LLC-PK1 cells as a model for renal toxicity caused by arsine exposure.
LLC-PK1 cells as a model for renal toxicity caused by arsine exposure.
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LLC-PK1 细胞作为砷化氢暴露引起的肾毒性模型。
DOI：
10.1080/009841000156592
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Carter,DE
中科院分区：
文献类型：
--
作者：
Ayala-Fierro,F;Carter,DE
砷(AsH3)的毒性机制尚不完全清楚。研究了AsH3和亚砷酸盐[As(III)]对肾小管上皮细胞系的毒性，以模拟AsH3暴露引起的肾功能障碍。假设As(III)是导致AsH3肾毒性的有毒代谢物。As(III)孵育后呈现出浓度和时间依赖性的毒性反应。As(III)作用1h即可引起乳酸脱氢酶漏出，5h后细胞内钾离子丢失，而AsH3对上述参数无明显影响。AsH3在24 h内和1 mMAsH3浓度下均不影响钾和乳酸脱氢酶水平。在该体系中，As(III)在K+流失前引起LDH泄漏。通过测定谷胱甘肽(GSH)、谷胱甘肽二硫化物(GSSG)和热休克蛋白32(Hsp32)的水平，研究了氧化应激样毒性效应。GSH水平在6小时内不受任何砷的显著影响，或在高达100微米的砷浓度范围内。100µMAsH3作用30min后GSSG水平显著升高，2.5h达到最大值，10µMAsH3孵育足以显著提高GSSG水平。As(III)对GSSG无明显影响。两种砷化合物(50微米)孵育4小时后，Hsp32水平均略有增加(约3倍)。这些结果表明，未改变的AsH3产生了氧化应激样毒性效应，而不会导致细胞死亡。然而，与As(III)相似的浓度诱导了应激反应，并对细胞产生了毒性。提示AsH3对LLC-PK1细胞无直接毒性。
The mechanisms of arsine (AsH3) toxicity are not completely understood. Studies were undertaken to determine AsH3and arsenite [As(III)] toxicity in a renal tubular epithelial cell line to model kidney dysfunction caused by AsH3exposure. The hypothesis was that As(III) is the toxic metabolite responsible for the renal toxicity of AsH3. There was a concentration- and time-dependent toxic response after As(III) incubation. As(III) produced significant LDH leakage as early as 1 h and intracellular potassium loss at 5 h. AsH3produced no changes in these parameters. AsH3affected neither potassium nor LDH levels over 24 h and up to 1 mMAsH3concentration. In this system, As(III) induced LDH leakage before K+ loss. Oxidative stress-like toxicity effects were also studied by determining levels of glutathione (GSH), glutathione disulfide (GSSG), and heat-shock protein 32 (Hsp32) levels. GSH levels were not markedly affected by any arsenical over a 6-h period or up to 100 µMconcentration of the arsenical. However, 100 µMAsH3significantly increased GSSG levels as early as 30 min and reached a maximum at 2.5 h. Incubation with 10 µMAsH3was sufficient to significantly increase GSSG levels. As(III) had no marked effect on GSSG. Both arsenicals (50 µM) produced a slight increase (about threefold) in Hsp32 levels after 4-h incubation. These results showed that unchanged AsH3produced oxidative stress-like toxic effects without producing cell death. However, similar As(III) concentrations induced the stress response and were toxic to the cells. These data indicated that AsH3is not directly toxic to LLC-PK1cells.