Scharf Brian, Trombetta Louis David
Department of Biological Sciences, St. John's University, Queens, New York, USA.
J Toxicol Environ Health A. 2008;71(19):1300-6. doi: 10.1080/15287390802240744.
This study examined the toxicity and accumulation of copper in the livers and kidneys of Long-Evans rats after a subacute exposure to copper dimethyldithiocarbamate (CDCC) wood preservative. CDDC was recently introduced as an alternative to chromated copper arsenate (CCA) preserved wood. Female rats (220-270 g) were treated with 0, 25, 50, or 75 mg/kg CDDC by oral gavage for 3 wk. Light microscopy revealed that higher doses of CDDC induced diffuse necrosis and a loss of sinusoids in the livers of Long-Evans rats with vacuolization in the highest dose. Rats treated with 25 mg/kg CDDC displayed a thickening of the basement membrane of Bowman's capsule and the mesangium. Exposure to higher CDDC concentrations (50 and 75 mg/kg) showed moderate to marked expansion of the mesangial matrix and glomerular necrosis with an overall loss of glomerular structure seen in the highest dose. The concentration of copper was significantly increased in the tissues of animals exposed to CDDC in a dose-dependent manner. Western blot analysis revealed the induction of the stress protein Hsp70 and the formation of 4-hydroxy-2-nonenal (4HNE) adducts in liver and renal tissues, indicating peroxidative damage. CDDC was shown to be toxic to the livers and kidneys, at all doses used, and this toxicity is related to peroxidative insult.
本研究检测了长 Evans 大鼠亚急性暴露于二甲基二硫代氨基甲酸铜(CDCC)木材防腐剂后,肝脏和肾脏中铜的毒性及蓄积情况。CDDC 是最近作为铬酸铜砷酸盐(CCA)防腐木材的替代品引入的。雌性大鼠(220 - 270 克)通过灌胃给予 0、25、50 或 75 毫克/千克 CDDC,持续 3 周。光学显微镜检查显示,较高剂量的 CDDC 可诱导长 Evans 大鼠肝脏出现弥漫性坏死和肝血窦丧失,最高剂量组出现空泡化。用 25 毫克/千克 CDDC 处理的大鼠显示鲍曼囊和系膜的基底膜增厚。暴露于较高 CDDC 浓度(50 和 75 毫克/千克)时,系膜基质出现中度至明显扩张,肾小球坏死,最高剂量组可见肾小球结构整体丧失。暴露于 CDDC 的动物组织中铜浓度呈剂量依赖性显著增加。蛋白质免疫印迹分析显示,应激蛋白 Hsp70 被诱导,肝脏和肾脏组织中形成 4 - 羟基 - 2 - 壬烯醛(4HNE)加合物,表明存在过氧化损伤。结果表明,所用的所有剂量的 CDDC 对肝脏和肾脏均有毒性,且这种毒性与过氧化损伤有关。