Hong Jeong-Sup, Park Myeong-Kyu, Kim Min-Seok, Lim Jeong-Hyeon, Park Gil-Jong, Maeng Eun-Ho, Shin Jae-Ho, Kim Yu-Ri, Kim Meyoung-Kon, Lee Jong-Kwon, Park Jin-A, Kim Jong-Choon, Shin Ho-Chul
Health Care Research Laboratory, Korea Testing and Research Institute, Gimpo, Korea ; College of Veterinary Medicine, Konkuk University, Seoul, Korea.
Health Care Research Laboratory, Korea Testing and Research Institute, Gimpo, Korea.
Int J Nanomedicine. 2014 Dec 15;9 Suppl 2(Suppl 2):145-57. doi: 10.2147/IJN.S57931. eCollection 2014.
This study investigated the potential adverse effects of zinc oxide nanoparticles (ZnO(SM20[-]) NPs; negatively charged, 20 nm) on pregnant dams and embryo-fetal development after maternal exposure over the period of gestational days 5-19 with Sprague Dawley rats. ZnO(SM20(-)) NPs were administered to pregnant rats by gavage at 0 mg/kg/day, 100 mg/kg/day, 200 mg/kg/day, and 400 mg/kg/day. All dams were subjected to caesarean section on gestational day 20, and all the fetuses were examined for external, visceral, and skeletal alterations. Toxicity in the dams manifested as significantly decreased body weight at 400 mg/kg/day and decreased liver weight, and increased adrenal glands weight at 200 mg/kg/day and 400 mg/kg/day. However, no treatment-related difference in the number of corpora lutea, the number of implantation sites, the implantation rate (%), resorption, dead fetuses, litter size, fetal deaths, fetal and placental weights, and sex ratio were observed between the groups. Morphological examinations of the fetuses demonstrated no significant difference in the incidences of abnormalities between the groups. No significant difference was found in the Zn content of fetal tissue between the control and high-dose groups. These results showed that a 15-day repeated oral dose of ZnO(SM20(-)) was minimally maternotoxic at dose of 200 mg/kg/day and 400 mg/kg/day.
本研究调查了氧化锌纳米颗粒(ZnO(SM20[-]) NPs;带负电荷,直径20 nm)在妊娠第5至19天经口暴露于斯普拉格-道利大鼠母体后,对孕鼠及胚胎-胎儿发育的潜在不良影响。将ZnO(SM20(-)) NPs以0 mg/kg/天、100 mg/kg/天、200 mg/kg/天和400 mg/kg/天的剂量经口灌胃给予孕鼠。所有孕鼠于妊娠第20天进行剖腹产,并对所有胎儿进行外观、内脏和骨骼改变检查。母鼠的毒性表现为在400 mg/kg/天时体重显著下降,在200 mg/kg/天和400 mg/kg/天时肝脏重量下降,肾上腺重量增加。然而,各组间在黄体数量、着床部位数量、着床率(%)、吸收、死胎、窝仔数、胎儿死亡、胎儿及胎盘重量和性别比例方面未观察到与治疗相关的差异。对胎儿的形态学检查表明,各组间畸形发生率无显著差异。对照组和高剂量组胎儿组织中的锌含量无显著差异。这些结果表明,15天重复经口给予ZnO(SM20(-)),在200 mg/kg/天和400 mg/kg/天的剂量下对母体的毒性最小。