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Titanium dioxide nanoparticles (TiO2-NPs) have found wide applications in medical and industrial fields. However, the toxic effect of various tissues is still under study. In this study, we evaluated the toxic effect of TiO2-NP on stomach, liver, and kidney tissues and the amelioration effect of clove oil nanoemulsion (CLV-NE) against DNA damage, oxidative stress, pathological changes, and the apoptotic effect of TiO2-NPs. Four groups of male mice were subjected to oral treatment for five consecutive days including, the control group, the group treated with TiO2-NPs (50 mg/kg), the group treated with (CLV-NE) (5% of the MTD), and the group treated with TiO2-NPs plus CLV-NE. The results revealed that the treatment with TiO2-NPs significantly caused DNA damage in the liver, stomach, and kidney tissues due to increased ROS as indicated by the reduction of the antioxidant activity of SOD and Gpx and increased MDA level. Further, abnormal histological signs and apoptotic effect confirmed by the significant elevation of p53 expression were reported after TiO2-NPs administration. The present data reported a significant improvement in the previous parameters after treatment with CLV-NE. These results showed the collaborative effect of the oils and the extra role of nanoemulsion in enhancing antioxidant effectiveness that enhances its disperse-ability and further promotes its controlled release. One could conclude that CLV-NE is safe and can be used as a powerful antioxidative agent to assess the toxic effects of the acute use of TiO2-NPs.

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Objective: The current study was designed to investigate the protective effects of curcuma caplet against titanium dioxide nanoparticles (nTiO2)-induced damage in liver and kidney of male Wistar rats. Materials and Methods: Thirty adult (7-8 week old) male rats (200 g) were randomly divided into 5 groups of 6 each. The first and second groups received olive oil and nTiO2 (300 mg/kg body weight) as control and nTiO2 groups, respectively. The third, fourth, and fifth groups received Curcuma at concentrations of 100, 200, and 300 mg/kg body weight in addition to 300 mg/kg body weight of nTiO2, respectively. The treatment was performed through gavage for 3 weeks. Rats' blood was examined for total antioxidant capacity (TAC), total oxidant status (TOS), and malondialdehyde (MDA) levels as well as antioxidant enzymes superoxide dismutase (SOD), and glutathione peroxidase (GPx), and activity of liver enzymes alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and renal factors (urea, uric acid, and creatinine). Histological analyses were also performed to estimate the extent of hepatic and renal injury. Results: nTiO2-induced liver and kidney damage by decreased serum SOD, GPx, and TAC (p<0.05). Fu +rthermore, nTiO2 increased serum MDA and TOS, and renal (Creatinine, Urea and Uric acid) and liver parameters (ALT, AST, ALP and LDH) (p<0.05). However, Curcuma treatment was able to moderate these changes dramatically (p<0.05). The results were confirmed by histopathological data. Conclusion: This study showed the antioxidant properties of curcuma against the side effects of nTiO2.

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Nanoscale zero-valent iron particles (NZVI) are widely used in a variety of industries owing to their advantageous mechanical, physical, and chemical properties. These particles can be released into environmental media, including water, soil, and air, through several pathways. NZVI in the ecosystem can be taken up, excreted and distributed within organisms, which is harmful to plants, animals and humans. Plants play a significant role as producers in the ecological circle and can both positively and negatively affect the ecological behavior of NZVI. Therefore, understanding the relationship between plants and NZVI is likely to be of great value for the assessment of NZVI-associated risks and future research directions. In this review, we summarize the current knowledge on the uptake, distribution, and accumulation of NZVI in plants; the phytotoxicity triggered by NZVI exposure at the physiological, biochemical, and molecular levels; and the defense mechanism used by plants to defend against NZVI-induced insults. We further discuss the toxic effects of NZVI on soil animals and microorganisms as well as the risk posed by the presence of NZVI in the food chain.

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BACKGROUND: Antibiotic resistance is one of the current threats to human health, forcing the use of drugs that are more noxious, costlier, and with low efficiency. There are several causes behind antibiotic resistance, including over-prescription of antibiotics in both humans and livestock. In this scenario, researchers are shifting to new alternatives to fight back this concerning situation. SCOPE AND APPROACH: Nanoparticles have emerged as new tools that can be used to combat deadly bacterial infections directly or indirectly to overcome antibiotic resistance. Although nanoparticles are being used in the pharmaceutical industry, there is a constant concern about their toxicity toward human health because of the involvement of well-known toxic chemicals (i.e., sodium/potassium borohydride) making their use very risky for eukaryotic cells. KEY FINDINGS AND CONCLUSIONS: Multiple nanoparticle-based approaches to counter bacterial infections, providing crucial insight into the design of elements that play critical roles in the creation of antimicrobial nanotherapeutic drugs, are currently underway. In this context, plant-based nanoparticles will be less toxic than many other forms, which constitute promising candidates to avoid widespread damage to the microbiome associated with current practices. This article aims to review the actual knowledge on plant-based nanoparticle products for antibiotic resistance and the possible replacement of antibiotics to treat multidrug-resistant bacterial infections.

