Kirill S. Golokhvast

Emerging aspects of nanotoxicology in health and disease: From agriculture and food sector to cancer therapeutics.

Nanotechnology is an evolving scientific field that has allowed the manufacturing of materials with novel physicochemical and biological properties, offering a wide spectrum of potential applications. Properties of nanoparticles that contribute to their usefulness include their markedly increased surface area in relation to mass, surface reactivity and insolubility, ability to agglomerate or change size in different media and enhanced endurance over conventional-scale substance. Here, we review nanoparticle classification and their emerging applications in several fields; from active food packaging to drug delivery and cancer research. Nanotechnology has exciting therapeutic applications, including novel drug delivery for the treatment of cancer. Additionally, we discuss that exposure to nanostructures incorporated to polymer composites, may result in potential human health risks. Therefore, the knowledge of processes, including absorption, distribution, metabolism and excretion, as well as careful toxicological assessment is critical in order to determine the effects of nanomaterials in humans and other biological systems. Expanding the knowledge of nanoparticle toxicity will facilitate designing of safer nanocomposites and their application in a beneficial manner.

Cardiotoxicity of nano-particles

Nano-particles (NPs) are used in industrial and biomedical fields such as cosmetics, food additives and biosensors. Beside their favorable properties, nanoparticles are responsible for toxic effects. Local adverse effects and/or systemic toxicity are described with nanoparticle delivery to target organs of the human body. Animal studies provide evidence for the aforementioned toxicity. Cardiac function is a specific target of nanoparticles. Thus, reviewing the current bibliography on cardiotoxicity of nanoparticles and specifically of titanium, zinc, silver, carbon, silica and iron oxide nano-materials is the aim of this study.

Silaffins of Diatoms: From Applied Biotechnology to Biomedicine

Silaffins are involved in the formation of the cell walls of diatoms. It is known that silaffins can precipitate silica in vitro, forming nano- and micro-particles in the shape of spheres and plates containing many pores. It is important to note that the deposition of silica and the particle morphology in the presence of silaffins affects chemical and physical agents (e.g., peptides, polyamines, phosphate, nitrogen, and the mechanical changes of the reaction mixture). It is believed that silaffins act as an organic matrix for silica-genesis and that silica pore size should reflect the pattern of a matrix. Here, biotechnology related to silaffins is discussed in the context of “a hypothesis of silaffin matrix” and “the LCPA-phosphate model”. We discuss the most promising area of silaffin biotechnology—the development of production methods for silicon structures with desired shapes and nanostructural properties that can be used to create biocompatible materials.

Simulating real-life exposures to uncover possible risks to human health: A proposed consensus for a novel methodological approach

In real life, consumers are exposed to complex mixtures of chemicals via food, water and commercial products consumption. Since risk assessment usually focuses on individual compounds, the current regulatory approach doesn’t assess the overall risk of chemicals present in a mixture. This study will evaluate the cumulative toxicity of mixtures of different classes of pesticides and mixtures of different classes of pesticides together with food additives (FAs) and common consumer product chemicals using realistic doses after long-term exposure. Groups of Sprague Dawley (CD-SD) rats (20 males and 20 females) will be treated with mixtures of pesticides or mixtures of pesticides together with FAs and common consumer product chemicals in 0.0, 0.25 × acceptable daily intake (ADI)/tolerable daily intake (TDI), ADI/TDI and 5 × ADI/TDI doses for 104 weeks. All animals will be examined every day for signs of morbidity and mortality. Clinical chemistry hematological parameters, serum hormone levels, biomarkers of oxidative stress, cardiotoxicity, genotoxicity, urinalysis and echocardiographic tests will be assessed periodically at 6 month intervals. At 3-month intervals, ophthalmological examination, test for sensory reactivity to different types of stimuli, together with assessment of learning abilities and memory performance of the adult and ageing animals will be conducted. After 24 months, animals will be necropsied, and internal organs will be histopathologically examined. If the hypothesis of an increased risk or a new hazard not currently identified from cumulative exposure to multiple chemicals was observed, this will provide further information to public authorities and research communities supporting the need of replacing current single-compound risk assessment by a more robust cumulative risk assessment paradigm.

