Multipollutant reciprocal neurological hazard from smoke particulate matter and heavy metals cadmium and lead in brain nerve terminals.

Heavy metals, Cd2+ and Pb2+, and carbonaceous air pollution particulate matter are hazardous neurotoxicants. Here, a capability of water-suspended smoke particulate matter preparations obtained from poplar wood (WPs) and polypropylene fibers (medical facemasks) (MPs) to influence Cd2+/Pb2+-induced neurotoxicity, and vice versa, was monitored using biological system, i.e. isolated presynaptic rat cortex nerve terminals. Combined application of Pb2+ and WPs/MPs to nerve terminals in an acute manner revealed that smoke preparations did not change a Pb2+-induced increase in the extracellular levels of excitatory neurotransmitter L-[14C]glutamate and inhibitory one [3H]GABA, thereby demonstrating additive result and no interference of neurotoxic effects of Pb2+ and particulate matter. Whereas, both smoke preparations decreased a Cd2+-induced increase in the extracellular level of L-[14C]glutamate and [3H]GABA in nerve terminals. In fluorimetric measurements, the metals and smoke preparations demonstrated additive effects on the membrane potential of nerve terminals causing membrane depolarisation. WPs/MPs-induced reduction of spontaneous ROS generation was mitigated by Cd2+ and Pb2+. Therefore, a potential variety of multipollutant heavy metal-/airborne particulate-induced effects on key presynaptic processes was revealed. Multipollutant reciprocal neurological hazard through disturbance of the excitation-inhibition balance, membrane potential and ROS generation was evidenced. This multipollutant approach and data contribute to up-to-date environmental quality/health risk estimation.

Disposable facemask waste combustion emits neuroactive smoke particulate matter.

Tremendous deposits of disposable medical facemask waste after the COVID-19 pandemic require improvement of waste management practice according to WHO report 2022, moreover facemasks are still in use around the world to protect against numerous airborne infections. Here, water-suspended smoke preparations from the combustion of disposable medical facemasks (polypropylene fibers) were collected; size, zeta potential, surface groups of smoke particulate matter were determined by dynamic light scattering, FTIR and Raman spectroscopy, and their optical properties were characterized. Neurochemical study using nerve terminals isolated from rat cortex revealed a significant decrease in the initial rate of the uptake/accumulation of excitatory and inhibitory neurotransmitters, L-[14C]glutamate and [3H]GABA, and exocytotic release, and also an increase in the extracellular level of these neurotransmitters. Fluorescent measurements revealed that ROS generation induced by hydrogen peroxide and glutamate receptor agonist kainate decreased in nerve terminals. A decrease in the membrane potential of nerve terminals and isolated neurons, the mitochondrial potential and synaptic vesicle acidification was also shown. Therefore, accidental or intentional utilization of disposable medical facemask waste by combustion results in the release of neuroactive ultrafine particulate matter to the environment, thereby contributing to plastic-associated pollution of air and water resources and neuropathology development and expansion.

A comparative multi-level toxicity assessment of carbon-based Gd-free dots and Gd-doped nanohybrids from coffee waste: hematology, biochemistry, histopathology and neurobiology study.

Here, a comparative toxicity assessment of precursor carbon dots from coffee waste (cofCDs) obtained using green chemistry principles and Gd-doped nanohybrids (cofNHs) was performed using hematological, biochemical, histopathological assays in vivo (CD1 mice, intraperitoneal administration, 14 days), and neurochemical approach in vitro (rat cortex nerve terminals, synaptosomes). Serum biochemistry data revealed similar changes in cofCDs and cofNHs-treated groups, i.e. no changes in liver enzymes' activities and creatinine, but decreased urea and total protein values. Hematology data demonstrated increased lymphocytes and concomitantly decreased granulocytes in both groups, which could evidence inflammatory processes in the organism and was confirmed by liver histopathology; decreased red blood cell-associated parameters and platelet count, and increased mean platelet volume, which might indicate concerns with platelet maturation and was confirmed by spleen histopathology. So, relative safety of both cofCDs and cofNHs for kidney, liver and spleen was shown, whereas there were concerns about platelet maturation and erythropoiesis. In acute neurotoxicity study, cofCDs and cofNHs (0.01 mg/ml) did not affect the extracellular level of L-[14C]glutamate and [3H]GABA in nerve terminal preparations. Therefore, cofNHs demonstrated minimal changes in serum biochemistry and hematology assays, had no acute neurotoxicity signs, and can be considered as perspective biocompatible non-toxic theragnostic agent.

