Kadammattil Ambika Vishnu, Sajankila Shyama Prasad, Prabhu Suma, Rao Bhuvanagiri Nageshwar, Rao Bola Sadashiva Satish
Department of Biotechnology, School of Life Sciences, Manipal University, Manipal 576104, Karnataka, India.
Department of Biotechnology, NMAM Institute of Technology, NITTE Educational Trust, Karkala Taluk, Udupi 574110, Karnataka, India.
J Nanosci Nanotechnol. 2018 Apr 1;18(4):2394-2404. doi: 10.1166/jnn.2018.14542.
Acceleration in development of metallic nanoparticles for their utility in medical and technological applications due to their unique physicochemical properties has concurrently raised a matter of concern due to their potential toxicity. Of the enormous metallic nanostructures, copper oxide nanoparticles (CuONPs) having optical and electrochemical properties are scrutinized for theranostic applications. Therefore, their safety profile is of a major concern in optimizing a safe dose for its clinical utility. Considering the potency of CuONPs in epitomizing toxicity, we report a dose and time dependent acute, systemic and transgenerational toxicity profile of CuONPs in comparison to the bulk copper as copper sulfate (CuSO4). Acute toxic dose (LD50(14)) of CuONPs (400 mg/kg · b · wt) was found to be three fold higher that of CuSO4(100 mg/kg · b · wt). Comparative steady state evaluation showed that CuONPs (≥5 mg/kg · b · wt.) induce greater dose and time dependent oxidative stress by increase in protein carbonylation and decreased glutathione levels in comparison to the bulk CuSO4. Furthermore, CuONPs were found to disrupt blood brain barrier (BBB) and sneak in to the brain which was quantified by atomic absorption spectroscopy (AAS) and also coax toxicity in liver, kidney and spleen, ascertained by histopathological findings (at ≥5 mg/kg · b · wt.). Considering transgenerational toxicity, CuONPs in comparison to CuSO4 severely affected sperm count and morphology in male animals, though not much teratological effects were observed, except certain extent of embryo resorption. The present study highlights a complete toxicity profile of CuONPs, giving forethought for considering them for clinical applications.
由于金属纳米颗粒独特的物理化学性质，其在医学和技术应用中的发展加速，与此同时，因其潜在毒性也引发了人们的关注。在众多金属纳米结构中，具有光学和电化学性质的氧化铜纳米颗粒（CuONPs）被用于诊疗应用研究。因此，其安全性在优化临床应用安全剂量方面是一个主要关注点。考虑到CuONPs具有典型毒性，我们报告了与作为硫酸铜（CuSO4）的块状铜相比，CuONPs的剂量和时间依赖性急性、全身和跨代毒性特征。发现CuONPs的急性毒性剂量（LD50(14)）（400毫克/千克·体重）是CuSO4（100毫克/千克·体重）的三倍。比较稳态评估表明，与块状CuSO4相比，CuONPs（≥5毫克/千克·体重）通过增加蛋白质羰基化和降低谷胱甘肽水平诱导更大的剂量和时间依赖性氧化应激。此外，发现CuONPs会破坏血脑屏障（BBB）并进入大脑，这通过原子吸收光谱法（AAS）进行定量，并且还会在肝脏、肾脏和脾脏中引发毒性，这通过组织病理学检查结果（≥5毫克/千克·体重）得以确定。考虑到跨代毒性，与CuSO4相比，CuONPs严重影响雄性动物的精子数量和形态，尽管除了一定程度的胚胎吸收外，未观察到太多致畸作用。本研究突出了CuONPs的完整毒性特征，为其临床应用的考虑提供了预先思考。
