Review on Zinc Oxide Nanoparticles: Antibacterial Activity and Toxicity Mechanism

Antibacterial activity of zinc oxide nanoparticles(Zn O-NPs) has received significant interest worldwide particularly by the implementation of nanotechnology to synthesize particles in the nanometer region. Many microorganisms exist in the range from hundreds of nanometers to tens of micrometers. Zn O-NPs exhibit attractive antibacterial properties due to increased specific surface area as the reduced particle size leading to enhanced particle surface reactivity. Zn O is a bio-safe material that possesses photo-oxidizing and photocatalysis impacts on chemical and biological species. This review covered Zn O-NPs antibacterial activity including testing methods, impact of UV illumination, Zn O particle properties(size, concentration, morphology, and defects), particle surface modification, and minimum inhibitory concentration. Particular emphasize was given to bactericidal and bacteriostatic mechanisms with focus on generation of reactive oxygen species(ROS) including hydrogen peroxide(H2O2), OH-(hydroxyl radicals), and O2-2(peroxide). ROS has been a major factor for several mechanisms including cell wall damage due to Zn O-localized interaction, enhanced membrane permeability, internalization of NPs due to loss of proton motive force and uptake of toxic dissolved zinc ions.These have led to mitochondria weakness, intracellular outflow, and release in gene expression of oxidative stress which caused eventual cell growth inhibition and cell death. In some cases, enhanced antibacterial activity can be attributed to surface defects on Zn O abrasive surface texture. One functional application of the Zn O antibacterial bioactivity was discussed in food packaging industry where Zn O-NPs are used as an antibacterial agent toward foodborne diseases. Proper incorporation of Zn O-NPs into packaging materials can cause interaction with foodborne pathogens, thereby releasing NPs onto food surface where they come in contact with bad bacteria and cause the bacterial death and/or inhibition.

Toxicity mechanisms of photodegraded polyvinyl chloride nanoplastics on pea seedlings

Nanoplasctics(NPs),which are very small in particle size,exert toxic effect to organisms.Additionally,compared to original NPs,photodegraded NPs would pose higher toxicity.This is because their relatively higher specific surface areas and the presence of additives which can more easily leach.How original NPs and aged NPs affect plant growth has not been widely investigated.This work chose polyvinyl chloride NPs(PVC-NPs)that were subjected to up to 1000 h UV light radiation to explore the impact of PVC-NPs on the growth of pea seedlings(Pisum Sativum L.).The results indicated the existence of PVC-NPs with longer UV light radiation time and higher concentrations had more negative influences on pea seedlings’growth such as germination rate(decreased by 10.6%–22.5%),stem length(decreased by 2.8%–8.1%),dry weight(decreased by 6.3%–7.1%)and fresh weight(decreased by 6.7%–14.8%).It was also noted that photodegraded PVC-NPs resulted in damage to leaf stomata and roots,hindering photosynthesis and absorption of nutrients and hence the decrease in chlorophyll and soluble sugar contents.According to transcriptomic investigation results,the presence of aged PVC-NPs primarily influenced protein processing in endoplasmic reticulum(upregulated metabolic pathway)and phenylpropanoid biosynthesis(downregulated metabolic pathway)of pea seedlings.These results provide an in-depth understanding of how NPs influence the growth of plants.

The bio-distribution,clearance pathways,and toxicity mechanisms of ambient ultrafine particles

Ambient particles severely threaten human health worldwide.Compared to larger particles,ultrafine particles(UFPs)are highly concentrated in ambient environments,have a larger specific surface area,and are retained for a longer time in the lung.Recent studies have found that they can be transported into various extra-pulmonary organs by crossing the air-blood barrier(ABB).Therefore,to understand the adverse effects of UFPs,it is crucial to thoroughly investigate their bio-distribution and clearance pathways in vivo after inhalation,as well as their toxicological mechanisms.This review highlights emerging evidence on the bio-distribution of UFPs in pulmonary and extra-pulmonary organs.It explores how UFPs penetrate the ABB,the blood-brain barrier(BBB),and the placental barrier(PB)and subsequently undergo clearance by the liver,kidney,or intestine.In addition,the potential underlying toxicological mechanisms of UFPs are summarized,providing fundamental insights into how UFPs induce adverse health effects.