Bio-distribution of Carbon Nanoparticles Studied by Photoacoustic Measurements.

Carbon-based nanomaterials are promising for a wide range of biomedical applications, i.e. drug delivery, therapy, and imaging including photoacoustic tomography, where they can serve as contrast agents, biocompatibility and biodistribution of which should be assessed before clinical setting. In this paper, localization of carbon flurooxide nanoparticles, carbon nanodots from ß-alanine, carbon nanodots from urea and citric acid and glucose-ethylenediamine nanoparticles (NPs) in organs of Wistar rats were studied by photoacoustic measurements after 24 h of their intravenous injection. 16 ns light pulse from a Q-switched Nd:YAG laser with 1064 nm wavelength was used as an excitation source. The laser-induced photoacoustic signals were recorded with a ring piezoelectric detector. Light absorption by carbon NPs resulted in noticeable enhancement of the photoacoustic amplitude in the tissues where the NPs were accumulated. The NPs were preferably accumulated in liver, kidneys and spleen, and to a lesser extent in heart and gastrocnemius muscles. Together with remarkable fluorescent properties of the studied carbon nanomaterials, their photoacoustic responses allow their application for bi-modal fluorescence-photoacoustic bio-imaging.

Similar in vitro response of rat brain nerve terminals, colon preparations and COLO 205 cells to smoke particulate matter from different types of wood.

Major source of carbon-containing air born particular matter that significantly pollutes environment and provokes development of neuropathology is forest fires and wood combustion. Here, water-suspended smoke particulate matter preparations (SPs) were synthesized from birch, pine, poplar wood, and also birch bark and pine needles. Taking into account importance of the gut-brain communication system, SP properties were compared regarding their capability to modulate functioning of nerve terminals and gut cells/preparations. In cortex nerve terminals, poplar wood SP was more effective in decreasing uptake and increasing the extracellular levels of excitatory and inhibitory neurotransmitters L-[14C]glutamate and [3H]GABA, respectively. Spontaneous and H2O2-stimulated ROS generation in nerve terminals decreased by SPs, the most efficient one was from poplar wood. SPs from birch, pine and poplar wood caused membrane depolarization, poplar wood SP effect was 5-fold higher vs. birch and pine wood ones. Functional characteristics of gut cells/preparations, which tightly related to nerve terminal experiments, were assessed. SPs increased paracellular permeability of proximal colon mucosal-submucosal preparations monitored in Ussing chamber system (FITC-dextran, 4 kDa), where the most prominent effect had poplar wood SP. The latter demonstrated more considerable influence on COLO 205 cell causing 30 % loss of cell viability. PM emitted to the environment during combustion of various wood caused similar unidirectional harmful effects on brain and gut cell functioning, thereby triggering development of pathologies in gut and brain and gut-brain communication system.

A comparative study of wood sawdust and plastic smoke particulate matter with a focus on spectroscopic, fluorescent, oxidative, and neuroactive properties.

Here, water-suspended smoke aerosol preparation was synthesized from biomass-based fuel, i.e., a widespread product for residential heating, wood sawdust (WP) (pine, poplar, and birch mixture), and its properties were compared in parallel experiments with the smoke preparation from plastics (PP). Molecular groups in the PM preparations were analyzed using Raman and Fourier-transform infrared spectroscopy. WP was assessed in neurotoxicity studies using rat cortex nerve terminals (synaptosomes). Generation of spontaneous and H2O2-evoked reactive oxygen species (ROS) detected using fluorescent dye 2',7'-dichlorofluorescein in nerve terminals was decreased by WP. In comparison with PP, WP demonstrated more pronounced reduction of spontaneous and H2O2-evoked ROS production. WP completely inhibited glutamate receptor agonist kainate-induced ROS production, thereby affecting the glutamate receptor-mediated signaling pathways. WP decreased the synaptosomal membrane potential in fluorimetric experiments and the synaptosomal transporter-mediated uptake of excitatory and inhibitory neurotransmitters, L-[14C]glutamate and [3H] γ-aminobutyric acid (GABA), respectively. PP decreased the ambient synaptosomal level of [3H]GABA, whereas it did not change that of L-[14C]glutamate. Principal difference between WP and PP was found in their ability to influence the ambient synaptosomal level of [3H]GABA (an increase and decrease, respectively), thereby showing riskiness in mitigation of synaptic inhibition by PP and triggering development of neuropathology.