Mechanistic understanding of nanoparticles’ interactions with extracellular matrix: the cell and immune system

Extracellular matrix (ECM) is an extraordinarily complex and unique meshwork composed of structural proteins and glycosaminoglycans. The ECM provides essential physical scaffolding for the cellular constituents, as well as contributes to crucial biochemical signaling. Importantly, ECM is an indispensable part of all biological barriers and substantially modulates the interchange of the nanotechnology products through these barriers. The interactions of the ECM with nanoparticles (NPs) depend on the morphological characteristics of intercellular matrix and on the physical characteristics of the NPs and may be either deleterious or beneficial. Importantly, an altered expression of ECM molecules ultimately affects all biological processes including inflammation. This review critically discusses the specific behavior of NPs that are within the ECM domain, and passing through the biological barriers. Furthermore, regenerative and toxicological aspects of nanomaterials are debated in terms of the immune cells-NPs interactions.

Low-dose occupational exposure to benzene and signal transduction pathways involved in the regulation of cellular response to oxidative stress.

AIMS Benzene metabolism seems to modulate NF-κB, p38-MAPK (mitogen-activated protein kinase) and signal transducer and activator of transcription 3 (STAT3) signalling pathways via the production of reactive oxygen species. This study aims to evaluate the effects of low-dose, long-term exposure on NF-κB, STAT3, p38-MAPK and stress-activated protein kinase/Jun amino-terminal kinase (SAPK/JNK) signal transduction pathways in peripheral blood mononuclear cells in gasoline station attendants. The influence of consumption of vegetables and fruits on these pathways has also been evaluated. MAIN METHODS A total of 91 men, employed in gasoline stations located in eastern Sicily, were enrolled for this study and compared with a control group of 63 male office workers with no history of exposure to benzene. The exposure was assessed by measuring urinary trans,trans-muconic acid (t,t-MA) concentration. Quantitative analyses were performed for proteins NF-κB p65, phospho-NF-κB p65, phospho-IκB-α, phospho-SAPK/JNK, phospho-p38 MAPK and phospho-STAT3 using an immunoenzymatic assay. KEY FINDINGS The results of this study indicate significantly higher t,t-MA levels in gasoline station attendants. With regard to NF-κB, phospho-IκB-α and phospho-STAT3 proteins, statistically significant differences were observed in workers exposed to benzene. However, no differences were observed in SAPK/JNK and p38-MAPK activation. These changes were positively correlated with t,t-MA levels, but only phospho-NF-κB p65 was associated with the intake of food rich in antioxidant active principles. SIGNIFICANCE Chronic exposure to low-dose benzene can modulate signal transduction pathways activated by oxidative stress and involved in cell proliferation and apoptosis. This could represent a possible mechanism of carcinogenic action of chronic benzene exposure.

Effect of surfactant in mitigating cadmium oxide nanoparticle toxicity: Implications for mitigating cadmium toxicity in environment

Abstract Cadmium (Cd), classified as human carcinogen, is an extremely toxic heavy metal pollutant, and there is an increasing environmental concern for cadmium exposure through anthropogenic sources including cigarette smoke. Though Cd based nanoparticles such as cadmium oxide (CdO) are being widely used in a variety of clinical and industrial applications, the toxicity of CdO nanoparticles has not been well characterized. Herein we report the toxicity of CdO nanoparticles employing zebrafish as a model. Two different CdO nanoparticles were prepared, calcination of Cd(OH)2 without any organic molecule (CdO‐1) and calcination of Cd‐citrate coordination polymer (CdO‐2), to evaluate and compare the toxicity of these two different CdO nanoparticles. Results show that zebrafish exposed to CdO‐2 nanoparticles expressed reduced toxicity as judged by lower oxidative stress levels, rescue of liver carboxylesterases and reduction in metallothionein activity compared to CdO‐1 nanoparticles. Histopathological observations also support our contention that CdO‐1 nanoparticles showed higher toxicity relative to CdO‐2 nanoparticles. The organic unit of Cd‐citrate coordination polymer might have converted into carbon during calcination that might have covered the surface of CdO nanoparticles. This carbon surface coverage can control the release of Cd2+ ions in CdO‐2 compared to non‐covered CdO‐1 nanoparticles and hence mitigate the toxicity in the case of CdO‐2. This was supported by atomic absorption spectrophotometer analyses of Cd2+ ions release from CdO‐1 and CdO‐2 nanoparticles. Thus the present study clearly demonstrates the toxicity of CdO nanoparticles in an aquatic animal and also indicates that the toxicity could be substantially reduced by carbon coverage. This could have important implications in terms of anthropogenic release and environmental pollution caused by Cd and human exposure to Cd2+ from sources such as cigarette smoke. HighlightsToxicity of CdO nanoparticles can be mitigated by the use of sodium citrate.Sodium citrate covers the CdO surface and reduces Cd2+ ion release.Use of sodium citrate reduces both biochemical and histopathological changes.Sodium citrate can be a remediation strategy against CdO nanoparticles toxicity.