Pyrrolizidine alkaloids:An update on their metabolism and hepatotoxicity mechanism

Pyrrolizidine alkaloids(PAs)are among the most hepatotoxic natural compounds that are widely distributed throughout the world.Most PAs are metabolically activated to trigger toxicity.Exposure to herbal medicine containing PAs and food supplements contaminated by PAs is considered to be one of the two main causes of hepatic sinusoidal obstruction syndrome(HSOS),which is a rare hepatic vascular disease with a high mortality rate.PAs-induced HSOS cases have been reported worldwide.However,there is no clinically effective therapy for PAs-induced HSOS,which is partially because the toxic mechanism is not fully understood.This review focuses on updating the information on the metabolism and the molecular mechanisms of PAs hepatotoxicity,including oxidative stress,apoptosis,and dysfunction of bile acid metabolism,and their interactions.

Carbon nanotubes:A review on risks assessment,mechanism of toxicity and future directives to prevent health implication

Carbon nanotubes(CNTs)have tremendous applications in almost every walk of life;however,their harmful impacts on humans and the environment are not well addressed.CNTs have been used in various applications ranging from medical science to different engineering branches,to ease human life.Generally,the toxicological profile of CNTs under laboratory conditions cannot be assessed primarily in medical science due to the inconsistent availability of cytotoxic study data.CNT toxicity has been affected by many physicochemical properties(e.g.,size,type of functionalization),concentration,the extent of exposure,mode of exposure,and even the solvents/medium used to dissolve/disperse CNTs for their application.These inconsistencies arise due to the variation in synthesis methods as well as the mode of their human exposure.Besides their unlimited use in various fields,most of CNT toxicity aspects and mechanisms remain uncertain.Additionally,in-depth knowledge of CNTs toxicity is scarce,and the available literature shows dissimilarities in experimental data and exposure studies.To understand the toxicological issues,it is the need of the hour to provide insight into the published data,post-exposure studies,and various factors that may damage the cells due to CNTs toxicity.This review article analyses the hazardous potential through toxicological implications and summarizes the detailed mechanism(s)of CNTs studied on the different model organisms,including human cell lines.In this review article,we hypothesized that thorough knowledge of various aspects,as mentioned above,helps us design and develop possible strategies to reduce the toxicity of nanomaterial to make them safer and secure for humanity’s betterment.

Based on network pharmacology to explore the mechanism of hepatotoxicity of Fructus Meliae Toosendan

Objective:To explore the potential mechanism of hepatotoxicity induced by Fructus Meliae Toosendan(FMT)through network pharmacology.Methods:The active components and targets of FMT were identified and screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform Database,PubChem Database and Swiss Target Prediction database,etc.Genecards,pharmGKB,and OMIM databases were used to collect relevant targets of hepatotoxicity,and intersect them with the targets of active ingredients to obtain the potential targets of hepatotoxicity caused by FMT.A compound-target network was constructed with Cytoscape 3.8.0 software.The String 11.0 database was used to construct the protein-protein interaction(PPI)network of the targets and to screen out the core targets.In addition,Gene Ontology(GO)terms and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were conducted by R software,and then the pathways directly related to hepatotoxicity were integrated.Results:In this study,9 active ingredients of FMT and 265 targets were obtained.There are 533 hepatotoxicity-related targets,and 76 potential targets for hepatotoxicity caused by FMT,among which quercetin,melianone,and nimbolin A are the key active components for hepatotoxicity caused by FMT,and MYC,STAT3,JUN,and RELA were the core target proteins of FMT’s hepatotoxicity.There were 2353 GO entries(P<0.05),including 2181 Biological Process(BP),41 Cellular Component(CC)and 131 Molecular Function(MF).KEGG enrichment analysis revealed 165 pathways(P<0.05),of which Th17 cell differentiation,HIF-1 signaling pathway,PI3K-Akt signaling pathway were strongly correlated with the hepatotoxicity of FMT.Conclusion:Through network pharmacology,it was found that many potential components in azadirachia chinaberry may be involved in the regulation of apoptosis,excessive inflammatory response and mitochondrial dynamics through multi-target and multi-pathway,resulting in the generation of hepatotoxicity.

Advances in toxicological studies of Radix Phytolaccae

Radix Phytolaccae is the dried root of Phytolacca acinosa Roxb or P.ameri-cana L,which is commonly used as a traditional Chinese medicine to treat diseases like cirrhotic ascites,hepatitis B,nephrotic syndrome,psoriasis,etc.However,there is no exact basis for its clinical application safety.In this paper,the toxic effects and mechanism of Saponin A(EsA),the main component of Radix Phytolaccae,were summarized by searching the results and reports of toxicology related to the plant from 1991 to 2023 on CNKI and pubmed,aiming to provide reference for the toxicological research and future research direction of Radix Phytolaccae,so that Radix Phytolaccae can be safely and effectively used in clinical practice.

