Hayashi T, Sudo J
Department of Toxicology and Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Higashi-Nippon-Gakuen University, Hokkaido, Japan.
J Toxicol Sci. 1994 Feb;19(1):45-53. doi: 10.2131/jts.19.45.
An interrelation of Cd-contents with hepato- and nephrotoxicities, and a mechanism for Cd-exclusion from kidneys were investigated in rats that received a single intravenous injection of either CdCl2 or Cd-saturated metallothionein II (Cd-MT-II) with doses of 0.1 and 0.3 mg Cd/kg body weight (b.w.). Between the livers and kidneys, higher uptake of Cd was observed in the liver in terms of CdCl2, and in the kidney in terms of Cd-MT-II. The CdCl2 at the two doses hardly showed any histopathological alterations in the livers and kidneys. The 0.1 mg Cd/kg b.w. of Cd-MT-II showed a slight injury in the kidneys, while hardly in the livers. At Day 1 of the 0.3 mg Cd/kg b.w. of Cd-MT-II, the renal Cd-contents reached the maximal value of 8.22 +/- 0.36 microgram/g wet tissue, and degeneration including necrosis and defluxion of proximal tubular cells were most highly observed. At Day 5 of the 0.3 mg Cd/kg b.w., the renal Cd-contents were lowered to 2.40 +/- 0.24 micrograms/g wet tissue, and fibrosis and regeneration of the proximal tubular cells were remarkably found. These findings strongly suggested that, in the case of administration of Cd-MT-II, the Cd taken into the kidneys was eliminated from there mainly by cellular death of the proximal tubulus and by their resultant defluxion.
研究了氯化镉(CdCl₂)或镉饱和金属硫蛋白II(Cd-MT-II)单次静脉注射(剂量为0.1和0.3 mg Cd/kg体重)的大鼠中镉含量与肝毒性和肾毒性的相互关系以及肾脏排镉机制。在肝脏和肾脏之间,就CdCl₂而言,肝脏中镉的摄取量较高;就Cd-MT-II而言,肾脏中镉的摄取量较高。两种剂量的CdCl₂在肝脏和肾脏中几乎未显示任何组织病理学改变。0.1 mg Cd/kg体重的Cd-MT-II在肾脏中显示出轻微损伤,而在肝脏中几乎没有。在0.3 mg Cd/kg体重的Cd-MT-II处理第1天,肾脏镉含量达到最大值8.22±0.36微克/克湿组织,近端肾小管细胞的变性包括坏死和脱落最为明显。在0.3 mg Cd/kg体重处理第5天,肾脏镉含量降至2.40±0.24微克/克湿组织,近端肾小管细胞的纤维化和再生明显。这些发现有力地表明,在给予Cd-MT-II的情况下,进入肾脏的镉主要通过近端小管的细胞死亡及其导致的脱落而从肾脏中排出。