Link G, Athias P, Grynberg A, Pinson A, Hershko C
Department of Nutrition, Hebrew University Hadassah Medical School, Jerusalem, Israel.
J Lab Clin Med. 1989 Jan;113(1):103-11.
The effect of iron loading on membrane potential and cellular contractility was examined in cultured heart cells obtained from newborn rat ventricles exposed to ferric ammonium citrate at iron concentrations of 20, 40, and 80 micrograms/ml for 24 hours. The main functional effect of iron loading was depression of the overshoot potential. Severe arrhythmias were encountered in two of eight studies with 40 micrograms/ml iron and in two of seven studies with 80 micrograms/ml iron, but they were not found in any of the 29 control studies (p less than 0.01). Iron loading also resulted in a significant enhancement of cellular LDH release, indicating a loss of cell membrane integrity. In vitro treatment of iron-loaded cells with deferoxamine, a selective iron-chelating compound, resulted in a striking reversal of the iron-induced depression in the plateau phase of action potential, the disappearance of arrhythmias, and a reduction in LDH leakage. These favorable effects of deferoxamine lend support to the contention that the observed abnormalities following iron-loading were specific expressions of iron toxicity. Although these observations are consistent with iron-induced peroxidative damage to membrane lipid components, further studies are required in order to elucidate the nature of such a putative membrane effect of excess iron.
研究了铁负荷对从新生大鼠心室获取的培养心肌细胞的膜电位和细胞收缩性的影响。将这些细胞暴露于浓度为20、40和80微克/毫升的柠檬酸铁铵中24小时。铁负荷的主要功能影响是超射电位降低。在8项使用40微克/毫升铁的研究中有2项以及7项使用80微克/毫升铁的研究中有2项出现了严重心律失常，但在29项对照研究中均未发现（P<0.01）。铁负荷还导致细胞乳酸脱氢酶（LDH）释放显著增加，表明细胞膜完整性丧失。用选择性铁螯合剂去铁胺对铁负荷细胞进行体外处理，导致铁诱导的动作电位平台期降低明显逆转、心律失常消失以及LDH泄漏减少。去铁胺的这些有利作用支持了以下观点，即铁负荷后观察到的异常是铁毒性的特异性表现。尽管这些观察结果与铁诱导的膜脂质成分过氧化损伤一致，但为了阐明过量铁的这种假定膜效应的性质，还需要进一步研究。
