Aging and the disposition and toxicity of mercury in rats.
Aging and the disposition and toxicity of mercury in rats.
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DOI：
10.1016/j.exger.2014.02.006
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发表时间：
2014-05
影响因子：
3.9
通讯作者：
Zalups RK
中科院分区：
文献类型：
--
作者：
Bridges CC;Joshee L;Zalups RK
继发于年龄相关性肾小球疾病的肾功能逐渐丧失，可损害肾脏有效清除血液中代谢废物和毒物的能力。此外，随着肾肿块的减少，功能性肾单位的细胞肥大。我们假设这些肾单位暴露于更高水平的肾毒性物质，如无机汞（Hg2+），因此被这些化合物中毒的风险增加。本研究的目的是表征衰老对年轻成年和老年Wistar大鼠Hg2+的处置和肾毒性的影响。配对组动物分别静脉注射0.5 μmol•kg−1无肾毒性剂量或2.5 μmol•kg−1肾毒性剂量的氯化汞（HgCl2）。两组老年大鼠的血浆肌酐和近端肾小管损伤的肾脏生物标志物均高于相应组的青年成年大鼠。组织学上，肾小球硬化、肾小管萎缩、间质炎症和纤维化是老年动物肾脏的显著特征。此外，在HgCl2肾毒性剂量处理的老年和幼年大鼠肾脏切片中，近端肾小管坏死，特别是沿内皮层和外髓质外条纹的直段坏死是一个显著特征。我们的研究结果表明：1)老龄大鼠整体肾功能明显受损，导致慢性肾功能不全；2)老龄大鼠体内HgCl2的分布与幼龄大鼠相比有明显改变。
Progressive loss of functioning nephrons, secondary to age-related glomerular disease, can impair the ability of the kidneys to effectively clear metabolic wastes and toxicants from blood. Additionally, as renal mass is diminished, cellular hypertrophy occurs in functional nephrons that remain. We hypothesize that these nephrons are exposed to greater levels of nephrotoxicants, such as inorganic mercury (Hg2+), and thus are at an increased risk of becoming intoxicated by these compounds. The purpose of the present study was to characterize the effects of aging on the disposition and renal toxicity of Hg2+ in young adult and aged Wistar rats. Paired groups of animals were injected (i.v.) with either a 0.5 μmol • kg−1 non-nephrotoxic or a 2.5 μmol • kg−1 nephrotoxic dose of mercuric chloride (HgCl2). Plasma creatinine and renal biomarkers of proximal tubular injury were greater in both groups of aged rats than in the corresponding groups of young adult rats. Histologically, evidence of glomerular sclerosis, tubular atrophy, interstitial inflammation and fibrosis were significant features of kidneys from aged animals. In addition, proximal tubular necrosis, especially along the straight segments in the inner cortex and outer stripe of the outer medulla was a prominent feature in the renal sections from both aged and young rats treated with the nephrotoxic dose of HgCl2. Our findings indicate 1) that overall renal function is significantly impaired in aged rats, resulting in chronic renal insufficiency and 2) the disposition of HgCl2 in aging rats is significantly altered compared to that of young rats.
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影响因子：
3.6
作者：
Ding, GH;Franki, N;Singhal, PC
通讯作者：
Singhal, PC
影响因子：
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