Breborowicz M, Polubinska A, Tam P, Wu G, Breborowicz A
Poznań Medical School, Poznań, Poland, Institute of Kidney Lifescience Technologies, Toronto, Canada.
Eur J Clin Invest. 2003 Dec;33(12):1038-44. doi: 10.1111/j.1365-2362.2003.01264.x.
Iron supplementation is often required in uraemic patients with anaemia. Peritoneal cavity was proposed as an alternative intravenous route for iron infusion in patients treated with peritoneal dialysis. We studied the effect of iron sucrose (Venofer) on the function of human peritoneal mesothelial cells maintained in in vitro culture.
In in vitro experiments on human peritoneal, the mesothelial effect of elemental iron (in conc. 0.0001-1 mg mL-1) present in Venofer on their viability, growth and synthesis of IL-6 was studied. Additionally we evaluated with a fluorescent probe (2',7'-dichlorodihydro-fluorescein diacatate) generation of reactive oxygen species in cells exposed to iron sucrose. We also measured accumulation of iron in the cytoplasm of mesothelial cells after their in vitro exposure to Venofer.
In in vitro conditions iron induces a dose-dependent inhibition of viability of the mesothelial cells as reflected by inhibition of the cells growth by 34% at Fe 0.1 mg mL-1 vs. control (P < 0.05) increased release of lactate dehydrogenase (LDH) from the cytosol: 67.1 +/- 30.3 mU mL-1 at Fe 1 mg mL-1 vs. 7.9 +/- 6.4 in control group (P < 0.001), and reduced synthesis of IL-6: 209 +/- 378 pg mg-1 cell protein at Fe 1 mg mL-1 vs. 38674 +/- 4146 pg mg-1 cell protein in controls (P < 0.001). Cytotoxicity of iron towards mesothelial cells was enhanced in vitro when it was tested in presence of the dialysis fluid. Iron used in vitro at concentration 0.0001 mg mL-1 and greater induces generation of oxygen-derived free radicals in mesothelial cells. Furthermore, iron is taken by these cells and stored in their cytosol, resulting in stimulation of the intracellular generation of free radicals.
We conclude that iron used in the form of iron sucrose is cytotoxic to human peritoneal mesothelial cells. Accumulation of iron sucrose within cytoplasm of these cells may lead to induction of its chronic cytotoxic effect.
尿毒症贫血患者常需补充铁剂。有人提出腹膜腔可作为腹膜透析患者静脉补铁的替代途径。我们研究了蔗糖铁（维乐福）对体外培养的人腹膜间皮细胞功能的影响。
在人腹膜体外实验中，研究了维乐福中元素铁（浓度为0.0001 - 1 mg/mL）对其活力、生长及白细胞介素-6合成的间皮效应。此外，我们用荧光探针（二氯二氢荧光素二乙酸酯）评估了暴露于蔗糖铁的细胞中活性氧的生成。我们还测量了间皮细胞在体外暴露于维乐福后铁在其细胞质中的蓄积情况。
在体外条件下，铁诱导间皮细胞活力呈剂量依赖性抑制，表现为在铁浓度为0.1 mg/mL时细胞生长受抑制34%，与对照组相比（P < 0.05），细胞溶质中乳酸脱氢酶（LDH）释放增加：铁浓度为1 mg/mL时为67.1±30.3 mU/mL，而对照组为7.9±6.4（P < 0.001），白细胞介素-6合成减少：铁浓度为1 mg/mL时为209±378 pg/mg细胞蛋白，而对照组为38674±4146 pg/mg细胞蛋白（P < 0.001）。当在透析液存在的情况下进行测试时，铁对间皮细胞的细胞毒性在体外增强。体外使用浓度为0.0001 mg/mL及更高的铁可诱导间皮细胞中氧衍生自由基的生成。此外，这些细胞摄取铁并将其储存在细胞质中，导致细胞内自由基生成增加。
我们得出结论，蔗糖铁形式的铁对人腹膜间皮细胞具有细胞毒性。这些细胞细胞质中蔗糖铁的蓄积可能导致其慢性细胞毒性作用的诱导。
