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两种不同给药途径(单次静脉注射和单次口服给药)处理的大鼠中氧化锌纳米颗粒的毒性。

Toxicity of zinc oxide nanoparticles in rats treated by two different routes: single intravenous injection and single oral administration.

作者信息

Choi Jonghye, Kim Heyjin, Kim Pilje, Jo Eunhye, Kim Hyun-Mi, Lee Moo-Yeol, Jin Seon Mi, Park Kwangsik

机构信息

a College of Pharmacy , Dongduk Women's University , Seoul , Korea.

出版信息

J Toxicol Environ Health A. 2015;78(4):226-43. doi: 10.1080/15287394.2014.949949.

Abstract

Toxicokinetics of zinc oxide nanoparticles (ZnONP) was studied in rats via a single intravenous (iv) injection and a single oral administration (3 mg/kg or 30 mg/kg), respectively. Blood concentrations of zinc (Zn) were monitored for 7 d and tissue distribution were determined in liver, kidneys, lung, spleen, thymus, brain, and testes. To ascertain the excretion of ZnONP, Zn levels in urine and feces were measured for 7 d. ZnONP were not readily absorbed from the gastrointestinal tract (GIT) after oral administration and were excreted mostly in feces. When the nanoparticles were injected iv to rats at a dose of 30 mg/kg, peak concentration appeared at 5 min but returned to normal range by d 2 (48 h after injection). ZnONP were distributed mainly to liver, kidneys, lung, and spleen, but not to thymus, brain, and testes. The distribution level was significantly decreased to normal by d 7. Feces excretion levels after iv injection supported biliary excretion of ZnONP. In rats injected iv with 30 mg/kg, mitotic figures in hepatocytes were significantly increased and multifocal acute injuries with dark brown pigment were noted in lungs, while no significant damage was observed in rats treated orally with the same dosage.

摘要

通过单次静脉注射和单次口服给药(3毫克/千克或30毫克/千克),分别在大鼠中研究了氧化锌纳米颗粒(ZnONP)的毒代动力学。监测锌(Zn)的血药浓度7天,并测定肝脏、肾脏、肺、脾脏、胸腺、大脑和睾丸中的组织分布。为确定ZnONP的排泄情况,测量尿液和粪便中的锌水平7天。口服给药后,ZnONP不易从胃肠道(GIT)吸收,主要通过粪便排泄。当以30毫克/千克的剂量静脉注射纳米颗粒给大鼠时,峰值浓度在5分钟出现,但在第2天(注射后48小时)恢复到正常范围。ZnONP主要分布于肝脏、肾脏、肺和脾脏,但未分布于胸腺、大脑和睾丸。到第7天,分布水平显著降至正常。静脉注射后的粪便排泄水平支持ZnONP经胆汁排泄。在以30毫克/千克静脉注射的大鼠中,肝细胞中的有丝分裂象显著增加,肺部出现多灶性急性损伤并伴有深棕色色素沉着,而相同剂量口服给药的大鼠未观察到明显损伤。

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