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      International Journal of Nanomedicine (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the application of nanotechnology in diagnostics, therapeutics, and drug delivery systems throughout the biomedical field. Sign up for email alerts here.

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      Comparative Toxicological Effects of Biologically and Chemically Synthesized Copper Oxide Nanoparticles on Mice

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          Abstract

          Introduction

          Copper oxide nanoparticles (CuO-NPs) are widely used as feed additives for livestock and poultry and implicated in many biomedical applications; however, overload of copper NPs induces various toxicological changes and dysfunction of animal’s organs. Thus, this study was designed to evaluate the comparative toxicological effects of biologically and chemically synthesized CuO-NPs on mice.

          Methods

          Transmission electron microscopy (TEM), X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FT-IR) were used to characterize the sizes, shapes and functional groups of CuO-NPs. Forty-five mice were randomly allocated into three groups. Control group received distilled water. The second group was administered a single dose of biologically synthesized CuO-NPs (500 mg/kg bw) orally. The third group was administered a single dose of chemically synthesized CuO-NPs (500 mg/kg bw) orally.

          Results

          TEM revealed that biologically synthesized NPs were spherical in shape, whereas chemically synthesized NPs were spherical or elongated in shape. XRD showed that the size of biologically synthesized NPs ranged from 4.14 to 12.82 nm and that of chemically synthesized NPs ranged from 4.06 to 26.82 nm. FT-IR spectroscopy indicated that the peaks appeared between 779 cm −1 and 425 cm −1 in biologically synthesized NPs and between 858 cm −1 and 524 cm −1 in chemically synthesized NPs were for Cu-O nanostructure. Four mice died due to administration of biologically synthesized CuO-NPs. Both biologically and chemically synthesized CuO-NPs induced leukocytosis, elevated serum activities of alanine aminotransferase and aspartate aminotransferase and serum levels of urea and creatinine and increased P53 mRNA and caspase-3 protein expressions in hepatic tissues. Moreover, CuO-NPs induced degenerative and necrotized changes in hepatic, renal and splenic tissues. Biochemical, apoptotic and pathological changes were more serious in mice administered with biologically synthesized CuO-NPs.

          Conclusion

          This study indicated that a high dose of biologically and chemically synthesized CuO-NPs induced adverse effects on hepatic, renal and splenic tissues. At the same dose level, the biologically synthesized CuO-NPs evoked more potent toxic effects than the chemically synthesized CuO-NPs.

          Most cited references54

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          Safety assessment for nanotechnology and nanomedicine: concepts of nanotoxicology.

          Nanotechnology, nanomedicine and nanotoxicology are complementary disciplines aimed at the betterment of human life. However, concerns have been expressed about risks posed by engineered nanomaterials (ENMs), their potential to cause undesirable effects, contaminate the environment and adversely affect susceptible parts of the population. Information about toxicity and biokinetics of nano-enabled products combined with the knowledge of unintentional human and environmental exposure or intentional delivery for medicinal purposes will be necessary to determine real or perceived risks of nanomaterials. Yet, results of toxicological studies using only extraordinarily high experimental doses have to be interpreted with caution. Key concepts of nanotoxicology are addressed, including significance of dose, dose rate, and biokinetics, which are exemplified by specific findings of ENM toxicity, and by discussing the importance of detailed physico-chemical characterization of nanoparticles, specifically surface properties. Thorough evaluation of desirable versus adverse effects is required for safe applications of ENMs, and major challenges lie ahead to answer key questions of nanotoxicology. Foremost are assessment of human and environmental exposure, and biokinetics or pharmacokinetics, identification of potential hazards, and biopersistence in cells and subcellular structures to perform meaningful risk assessments. A specific example of multiwalled carbon nanotubes (MWCNT) illustrates the difficulty of extrapolating toxicological results. MWCNT were found to cause asbestos-like effects of the mesothelium following intracavitary injection of high doses in rodents. The important question of whether inhaled MWCNT will translocate to sensitive mesothelial sites has not been answered yet. Even without being able to perform a quantitative risk assessment for ENMs, due to the lack of sufficient data on exposure, biokinetics and organ toxicity, until we know better it should be made mandatory to prevent exposure by appropriate precautionary measures/regulations and practicing best industrial hygiene to avoid future horror scenarios from environmental or occupational exposures. Similarly, safety assessment for medical applications as key contribution of nanotoxicology to nanomedicine relies heavily on nano-specific toxicological concepts and findings and on a multidisciplinary collaborative approach involving material scientists, physicians and toxicologists.
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            Effects of nanomaterial physicochemical properties on in vivo toxicity.