Unique features of brain metastases-targeted AGuIX nanoparticles vs their constituents: A focus on glutamate-/GABA-ergic neurotransmission in cortex nerve terminals.

Gadolinium-based radiosensitizing AGuIX nanoparticles (AGuIX) currently tested two phase 2 clinical trials in association with radiotherapy for the treatment of brain metastases. Here, excitatory/inhibitory neurotransmission was assessed in rat cortex nerve terminals in the presence of AGuIX and their constituents (DOTAGA and DOTAGA/Gd3+) at concentrations used for medical treatment, and those 5-24 times higher. The ambient level, transporter-mediated, tonic and exocytotic release of L-[14C]glutamate and [3H]GABA, the membrane potential of nerve terminals were not changed in the presence of AGuIX at concentrations used for medical treatment ([Gd3+] = 0.25 mM, corresponding to 0.25 g.L-1), and DOTAGA (0.25 mM) and DOTAGA/Gd3+ (0.25 mM/0.01 mM). Difference between AGuIX and the precursors was uncovered, when their concentrations were increased. AGuIX (1.25-6 mM) did not change any transport characteristics of L-[14C]glutamate and [3H]GABA, whereas, DOTAGA (1.25-6 mM) affected the membrane potential, ambient level, and exocytotic release of L-[14C]glutamate and [3H]GABA. Gd3+ did not mask, but even enhanced above effects of DOTAGA. Therefore, AGuIX did not influence glutamate- and GABA-ergic neurotransmission at the presynaptic site. In contrast, DOTAGA and mixture DOTAGA/Gd3+ significantly affected synaptic neurotransmission at high concentrations. AGuIX own structure that overcomes neurotoxic features of their constituents.

Transient coating of γ-Fe2O3 nanoparticles with glutamate for its delivery to and removal from brain nerve terminals.

Glutamate is the main excitatory neurotransmitter in the central nervous system and excessive extracellular glutamate concentration is a characteristic feature of stroke, brain trauma, and epilepsy. Also, glutamate is a potential tumor growth factor. Using radiolabeled ʟ-[14C]glutamate and magnetic fields, we developed an approach for monitoring the biomolecular coating (biocoating) with glutamate of the surface of maghemite (γ-Fe2O3) nanoparticles. The nanoparticles decreased the initial rate of ʟ-[14C]glutamate uptake, and increased the ambient level of ʟ-[14C]glutamate in isolated cortex nerve terminals (synaptosomes). The nanoparticles exhibit a high capability to adsorb glutamate/ʟ-[14C]glutamate in water. Some components of the incubation medium of nerve terminals, that is, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) and NaH2PO4, decreased the ability of γ-Fe2O3 nanoparticles to form a glutamate biocoating by about 50% and 90%, respectively. Only 15% of the amount of glutamate biocoating obtained in water was obtained in blood plasma. Albumin did not prevent the formation of a glutamate biocoating. It was shown that the glutamate biocoating is a temporal dynamic structure at the surface of γ-Fe2O3 nanoparticles. Also, components of the nerve terminal incubation medium and physiological fluids responsible for the desorption of glutamate were identified. Glutamate-coated γ-Fe2O3 nanoparticles can be used for glutamate delivery to the nervous system or for glutamate adsorption (but with lower effectiveness) in stroke, brain trauma, epilepsy, and cancer treatment following by its subsequent removal using a magnetic field. γ-Fe2O3 nanoparticles with transient glutamate biocoating can be useful for multifunctional theranostics.

Plastic smoke aerosol: Nano-sized particle distribution, absorption/fluorescent properties, dysregulation of oxidative processes and synaptic transmission in rat brain nerve terminals.

