Goyer R A, Cherian M G, Delaquerriere-Richardson L
J Environ Pathol Toxicol Oncol. 1984 Jul;5(4-5):89-100.
Rats were injected daily, five days/week, with 0.6 mg Cd/kg as CdCl2 for eight weeks. Groups of rats were sacrificed weekly. Urine, plasma and tissue cadmium levels, and morphology of renal cortex were studied. No abnormal effects were found until the fifth or sixth week when cadmium in kidney reached about 100 micrograms/g tissue. At this time, renal tubular lining cells showed an increase in lysosomes, microbodies and smooth endoplasmic reticulum and a low molecular weight cadmium-binding species was detectable in plasma. These changes were followed by the onset of glycosuria and proteinuria, accompanied by abnormal mitochondrial morphology. This progressed to cellular swelling and finally necrosis at the seventh and eighth weeks when cadmium concentration of the kidney reached about 200 micrograms/g of tissue. It is concluded that there are two phases in the development of cadmium induced nephropathy. Phase I is an adaptive phase characterized by some increase in smooth endoplasmic reticulum, microbodies and secondary lysosomes and the presence of metallothionein intracellularly in liver and kidney, but no detectable metallothionein in plasma and no increase in urinary cadmium. Phase II is a toxic phase characterized by detectable low molecular weight cadmium-binding species in plasma and evidence of renal tubular dysfunction followed by lethal injury to renal tubular lining cells.
大鼠每周五天，每天注射0.6毫克/千克氯化镉形式的镉，持续八周。每周处死一组大鼠。研究尿液、血浆和组织中的镉水平以及肾皮质的形态。直到第五或六周，肾脏中的镉达到约100微克/克组织时才发现异常影响。此时，肾小管内衬细胞的溶酶体、微体和平滑内质网增加，血浆中可检测到一种低分子量镉结合物质。这些变化之后出现糖尿和蛋白尿，并伴有线粒体形态异常。在第七和八周，当肾脏镉浓度达到约200微克/克组织时，病情发展为细胞肿胀，最终坏死。结论是镉诱导的肾病发展有两个阶段。第一阶段是适应期，特征是平滑内质网、微体和次级溶酶体有所增加，肝脏和肾脏细胞内存在金属硫蛋白，但血浆中未检测到金属硫蛋白，尿镉也未增加。第二阶段是毒性期，特征是血浆中可检测到低分子量镉结合物质以及肾小管功能障碍的证据，随后肾小管内衬细胞出现致命损伤。