            It is well recognized that physical and chemical properties of materials can alter dramatically at nanoscopic scale, and the growing use of nanotechnologies requires careful assessment of unexpected toxicities and biological interactions. However, most in vivo toxicity concerns focus primarily on pulmonary, oral, and dermal exposures to ultrafine particles. As nanomaterials expand as therapeutics and as diagnostic tools, parenteral administration of engineered nanomaterials should also be recognized as a critical aspect for toxicity consideration. Due to the complex nature of nanomaterials, conflicting studies have led to different views of their safety. Here, the physicochemical properties of four representative nanomaterials (dendrimers, carbon nanotubes, quantum dots, and gold nanoparticles) as it relates to their toxicity after systemic exposure is discussed.
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              Acute toxicological effects of copper nanoparticles in vivo.

              To assess the toxicity of copper nanoparticles (23.5 nm) in vivo, LD(50), morphological changes, pathological examinations and blood biochemical indexes of experimental mice are studied comparatively with micro-copper particles (17 microm) and cupric ions (CuCl(2).2H(2)O). The LD(50) for the nano-, micro-copper particles and cupric ions exposed to mice via oral gavage are 413, >5000 and 110 mg/kg body weight, respectively. The toxicity classes of nano and ionic copper particles both are class 3 (moderately toxic), and micro-copper is class 5 (practically non-toxic) of Hodge and Sterner Scale. Kidney, liver and spleen are found to be target organs of nano-copper particles. Nanoparticles induce gravely toxicological effects and heavy injuries on kidney, liver and spleen of experimental mice, but micro-copper particles do not, on mass basis. Results indicate a gender dependent feature of nanotoxicity. Several factors such as huge specific surface area, ultrahigh reactivity, exceeding consumption of H(+), etc. that likely cause the grave nanotoxicity observed in vivo are discussed.
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                Author and article information

                Journal
                Int J Nanomedicine
                Int J Nanomedicine
                IJN
                intjnano
                International Journal of Nanomedicine
                Dove
                1176-9114
                1178-2013
                28 May 2020
                2020
                : 15
                : 3827-3842
                Affiliations
                [1 ]Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, University of Sadat City , Sadat City, Egypt
                [2 ]Department of Biology, Faculty of Sciences and Arts-Khulais, University of Jeddah , Jeddah, Saudi Arabia
                [3 ]Department of Microbial Biotechnology, Genetic Engineering & Research Institute, University of Sadat City , Sadat City, Egypt
                [4 ]Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, Menoufia University , Sheben Elkom 32511, Egypt
                [5 ]Department of Pathology, Faculty of Veterinary Medicine, University of Sadat City , Sadat City, Egypt
                [6 ]Department of Animal Husbandry and Animal Wealth Development, Faculty of Veterinary Medicine, University of Sadat City , Sadat City, Egypt
                [7 ]Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, University of Sadat City , Sadat City, Egypt
                [8 ]Bioproducts Research Chair, Zoology Department, College of Science, King Saud University , Riyadh, Saudi Arabia
                [9 ]Botany and Microbiology Department, Faculty of Science, Beni-Suef University , Beni-Suef, Egypt
                Author notes
                Correspondence: Mabrouk A Abd Eldaim Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, Menoufia University , Sheben Elkom32511, Egypt Tel/Fax +20482193756; +201117484718 Email mabroukattia@vet.menofia.edu.eg
                Wael N Hozzein Bioproducts Research Chair, Zoology Department, College of Science, King Saud University , Sheben Riyadh, Saudi Arabia Email whozzein@ksu.edu.sa
                Author information
                http://orcid.org/0000-0002-7451-6283
                http://orcid.org/0000-0002-4589-6272
                http://orcid.org/0000-0003-1886-1207
                http://orcid.org/0000-0002-4893-1117
                http://orcid.org/0000-0003-2467-9719
                Article
                241922
                10.2147/IJN.S241922
                7269235
                32581533
                2b302089-2f70-4d75-a76c-bf0092c7286c
                © 2020 El Bialy et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Page count
                Figures: 6, Tables: 4, References: 66, Pages: 16
                Categories
                Original Research

                Molecular medicine
                biologically synthesized cuo-nps,chemically synthesized cuo-nps,p53,caspase
                Molecular medicine
                biologically synthesized cuo-nps, chemically synthesized cuo-nps, p53, caspase

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