Bagchi D, Bagchi M, Hassoun E A, Stohs S J
Department of Pharmaceutical and Administrative Sciences, School of Pharmacy and Allied Health Professions, Creighton University, Omaha, NE 68178, USA.
Biol Trace Elem Res. 1996 May;52(2):143-54. doi: 10.1007/BF02789456.
Recent studies have described lipid peroxidation to be an early and sensitive consequence of cadmium exposure, and free radical scavengers and antioxidants have been reported to attenuate cadmium-induced toxicity. These observations suggest that cadmium produces reactive oxygen species that may mediate many of the untoward effects of cadmium. Therefore, the effects of cadmium (II) chloride on reactive oxygen species production were examined following a single oral exposure (0.50 LD50) by assessing hepatic mitochondrial and microsomal lipid peroxidation, glutathione content in the liver, excretion of urinary lipid metabolites, and the incidence of hepatic nuclear DNA damage. Increases in lipid peroxidation of 4.0- and 4.2-fold occurred in hepatic mitochondria and microsomes, respectively, 48 h after the oral administration of 44 mg cadmium (II) chloride/kg, while a 65% decrease in glutathione content was observed in the liver. The urinary excretion of malondialdehyde (MDA), formaldehyde (FA), acetaldehyde (ACT), and acetone (ACON) were determined at 0-96 h after Cd administration. Between 48 and 72 h posttreatment maximal excretion of the four urinary lipid metabolites was observed with increases of 2.2- to 3.6-fold in cadmium (II) chloride-treated rats. Increases in DNA single-strand breaks of 1.7-fold were observed 48 h after administration of cadmium. These results support the hypothesis that cadmium induces production of reactive oxygen species, which may contribute to the tissue-damaging effects of this metal ion.
近期研究表明，脂质过氧化是镉暴露早期且敏感的后果，据报道自由基清除剂和抗氧化剂可减轻镉诱导的毒性。这些观察结果表明，镉会产生活性氧，可能介导镉的许多不良影响。因此，通过评估肝脏线粒体和微粒体脂质过氧化、肝脏中谷胱甘肽含量、尿脂质代谢产物排泄以及肝细胞核DNA损伤发生率，研究了单次口服暴露（0.50 LD50）后氯化镉（II）对活性氧产生的影响。口服44 mg氯化镉（II）/kg后48小时，肝脏线粒体和微粒体中的脂质过氧化分别增加了4.0倍和4.2倍，而肝脏中的谷胱甘肽含量下降了65%。在给予镉后0至96小时测定尿中丙二醛（MDA）、甲醛（FA）、乙醛（ACT）和丙酮（ACON）的排泄情况。在处理后48至72小时，观察到四种尿脂质代谢产物的排泄量达到最大值，氯化镉（II）处理的大鼠增加了2.2至3.6倍。给予镉后48小时，观察到DNA单链断裂增加了1.7倍。这些结果支持了镉诱导活性氧产生的假设，这可能导致这种金属离子的组织损伤作用。