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Nanomaterials are now being used in a wide variety of biomedical applications. Medical and health-related issues, however, have raised major concerns, in view of the potential risks of these materials against tissue, cells, and/or organs and these are still poorly understood. These particles are able to interact with the body in countless ways, and they can cause unexpected and hazardous toxicities, especially at cellular levels. Therefore, undertaking in vitro and in vivo experiments is vital to establish their toxicity with natural tissues. In this review, we discuss the underlying mechanisms of nanotoxicity and provide an overview on in vitro characterizations and cytotoxicity assays, as well as in vivo studies that emphasize blood circulation and the in vivo fate of nanomaterials. Our focus is on understanding the role that the physicochemical properties of nanomaterials play in determining their toxicity.

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Metal nanoparticles have been extensively investigated for different types of pharmaceutical applications. However, their use has raised some concerns about their toxicity involving the increase of reactive oxygen species causing cellular apoptosis. Therefore, in this review we summarize the most relevant toxicity mechanisms of gold, silver, copper and copper oxide nanoparticles as well as production methods of metal nanoparticles. Parameters involved in their toxicity such as size, surface charge and concentration are also highlighted. Moreover, a critical revision of the literature about the strategies used to reduce the toxicity of this type of nanoparticles is carried out throughout the review. Additionally, surface modifications using different coating strategies, nanoparticles targeting and morphology modifications are deeply explained.

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Due to many uses of zinc oxide nanoparticles (ZnO NPs) in various industries, the release of these particles in the environment and their effects on living organisms is inevitable. In this study, the role of salicylic acid (SA) pretreatments in modulating the toxicity of ZnO NPs was investigated using a hydroponic system. After pretreatment with different concentrations of SA (0, 25, 75, and 150 µM), Chenopodium murale plants were exposed to ZnO NPs (50 mg L-1). The results showed that exogenous SA increased the length, weight, chlorophyll, proline, starch, and soluble sugars in the plants. Besides, SA pretreatments improved water status in the plants treated with ZnO NPs. In SA-pretreated plants, increased activity of catalase (CAT), guaiacol peroxidase (GPX), and superoxide dismutase (SOD) was associated with a decline in electrolyte leakage (EL %) and membrane peroxidation. Under NPs stress, SA pretreatments increased the content of phenolic compounds by increasing the activity of phenylalanine ammonia-lyase (PAL). Exogenous SA reduced the translocation of larger amounts of Zn to the shoots, with more accumulation in the roots. This result can be used to produce healthy food from plants grown in environments contaminated with nanoparticles. It seems that all concentrations of SA reduced the symptoms of ZnO NPs toxicity in the plant by strengthening the function of the antioxidant system and increasing the content of some metabolites. Findings also suggest that SA pretreatment can compensate for the growth reduction caused by ZnO NPs.

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Nickel nanoparticles (Ni-NPs) have advantageous applications in the industry; however, little is known of their adverse effects on biological tissues. In the present study, the ground beetle Blaps polycresta was employed as a sensitive indicator for nickel oxide nanoparticles (NiO-NPs) toxicity. Adult male beetles were injected with six dose levels of NiO-NPs (0.01, 0.02, 0.03, 0.04, 0.05, and 0.06 mg/g body weight). Mortality was reported daily over 30 days under laboratory conditions to establish an LD50. Nickel was detected in the testicular tissues of the beetles using X-ray analysis and transmission electronic microscopy. Beetles treated with the sublethal dose of 0.02 mg/g were selected to observe molecular, cellular, and subcellular changes. Gene transcripts of HSP70, HSP90, and MT1 were found to be increased >2.5-, 1.5-, and 2-fold, respectively, in the treated group compared with the controls. Decreased gene expression of AcPC01, AcPC02, and AcPC04 (≤1.5-, ≤2-, and < 2.5-fold, respectively, vs. controls) also were reported in the treated group. Under light microscopy, various structural changes were observed in the testicular tissues of the treated beetles. Ultrastructure observations using scanning and transmission electron microscopy showed severe damage to the subcellular organelles as well as deformities of the heads and flagella of the spermatozoa. Therefore, the present study postulated the impact of NiO-NPs in an ecological model.

