Cardier J E, Romano E, Soyano A
Department of Experimental Medicine, Venezuelan Institute for Scientific Research (IVIC), Caracas, Venezuela.
Immunopharmacol Immunotoxicol. 1995 Nov;17(4):705-17. doi: 10.3109/08923979509037190.
This study was undertaken to investigate the hypothesis that lipid peroxidation might be associated with immunological abnormalities in experimental hemosiderosis. The correlation between the degree of plasma and spleen lipid peroxidation with lymphocyte proliferative response and with the proportion of T lymphocyte subsets was studied in normal and iron overloaded male Sprague Dawley rats. The iron-loading protocol consisted of a total dose of iron-dextran (1.5 mg/Kg body weight) divided in daily i.m. injections over twenty consecutive days. Lipid peroxidation was measured by the thiobarbituric acid assay in plasma and in homogenates of spleen. Plasma lipid peroxide level increased rapidly after i.m. administration of iron-dextran and decreased sharply at 48 h after the last injection. Conversely, a progressive increase of lipid peroxidation in homogenates of spleen was observed in the course of the iron overload protocol, remaining high even at 50 days after initiation of iron-dextran injections. The increase of spleen lipid peroxide levels was associated with decreased lymphocyte proliferative response to Con A in iron overloaded rats. The addition of superoxide dismutase and catalase to lymphocyte cultures reversed the inhibition of the proliferative response, implicating reactive species of oxygen as the causative agents of these alterations. These effects may be related with the enhanced membrane and DNA damage occurring during intracellular and extracellular peroxidation. Negative correlations between helper/cytotoxic ratio and malondialdehyde levels were obtained in blood and spleen during iron administration. These results supports the hypothesis that lipid peroxidation plays a role in the immunological abnormalities observed in experimental hemosiderosis.
本研究旨在探讨脂质过氧化可能与实验性血色素沉着症免疫异常相关的假说。在正常和铁过载的雄性Sprague Dawley大鼠中，研究了血浆和脾脏脂质过氧化程度与淋巴细胞增殖反应以及T淋巴细胞亚群比例之间的相关性。铁负荷方案包括将右旋糖酐铁的总剂量（1.5毫克/千克体重）连续20天每日肌肉注射。通过硫代巴比妥酸测定法测量血浆和脾脏匀浆中的脂质过氧化。肌肉注射右旋糖酐铁后，血浆脂质过氧化物水平迅速升高，并在最后一次注射后48小时急剧下降。相反，在铁过载方案过程中，观察到脾脏匀浆中的脂质过氧化逐渐增加，即使在开始注射右旋糖酐铁后50天仍保持较高水平。铁过载大鼠脾脏脂质过氧化物水平的升高与淋巴细胞对刀豆蛋白A的增殖反应降低有关。向淋巴细胞培养物中添加超氧化物歧化酶和过氧化氢酶可逆转增殖反应的抑制，表明活性氧是这些改变的致病因素。这些影响可能与细胞内和细胞外过氧化过程中发生的膜和DNA损伤增强有关。在铁给药期间，血液和脾脏中辅助/细胞毒性比值与丙二醛水平呈负相关。这些结果支持脂质过氧化在实验性血色素沉着症中观察到的免疫异常中起作用的假说。