Molecular mechanisms underlying the toxicity and detoxification of trace metals and metalloids in plants

Plants take up a wide range of trace metals/metalloids(hereinafter referred to as trace metals)from the soil,some of which are essential but become toxic at high concentrations(e.g.,Cu,Zn,Ni,Co),while others are non-essential and toxic even at relatively low concentrations(e.g.,As,Cd,Cr,Pb,and Hg).Soil contamination of trace metals is an increasing problem worldwide due to intensifying human activities.Trace metal contamination can cause toxicity and growth inhibition in plants,as well as accumulation in the edible parts to levels that threatens food safety and human health.Understanding the mechanisms of trace metal toxicity and how plants respond to trace metal stress is important for improving plant growth and food safety in contaminated soils.The accumulation of excess trace metals in plants can cause oxidative stress,genotoxicity,programmed cell death,and disturbance in multiple physiological processes.Plants have evolved various strategies to detoxify trace metals through cell-wall binding,complexation,vacuolar sequestration,efflux,and translocation.Multiple signal transduction pathways and regulatory responses are involved in plants challenged with trace metal stresses.In this review,we discuss the recent progress in understanding the molecular mechanisms involved in trace metal toxicity,detoxification,and regulation,as well as strategies to enhance plant resistance to trace metal stresses and reduce toxic metal accumulation in food crops.

Exosomes Derived from Hydroquinone-transformed Human Bronchial Epithelial Cells Inhibited Recipient Cell Apoptosis by transferring miR-221

Objective Although benzene is a confirmed environmental carcinogen,the mechanism of its carcinogenicity remains largely unclear.The suggested oncogene,miR-221,is elevated and plays important roles in various tumors,but its role in benzene-induced carcinogenesis remains unknown.Methods In the present study,we constructed hydroquinone(HQ,a representative metabolite of benzene with biological activity)-transformed malignant cell line(16 HBE-t)and analyzed the level of miR-221 in it with qRT-PCR.Exosomes from 16 HBE-t cells incubated with or without an miR-221 inhibitor were isolated by ultracentrifugation,characterized by transmission electron microscopy and laser scanning confocal microscope,and then transfected into 16 HBE cells.The effects of exosomal miR-221 on apoptosis induced by HQ in recipient cells were determined using flow cytometry.Results The amount of miR-221 in 16 HBE-t was significantly increased compared with controls.When recipient cells ingested exosomes derived from 16 HBE-t,miR-221 was increased,and apoptosis induced by HQ was inhibited.Blocking miR-221 in 16 HBE-t using an inhibitor did not significantly alter miR-221 or apoptosis in recipient cells.Conclusion Exosomal miR-221 secreted by 16 HBE-t inhibits apoptosis induced by HQ in normal recipient cells.

Interactions between engineered nanoparticles and dissolved organic matter: A review on mechanisms and environmental effects

Dissolved organic matter（DOM） is ubiquitous in the environment and has high reactivity.Once engineered nanoparticles（ENPs） are released into natural systems, interactions of DOM with ENPs may significantly affect the fate and transport of ENPs, as well as the bioavailability and toxicity of ENPs to organisms. However, because of the complexity of DOM and the shortage of useful characterization methods, large knowledge gaps exist in our understanding of the interactions between DOM and ENPs. In this article, we systematically reviewed the interactions between DOM and ENPs, discussed the effects of DOM on the environmental behavior of ENPs, and described the changes in bioavailability and toxicity of ENPs caused by DOM. Critical evaluations of published references suggest further need for assessing and predicting the influences of DOM on the transport,transformation, bioavailability, and toxicity of ENPs in the environment.