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Biocompatible lipid polymer nanoparticles (NPs) previously used as antimicrobial agents are explored here as immuno-adjuvants. Poly (methyl methacrylate) (PMMA)/dioctadecyldimethylammonium bromide (DODAB)/poly (diallyldimethylammonium chloride) (PDDA) nanoparticles (NPs) were prepared by emulsion polymerization of methyl methacrylate (MMA) in the presence of DODAB and PDDA, with azobisisobutyronitrile (AIBN) as the initiator. NPs characterization after dialysis by dynamic light-scattering yielded 225 ± 2 nm hydrodynamic diameter (Dz), 73 ± 1 mV zeta-potential (ζ), and 0.10 ± 0.01 polydispersity (P). Ovalbumin (OVA) adsorption reduced ζ to 45 ± 2 mV. Balb/c mice immunized with NPs/OVA produced enhanced OVA-specific IgG1 and IgG2a, exhibited moderate delayed type hypersensitivity reaction, and enhanced cytokines production (IL-4, IL-10, IL-2, IFN-γ) by cultured spleen cells. There was no cytotoxicity against cultured macrophages and fibroblasts. Advantages of the PMMA/DODAB/PDDA NPs were high biocompatibility, zeta-potential, colloidal stability, and antigen adsorption. Both humoral and cellular antigen-specific immune responses were obtained.

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Biocompatible lipid polymer nanoparticles (NPs) previously used as antimicrobial agents are explored here as immuno-adjuvants. Poly (methyl methacrylate) (PMMA)/dioctadecyldimethylammonium bromide (DODAB)/poly (diallyldimethylammonium chloride) (PDDA) nanoparticles (NPs) were prepared by emulsion polymerization of methyl methacrylate (MMA) in the presence of DODAB and PDDA, with azobisisobutyronitrile (AIBN) as the initiator. NPs characterization after dialysis by dynamic light-scattering yielded 225 ± 2 nm hydrodynamic diameter (Dz), 73 ± 1 mV zeta-potential (ζ), and 0.10 ± 0.01 polydispersity (P). Ovalbumin (OVA) adsorption reduced ζ to 45 ± 2 mV. Balb/c mice immunized with NPs/OVA produced enhanced OVA-specific IgG1 and IgG2a, exhibited moderate delayed type hypersensitivity reaction, and enhanced cytokines production (IL-4, IL-10, IL-2, IFN-γ) by cultured spleen cells. There was no cytotoxicity against cultured macrophages and fibroblasts. Advantages of the PMMA/DODAB/PDDA NPs were high biocompatibility, zeta-potential, colloidal stability, and antigen adsorption. Both humoral and cellular antigen-specific immune responses were obtained.

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This review presents a perspective on the research trends and solutions from recent years in the domain of antimicrobial packaging materials. The antibacterial, antifungal, and antioxidant activities can be induced by the main polymer used for packaging or by addition of various components from natural agents (bacteriocins, essential oils, natural extracts, etc.) to synthetic agents, both organic and inorganic (Ag, ZnO, TiO2 nanoparticles, synthetic antibiotics etc.). The general trend for the packaging evolution is from the inert and polluting plastic waste to the antimicrobial active, biodegradable or edible, biopolymer film packaging. Like in many domains this transition is an evolution rather than a revolution, and changes are coming in small steps. Changing the public perception and industry focus on the antimicrobial packaging solutions will enhance the shelf life and provide healthier food, thus diminishing the waste of agricultural resources, but will also reduce the plastic pollution generated by humankind as most new polymers used for packaging are from renewable sources and are biodegradable. Polysaccharides (like chitosan, cellulose and derivatives, starch etc.), lipids and proteins (from vegetal or animal origin), and some other specific biopolymers (like polylactic acid or polyvinyl alcohol) have been used as single component or in blends to obtain antimicrobial packaging materials. Where the package's antimicrobial and antioxidant activities need a larger spectrum or a boost, certain active substances are embedded, encapsulated, coated, grafted into or onto the polymeric film. This review tries to cover the latest updates on the antimicrobial packaging, edible or not, using as support traditional and new polymers, with emphasis on natural compounds.