Nanostructuring of the carbon macrofiber surface

The method of synthesis of CNF/MF carbon-carbon composites by growing carbon nanofibers (CNFs) on a surface of carbon macrofibres (CMFs) is described. The method is based on catalytic gas-phase deposition of carbon (using C1, C2 hydrocarbons and the mix of C2-C4). Depending on the conditions of modification (composition of catalytic particles, type of hydrocarbon, and temperature), it is possible to obtain CNFs with different morphologies (feathery, fishbone, or platelet fibers). It is found that the modification of MFs by CNFs (0.2–0.3 g/gMF) allows increasing the specific surface area of the initial material in an order of magnitude (up to 25 m2/g). The method is proven to be applicable for the modification of various materials made of CMFs (chopped fibers, tows, and carbon fabric).

Size-segregated emissions and metal content of vehicle-emitted particles as a function of mileage: Implications to population exposure.

The study aims at investigating the characteristics (size distribution, active surface and metal content) of particles emitted by cars as a function of mileage using a novel methodology for characterizing particulate emissions captured by Exhaust Gas Suspension (EGS). EGS was obtained by passing the exhaust gases through a container of deionized water. EGS analysis was performed using laser granulometry, electron scanning microscopy, and high resolution mass spectrometry. Implications of the differences in key features of the emitted particles on population exposure were investigated using numerical simulation for estimating size-segregated PM deposition across human respiratory tract (HRT). It was found that vehicle mileage, age and the respective emissions class have almost no effect on the size distribution of the exhaust gas particulate released into the environment; about half of the examined vehicles with low mileage were found to release particles of aerodynamic diameter above 10 μm. The exhaust gas particulate detected in the EGS of all cars can be classified into three major size classes: (1) 0.1-5 µm - soot and ash particles, metals (Au, Pt, Pd, Ir); (2) 10-30 µm - metal (Cr, Fe, Cu, Zr, Ni) and ash particles; (3) 400-1,000 µm - metal (Fe, Cr, Pb) and ash particles. Newer vehicles with low mileage are substantial sources of soot and metal particles with median diameter of 200 nm with a higher surface area (up to 89,871.16 cm(2)/cm(3)). These tend to deposit in the lower part of the human respiratory tract.

Geophagy in animals and geology of kudurs (mineral licks): a review of Russian publications

This paper reviews from the geological and biological perspectives the achievements of Russian researchers in the field of geophagy, which have not been published in English. It is focused on publications in Russian language about (1) animal behavior related to geophagy, (2) mineral and chemical composition as well as geological characteristics and biological effects of the earths, eaten by animals in various locations in Russia and neighboring countries. The authors argue that the Russian term “solonetz” (salt lick) is too limiting, as animals consume not just salt but many other minerals too. The more general term “kudur” is used for places where animals eat earths. The geological nature and biological properties of kudurites (the common name given to biologically active mineral-crystal substances consumed by animals) and gastroliths (stones consumed by birds and reptiles) are addressed. On the basis of the reviewed data, the authors propose their own views regarding the causes of geophagy.