A Comparative Toxicity Study of TiO2 Nanoparticles in Suspension and Adherent Culture Under the Dark Condition

The present study focused on the different acute toxicity of TiO2 nanoparticles（TiO2 NPs） towards the bacteria in suspension culture and adherent culture under the dark conditions. The study investigated the bacteria toxicity with TiO2 NPs at different concentrations（1-2000 mg/L）, sizes（10 nm, 35 nm） and specific surface areas in unit volume solution（0-224 m^2/L） characterized by the cell viability, extracellular polymeric substances（EPS） release and biofilm formation. The bacteria in adherent culture was found to be more resistant against the toxicity of TiO2 NPs compared to that in suspension culture. An NP dose and surface area dependent（rather than the size） bacterial viability was observed in suspension culture, specifically the surface area positively correlated with the toxicity of TiO2 NPs. The size of TiO2 NPs, however, played a more critical role in toxicity of TiO2 NPs in adherent culture. Therefore, the surface area dependent toxicity of TiO2 NPs is a comprehensive parameter describing the dose and size dependent toxicity of TiO2 NPs. The electron microscopic（SEM, TEM, EDX） observations suggested the EPS release and biofilm formation, during aggregation of TiO2 NPs on the bacteria after 12 h cultivation in adherent culture under the dark condition. A possible toxic mechanism could be that ＂effective surface areas＂ that directly contact with the bacterial membrane greatly contributed to the toxicity of TiO2 NPs in both suspension culture and adherent culture. Therefore, as for the possible resistance mechanism, EPS secretion and subsequent biofilm formation may protect the bacteria against the toxicity of TiO2 NPs.

Lipid Profile Altered in Phenanthrene Exposed Zebrafish Embryos with Implications for Neurological Development and Early Life Nutritional Status

Lecithotrophic fish embryos rely on finite maternally deposited yolk resources for early development.Toxicant exposure can disrupt the uptake of yolk resources with consequences for development.In this study,we investigate the impacts of altered yolk utilization on fish embryos using the cardiotoxic compound phenanthrene.Zebrafish embryos were exposed to a cardiotoxic concentration of phenanthrene beginning at 6 hpf(hours post-fertilization)until a maximum of 72 hpf.Embryos were stained with Oil Red O to visualize neutral lipids.We then used a nontargeted approach to profile lipids in 24 and 72 hpf embryos after phenanthrene treatment.To assess changes in lipid movement within the embryo,the yolk sac was dissected from the body at 24 and 72 hpf and analyzed separately from the body at 72 hpf.Overall,total metabolites were significantly reduced in the yolk sac,and staining for neutral lipids was reduced in the embryo body at 72 hpf.This result is consistent with significant reductions in triglycerides in both the embryo body and yolk,indicating a limited contribution of impaired cardiac function to lipid mobilization at the dose tested.Additionally,lysophosphatidylcholines and lysophosphatidylethanolamines were significantly increased in the 72 hpf embryo body.Bioinformatic pathway analysis indicated that changes to these lysophospholipids could be linked to a disease model associated with inflammation and neuron demyelination consistent with previously observed injuries to neuronal and eye development in fish embryos and larvae.

Discussions on Toxic Traditional Chinese Medicine and New Perspectives

Along with the increase in the consumption of traditional Chinese medicine(TCM), the safety of TCM has dramatically attracted the attention and concern of the public. Here, we review previous studies, which focused mainly on the toxicity of toxic TCM and the interpretations for combination, to elaborate on advances and important issues existing in the safety evaluation of TCM, aiming to provide scientific advice for the clinical use. Moreover, we emphasize the importance of a safe evaluation system for TCM based on the material basis for toxicity, which integrates new toxicity testing strategy and is launched under the guidance of TCM theories in future researches.

The chlorination transformation characteristics of benzophenone-4 in the presence of iodide ions

Benzophenone-type UV filters are a group of compounds widely used to protect human skin from damage of UV irradiation. Benzophenone-4（BP-4） was targeted to explore its transformation behaviors during chlorination disinfection treatment in the presence of iodide ions. With the help of ultra performance liquid phase chromatograph and high-resolution quadrupole time-of-flight mass spectrometer, totally fifteen halogenated products were identified, and five out of them were iodinated products. The transformation mechanisms of BP-4 involved electrophilic substitution generating mono-or di-halogenated products,which would be oxidized into esters and further hydrolyzed into phenolic derivatives. The desulfonation and decarboxylation were observed in chlorination system either. Obeying the transformation pathways, five iodinated products formed. The p H conditions of chlorination system determined the reaction types of transformation and corresponding species of products. The more important was that, the acute toxicity had significant increase after chlorination treatment on BP-4, especially in the presence of iodide ions. When the chlorination treatment was performed on ambient water spiked with BP-4 and iodide ions,iodinated by-products could be detected.