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In line with the 3R concept, nanotoxicology is shifting from a phenomenological to a mechanistic approach based on in vitro and in silico methods, with a consequent reduction in animal testing. Risk Assessment (RA) and Life Cycle Assessment (LCA) methodologies, which traditionally rely on in vivo toxicity studies, will not be able to keep up with the pace of development of new nanomaterials unless they adapt to use this new type of data. While tools and models are already available and show a great potential for future use in RA and LCA, currently none is able alone to quantitatively assess human hazards (i.e. calculate chronic NOAEL or ED50 values). By highlighting which models and approaches can be used in a quantitative way with the available knowledge and data, we propose an integrated pathway for the use of in vitro data in RA and LCA. Starting with the characterization of nanoparticles' properties, the pathway then investigates how to select relevant in vitro human data, and how to bridge in vitro dose-response relationships to in vivo effects. If verified, this approach would allow RA and LCA to stir up the development of nanotoxicology by giving indications about the data and quality requirements needed in risk methodologies.

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Nanoparticle(NP)-based materials have breakthrough applications in many fields of life, such as in engineering, communications and textiles industries; food and bioenvironmental applications; medicines and cosmetics, etc. Biomedical applications of NPs are very active areas of research with successful translation to pharmaceutical and clinical uses overcoming both pharmaceutical and clinical challenges. Although the attractiveness and enhanced applications of these NPs stem from their exceptional properties at the nanoscale size, i.e. 1-1000 nm, they exhibit completely different physicochemical profiles and, subsequently, toxicological profiles from their parent bulk materials. Hence, the clinical evaluation and toxicological assessment of NPs interactions within biological systems are continuously evolving to ensure their safety at the nanoscale. The pulmonary system is one of the primary routes of exposure to airborne NPs either intentionally, via aerosolized nanomedicines targeting pulmonary pathologies such as cancer or asthma, or unintentionally, via natural NPs and anthropogenic (man-made) NPs. This review presents the state-of-the-art, contemporary challenges, and knowledge gaps in the toxicological assessment of NPs interactions with the pulmonary system. It highlights the main mechanisms of NP toxicity, factors influencing their toxicity, the different toxicological assessment methods and their drawbacks, and the recent NP regulatory guidelines based on literature collected from the research pool of NPs interactions with lung cell lines, in vivo inhalation studies, and clinical trials.

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Silica Nanoparticles (SiNPs) is widely used in many fields including antibacterial agent, molecular probe and drug delivery forits special physicochemical properties. Recently, the biosecurity of nano-materials has become a hot spot of research in toxicology due to special structure and functional activeness of nano-materials. This paper briefly summarized recent researchreports at home and abroadto review the toxicity of SiNPs on cells and animals, the factors for influencing the toxicity of SiNPs and the mechanisms underlying SiNPs biotoxicity, aiming to provide references for the development, application and biosecurity of SiNPs.

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The release of nanoparticles and biodegradable chelating agents into the environment may cause toxicological and ecotoxicological effects. The aim of this study is to determine the ecotoxic effects of zinc oxide (ZnO) nanoparticles and ethylenediamine disuccinic acid (EDDS) on most cultured four plants. The durum wheat, bread wheat, barley, and rye are exposed to 5 mL 10 mg L-1 ZnO nanoparticles and 10 mg L-1 EDDS in the seed germination stage. Results show that these different plant species have different responses to ZnO nanoparticles and EDDS. The germination percentage of bread wheat and rye decreases in the application of ZnO nanoparticles while the germination of durum wheat and barley increases as much as in radicle elongation and seedling vigor. While ZnO treatment causes a decrease in bread wheat and rye germinated rat in the range of 33-14.3%, respectively, there is no change in germination rate of these plants at EDDS treatment. In addition, EDDS treatment positively affects barley germination rate. In conclusion, it is clear that ZnO nanoparticles have more toxic effects on bread wheat and rye than EDDS, while barley is positively affected by ZnO nanoparticles and EDDS.

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The current study evaluated the hazards of Zinc oxide nanoparticles (ZnONPs) on Nile Tilapia liver and gill antioxidants enzymes activities and antioxidants genes expressions. The ameliorative action of vitamins E and C mixture was investigated. Two hundred males of Nile Tilapia were exposed to one and two mg L-1 of ZnONPs either with or without vitamin C and E mixture for 7 and 15 days. Glutathione reductase (GR), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) activities and gene expression as well glutathione (GSH) and lipid peroxide (LPO) levels were investigated. The results revealed that the exposure to ZnONPs could induce alterations in the liver and gills antioxidants and LPO of Nile Tilapia. Moreover, the mixture of vitamin E and C highly effective in alleviation the toxic effect of ZnONPs.

