Goyer R A, Miller C R, Zhu S Y, Victery W
National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27514.
Toxicol Appl Pharmacol. 1989 Nov;101(2):232-44. doi: 10.1016/0041-008x(89)90272-x.
Male rats were injected SC with 0.6 mg Cd/kg/day for 5 days per week for 2, 4, 6, and 8 weeks. Liver and kidney were examined morphologically and analyzed for metallothionein, cadmium, zinc, and copper. Morphologic changes were found in kidney but not in liver. The earliest ultrastructural change consisted of myelin figures in vacuoles in cytoplasm of proximal tubular lining cells reflecting degeneration of membranes. This change occurred after 4 weeks with 801 +/- 25 nmol/g (89.9 micrograms/g) total kidney cadmium or 390 nmol/g (43.7 micrograms/g) of cadmium not bound to metallothionein. Similar changes were observed after 6 weeks but after 8 weeks pathological changes consisted of focal cellular necrosis and interstitial fibrosis. Other ultrastructural changes included altered mitochondria and increased numbers of microbodies. Renal cadmium after 8 weeks exposure was 1827 +/- 48 nmol/g (215.3 +/- 5.8 micrograms/g) or 628 nmol/g (70.2 micrograms/g) of cadmium not bound to metallothionein. Total cadmium was higher in liver than in kidney but partitioning between bound and nonbound cadmium differed in the two organs. The fraction not bound to metallothionein increased with time of exposure in both liver and kidney. However, total cadmium in the liver did not exceed potentially available binding sites of metallothionein, whereas total cadmium did exceed potentially available binding sites of metallothionein in the kidney where pathologic changes occurred. The results indicated that degeneration of cellular membranes is an early cellular effect of cadmium exposure followed later by toxicity to organelles, cellular necrosis, and interstitial fibrosis. Cadmium-induced cellular toxicity is more directly related to the fraction of cadmium in the kidney that is not bound to metallothionein than is total cadmium per se.
雄性大鼠每周5天皮下注射0.6毫克镉/千克/天，持续2、4、6和8周。对肝脏和肾脏进行形态学检查，并分析金属硫蛋白、镉、锌和铜的含量。在肾脏中发现了形态学变化，而肝脏中未发现。最早的超微结构变化是近端肾小管内衬细胞胞质空泡中的髓鞘样结构，反映了膜的变性。这种变化在4周后出现，此时肾脏总镉含量为801±25纳摩尔/克（89.9微克/克），或未与金属硫蛋白结合的镉含量为390纳摩尔/克（43.7微克/克）。6周后观察到类似变化，但8周后病理变化包括局灶性细胞坏死和间质纤维化。其他超微结构变化包括线粒体改变和微体数量增加。暴露8周后肾脏中的镉含量为1827±48纳摩尔/克（215.3±5.8微克/克），或未与金属硫蛋白结合的镉含量为628纳摩尔/克（70.2微克/克）。肝脏中的总镉含量高于肾脏，但两个器官中结合镉和未结合镉的分布不同。未与金属硫蛋白结合的部分随暴露时间在肝脏和肾脏中均增加。然而，肝脏中的总镉含量未超过金属硫蛋白潜在的可利用结合位点，而在发生病理变化的肾脏中，总镉含量确实超过了金属硫蛋白潜在的可利用结合位点。结果表明，细胞膜变性是镉暴露的早期细胞效应，随后是对细胞器的毒性、细胞坏死和间质纤维化。镉诱导的细胞毒性与肾脏中未与金属硫蛋白结合的镉部分比与总镉本身更直接相关。
