Link G, Pinson A, Kahane I, Hershko C
Department of Nutrition, Hebrew University Hadassah Medical School, Jerusalem, Israel.
J Lab Clin Med. 1989 Sep;114(3):243-9.
Increased generation of free radicals and accelerated lipid peroxidation are important manifestations of iron toxicity. We have studied the effect of iron loading on lipid peroxidation in cultured rat myocardial cells by direct measurement of the fatty acid composition of cellular lipids. Iron loading produced by 24-hour incubation of cultured cells with 0.36 mmol/L ferric ammonium citrate resulted in a moderate reduction in polyunsaturated fatty acids (PUFAs) such as 22:5 and 22:6. A more drastic reduction in PUFAs and an apparent reciprocal increase in the proportion of saturated fatty acids were both obtained after 24 hours of incubation of liposomal vesicles prepared from whole cell lipid extracts with iron at between pH 4.5 and pH 5.5. Reduction of 22:5 and 22:6 was first noticed at 3 hours, and undetectable levels were reached by 12 and 24 hours of incubation. Ascorbate had a biphasic effect on liposomal PUFA levels: at low concentrations (0.057 mmol/L) it enhanced the iron-induced changes in liposomal fatty acid composition, but at higher concentrations (0.57 and 5.7 mmol/L), it inhibited these changes. Unlike ascorbate, alpha-tocopherol (0.023 to 2.3 mmol/L) inhibited the iron-induced reduction in PUFAs in a dose-dependent manner, with complete inhibition of the iron effect at 2.3 mmol/L. These observations underline the particular sensitivity of PUFAs to iron-induced lipid peroxidation. They also illustrate the ability of ascorbate and alpha-tocopherol to modify iron-induced lipid peroxidation. Further studies are required to explore the possible therapeutic implications of these observations in clinical iron overload.
自由基生成增加和脂质过氧化加速是铁毒性的重要表现。我们通过直接测量细胞脂质的脂肪酸组成，研究了铁负荷对培养的大鼠心肌细胞脂质过氧化的影响。用0.36 mmol/L柠檬酸铁铵对培养细胞进行24小时孵育产生的铁负荷，导致多不饱和脂肪酸（PUFA）如22:5和22:6适度减少。用全细胞脂质提取物制备的脂质体囊泡在pH 4.5至pH 5.5之间与铁孵育24小时后，PUFA的减少更为显著，饱和脂肪酸的比例明显相应增加。22:5和22:6的减少在3小时时首次被注意到，孵育12小时和24小时后达到检测不到的水平。抗坏血酸对脂质体PUFA水平有双相作用：在低浓度（0.057 mmol/L）时，它增强了铁诱导的脂质体脂肪酸组成变化，但在较高浓度（0.57和5.7 mmol/L）时，它抑制了这些变化。与抗坏血酸不同，α-生育酚（0.023至2.3 mmol/L）以剂量依赖的方式抑制铁诱导的PUFA减少，在2.3 mmol/L时完全抑制铁的作用。这些观察结果强调了PUFA对铁诱导的脂质过氧化的特殊敏感性。它们还说明了抗坏血酸和α-生育酚改变铁诱导的脂质过氧化的能力。需要进一步研究以探索这些观察结果在临床铁过载中可能的治疗意义。