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Nanoparticles (NP) bioactivity is under deep scrutiny. In this work, the antioxidant response to TiO2-NP in wheat (Triticum aestivum) was determined. For that, enzymatic and the non-enzymatic antioxidants were evaluated in plants exposed to the P25 anatase:rutile material composed of TiO2-NP and under environmentally realistic doses (0; 5; 50; 150 mg/L for 20 days). Shoot but not root growth was reduced. In leaves, thiol metabolism and ascorbate accumulation were the preferred route whereas in roots the pre-existing antioxidant capacity was preferentially utilized. Both leaves and roots showed increased glutathione reductase and dehydroascorbate reductase activities and decreased ascorbate peroxidase activity. Roots, nevertheless, presented higher enzymatic basal levels than leaves. On the other hand, when examining non-enzymatic antioxidants, the ratio of reduced-to-oxidized glutathione (GSH/GSSG) increased in leaves and decreased in roots. Exposed leaves also presented higher total ascorbate accumulation compared to roots. TiO2-NP exposure down regulated, with more prominence in roots, antioxidant enzyme genes encoding catalase, ascorbate peroxidase, monodehydroascorbate reductase and dehydroascorbate reductase. In leaves, superoxide dismutase gene expression was increased. All data pinpoint to TiO2-NP toxicity above 5 mg/L, with aerial parts being more susceptible, which draws concerns on the safety doses for the use of these NPs in agricultural practices.

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Gold nanoparticles of comparable size were synthetized using honey mediated green method (AuNPs@honey) and citrate mediated Turkevich method (AuNPs@citrate). Their colloidal behavior in two cell media DMEM and RPMI, both supplemented with 10% FBS, was systematically investigated with different characterization techniques in order to evidence how the composition of the media influences their stability and the development of protein/NP complex. We revealed the formation of the protein corona which individually covers the nanoparticles in RPMI media, like a dielectric spacer according to UV-Vis spectroscopy, while DMEM promotes more abundant agglomerations, clustering together the nanoparticles, according to TEM investigations. In order to evaluate the biological impact of nanoparticles, B16 melanoma and L929 mouse fibroblasts cells were used to carry out the viability assays. Generally, the L929 cells were more sensitive than B16 cells to the presence of gold nanoparticles. Measurements of cell viability, proliferation and apoptotic activities of B16 cells indicated that the effects induced by AuNPs@honey were slightly similar to those induced by AuNPs@citrate, however, the toxic response improved in the L929 fibroblast cells following the treatment with AuNPs@honey within the same concentration range from 1 µg/ml to 15 µg/ml for 48 h. Results showed that honey mediated synthesis generates nanoparticles with reduced toxicity trends depending on the cell type, concentration of nanoparticles and exposure time toward various biomedical applications.

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Silver nanoparticles are currently one of the most widely used metallic nanoparticles. Due to their antibacterial properties, they are applied in textiles, house-holds items, and medical devices, among many other products. Understanding the potential toxicity associated with silver nanoparticles and the differential effect that nanoparticles of different size might induce is crucial, due to the increasing human and environmental exposure to this type of nanoparticles. In this work, we explored the different biomolecular mechanisms underlying the toxicity of silver nanoparticles in a size-dependent manner. Quantitative proteomic analysis of hepatic cells exposed to 10 and 60 nm silver nanoparticles demonstrated the alteration of a different set of proteins depending on the particle size. We demonstrated that while 10 nm silver nanoparticles induce nucleolar stress and ribosome biogenesis halt, both types of nanoparticles induce DNA damage and oxidative stress but through different pathways. In addition, both types of nanoparticles also affected cell proliferation, disrupted the cell cycle and ultimately, induced apoptosis. The alteration of different cellular mechanisms in a size-dependent manner, have relevant implications not only from a toxicity point of view, but also for the potential applications of silver nanoparticles.

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From that time AgNPs become one of the most accessible and important antibacterial agents in our world, thousands of papers published regarding investigating all aspects of these materials. When the time elapsed and novel methods contrived to follow the fingerprint of AgNPs in the in vivo models, some critical concerns and arguments also appeared between researchers about the safety of these compounds for living cells and vital organs. The paper by Dehvari and Ghahaghaei published in Volume 108 International Journal of Biological Macromolecules, pages 1128-1139 (Dehvari and Ghahghaei, 2018) suffered some errors from safety concerns to obscurities in the results essentially needing the amendment to enhance its quality. Though the author(s) idea is commended enough, nevertheless, I could not find a profound trace with their results, and my concerns are discussed in detail as the following lines.

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