降低。然而,在 120 天的暴露期间,肾小管受到了严重的损害。本研究支持这样一种假设,即 As-Cu 的肾小管积累可能与砷相关的肾毒性过程有关。

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