Smoke from plastic waste incineration in an open air travels worldwide and is a major source of air pollution particulate matter (PM) that is very withstand to degradation and hazard to human health. Suspension of smoke aerosol components in water occurs during rains and fire extinguishing. Here, water-suspended plastic smoke aerosol (WPS) preparations suitable for biotesting were synthesized. It has been revealed using dynamic light scattering that WPS contained major nano-sized (∼30 nm) PM fraction, and this result was confirmed by electron microscopy. Optical absorption of WPS was in the UV region and an increase in λex led to a red-shift in fluorescence emission with a corresponding decrease in fluorescence intensity. WPS was analyzed in neurotoxicity studies in vitro using presynaptic rat cortex nerve terminals (synaptosomes). Generation of spontaneous reactive oxygen species (ROS) detected using fluorescent dye 2',7-dichlorofluorescein in nerve terminals was decreased by WPS (10-50 µg/ml) in a dose-dependent manner. WPS also reduced the H2O2-evoked ROS production in synaptosomes, thereby influencing cellular oxidative processes and this effect was similar to that for carbon nanodots. WPS (0.1 mg/ml) decreased the synaptosomal membrane potential and synaptic vesicle acidification in fluorimetric experiments. WPS (1.0 mg/ml) attenuated the synaptosomal transporter-mediated uptake of excitatory and inhibitory neurotransmitters, L-[14C]glutamate and [3H]GABA, respectively. This can lead to an excessive increase in the glutamate concentration in the synaptic cleft and neurotoxicity via over activation of ionotropic glutamate receptors. Therefore, WPS was neurotoxic and provoked presynaptic malfunction through changes of oxidative activity, reduction of the membrane potential, synaptic vesicle acidification, and transporter-mediated uptake of excitatory and inhibitory neurotransmitters in nerve terminals. In summary, synthesis and emission to the environment of ultrafine PM occur during combustion of plastics, thereby polluting air and water resources, and possibly triggering development of neuropathologies.

Membrane action of polyhexamethylene guanidine hydrochloride revealed on smooth muscle cells, nerve tissue and rat blood platelets: A biocide driven pore-formation in phospholipid bilayers.

A well-known cationic biocide of guanidine polymer family, polyhexamethylene guanidine hydrochloride (PHMG) has been tested against smooth muscle cells isolated from swine myometrium, synaptosomes of rat brain nerve terminals and rat blood platelets for the membrane action. It was established that PHMG blocked the activity of Na+,K+-ATPase of smooth muscle cells plasma membrane by 82.2 ±â€¯0.9% at a concentration of 7 ppm, whilst a dose-dependent depolarization of synaptosomes and platelets became appreciable at 100-500 ppm. Comparative studies by the methods of mass spectrometry (MALDI-TOF and PDMS-TOF), viscosimetry, dynamic light scattering and model phospholipid membranes revealed PHMG oligomers with various number of repeat units (8-16) that formed K+-selective potential-dependent pores in sterol-free phosphatidylethanolamine-containing phospholipid bilayers at a concentration of 1 ppm. Obtained results suggest that besides acidic lipids and membrane proteins phosphatidylethanolamine and cholesterol are the other major factors responsible for the differences between PHMG-induced plasma membrane depolarization of microbial and eukaryotic cells and thus, diverse modes of PHMG membrane action.

Effect of O-methyl-ß-cyclodextrin-modified magnetic nanoparticles on the uptake and extracellular level of l-glutamate in brain nerve terminals.

Changes in cholesterol concentration in the plasma membrane of presynaptic nerve terminals nonspecifically modulate glutamate transport and homeostasis in the central nervous system. Reduction of the cholesterol content in isolated rat brain nerve terminals (synaptosomes) using cholesterol-depleting agents decreases the glutamate uptake and increases the extracellular level of glutamate in nerve terminals. Extraction of cholesterol from the plasma membrane and its further removal from the synaptosomes by external magnetic field can be achieved by means of magnetic nanoparticles with immobilized cholesterol-depleting agent such as O-methyl-ß-cyclodextrin (MCD). A simple approach is developed for preparation of maghemite (γ-Fe2O3) nanoparticles containing chemically bonded MCD. The method is based on preparation of a silanization agent containing MCD. It is synthesized by the reaction of triethoxy(3-isocyanatopropyl)silane with MCD. Base-catalyzed silanization of superparamagnetic γ-Fe2O3 provides a relatively stable colloid product containing 48µmol of MCDg-1. MCD-modified γ-Fe2O3 nanoparticles decrease the initial rate of the uptake and accumulation of l-[14C]glutamate and increase the extracellular l-[14C]glutamate level in the preparation of nerve terminals. The effect of MCD-immobilized nanoparticles is the same as that of MCD solution; moreover, magnetic manipulation of the nanoparticles enables removal of bonded cholesterol.