Radiocontrast-induced renal tubular cell apoptosis - Hypertonic versus oxidative stress
Radiocontrast-induced renal tubular cell apoptosis - Hypertonic versus oxidative stress
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DOI：
10.1097/00004424-200208000-00003
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发表时间：
2002-08-01
影响因子：
6.7
通讯作者：
Haller, C
中科院分区：
文献类型：
--
作者：
Hizoh, I;Haller, C
理论基础和目标。造影剂肾病(RCIN)是血管内造影剂治疗的主要并发症。肾小管上皮细胞凋亡是RCIN的一个特征，这与造影剂的高张力有关。由于高渗细胞外环境通过活性氧诱导氧化应激，我们验证了抗氧化剂减少高渗诱导的肾上皮细胞凋亡的假说。我们分析了抗氧化剂N-乙酰半胱氨酸(NAC)和牛磺酸对高渗诱导的体外培养的肾上皮细胞凋亡的影响。方法：用高渗离子放射造影剂泛影葡胺(20%Vol/Voi，6h)或等渗(640mOsm/kg)的氯化钠溶液孵育大鼠肾小管上皮细胞。结果：泛影葡胺和氯化钠均可诱导MDCK细胞DNA片段化。牛磺酸(10 mmoL/L)抑制了泛影葡胺和氯化钠处理的细胞的DNA降解[分别为79.5+/-2.3%比72.2+/-3.0%；P=0.0088]和[49.5+/-4.0%比39.4+/-1.0%；P=0.0271]。结论：在高张诱导的肾小管细胞凋亡模型中，NAc(10 mmoL/L)不能减少DNA的断裂。牛磺酸可减弱高张/对比剂诱导的MDCK细胞DNA断裂，但NAC不能。因为这两种试剂都是抗氧化剂，抗氧化性不足以达到观察到的细胞保护作用。因此，牛磺酸的抗细胞凋亡作用必须归因于其他机制，但尚未明确。我们的结果表明，药理剂量的牛磺酸可能对RCIN具有特别的保护作用。
RATIONALE AND OBJECTIVES. Radiocontrast-induced nephropathy (RCIN) is a major complication of intravascular radiocontrast administration. Renal tubular cell apoptosis is a feature of RCIN, which is related to hypertonicity of contrast agents. Because a hyperosmolal extracellular environment induces oxidative stress via reactive oxygen species, we tested the hypothesis that antioxidants decrease hypertonicity-induced apoptosis of renal epithelial cells. We analyzed the effects of the antioxidants N-acetyleysteine (NAC) and taurine on hypertonicity -induced apoptosis of renal epithelial cells in vitro.METHODS. Madin Darby Canine Kidney (MDCK) cells were incubated with the highly hyperosmolal, ionic radiocontrast agent diatrizoate (20% vol/voI, 6 hours) or with equally hyperosmolal (640 mOsm/kg) NaCl solutions. DNA fragmentation, which is a hallmark feature of apoptosis, was assessed quantitatively using flow cytometry after propidium iodide staining and qualitatively using agarose gel electrophoresis.RESULTS. Both diatrizoate and NaCl induced DNA fragmentation in MDCK cells. Taurine (10 mmol/L) reduced DNA degradation in both diatrizoate- [79.5 +/- 2.3% versus 72.2 +/- 3.0%; P = 0.0088] and NaCl- [49.5+/- 4.0% versus 39.4 +/- 1.0%; P = 0.0271] treated cells. In contrast, NAC (10 mmol/L) failed to reduce the DNA breakdown in this model of hypertonicity -induced renal tubular cell apoptosis,CONCLUSIONS. The radiocontrast/hypertonicity-induced DNA fragmentation of MDCK cells is attenuated by taurine but not by NAC. Because both agents are antioxidants, the antioxidant property is not sufficient for the observed cytoprotective effect. Hence, the antiapoptotic effect of taurine has to be attributed to other, yet to be defined mechanisms. Our results suggest that pharmacological doses of taurine may be particularly protective against RCIN.