Muldoon D F, Hassoun E A, Stohs S J
Dept. of Pharmacology, Creighton University Health Sciences Center, Omaha, NE 68178, USA.
Res Commun Mol Pathol Pharmacol. 1996 Apr;92(1):107-18.
Ricin has been shown to induce oxidative stress in the livers of mice in vivo. These studies examined ricin-induced hepatic microsomal lipid peroxidation in mice, and the modulation thereof by iron and desferrioxamine. In addition, the studies investigated the production of superoxide anion by microsomes, mitochondria, and macrophages. Ricin (25 micrograms/kg, in vivo) increased microsomal lipid peroxidation by approximately 1.8-fold relative to control animals. This effect was abrogated by adding desferrioxamine to the microsomes. Fe2+ increased lipid peroxidation approximately 15-fold and 5-fold when added to microsomes from control and ricin-treated animals, respectively. Adding ricin to microsomes from control animals, however, decreased lipid peroxidation in a concentration-dependent manner. Desferrioxamine decreased lipid peroxidation by 47% and 64% in the absence and presence of ricin (5 micrograms/ml), respectively. Ricin, added to mitochondria from untreated animals decreased lipid peroxidation by 26% and 17% in the presence and absence of Fe2+, respectively. The administration of ricin (5 and 25 micrograms/kg) to mice increased microsomal, mitochondrial and macrophage superoxide anion production, in a dose-dependent fashion. The results suggest that iron mediated production of superoxide anion may be involved in the process of oxidative stress induced by ricin.
蓖麻毒素已被证实在体内可诱导小鼠肝脏产生氧化应激。这些研究检测了蓖麻毒素诱导的小鼠肝脏微粒体脂质过氧化作用,以及铁和去铁胺对其的调节作用。此外,这些研究还调查了微粒体、线粒体和巨噬细胞中超氧阴离子的产生情况。相对于对照动物,蓖麻毒素(体内剂量为25微克/千克)使微粒体脂质过氧化作用增加了约1.8倍。向微粒体中添加去铁胺可消除这种作用。当分别添加到对照动物和经蓖麻毒素处理的动物的微粒体中时,Fe2+使脂质过氧化作用分别增加了约15倍和5倍。然而,向对照动物的微粒体中添加蓖麻毒素会以浓度依赖的方式降低脂质过氧化作用。在不存在和存在蓖麻毒素(5微克/毫升)的情况下,去铁胺分别使脂质过氧化作用降低了47%和64%。向未经处理的动物的线粒体中添加蓖麻毒素,在存在和不存在Fe2+的情况下,分别使脂质过氧化作用降低了26%和17%。给小鼠注射蓖麻毒素(5和25微克/千克)会以剂量依赖的方式增加微粒体、线粒体和巨噬细胞中超氧阴离子的产生。结果表明,铁介导的超氧阴离子产生可能参与了蓖麻毒素诱导的氧化应激过程。