Toxicological Effects Research Articles

The male reproductive toxicity after 5-Fluorouracil exposure: DNA damage, oxidative stress, and mitochondrial dysfunction in vitro and in vivo

5-Fluorouracil (5-FU), a chemotherapeutic drug used to treat a variety of cancers, can enter the environment through different routes, causing serious public health and environmental concerns. It has been reported that 5-FU exposure adversely affects male reproductive function, and its effects on this system cannot be avoided. In this study, using western blotting and quantitative polymerase chain reaction studies, we found that 5-FU promoted testicular injury by inducing oxidative stress, which was accompanied by the inhibition of nuclear factor erythroid 2-related factor 2/antioxidant response element signaling. Accumulation of reactive oxygen species (ROS) aggravated 5-FU-mediated mitochondrial dysfunction and apoptosis in murine cell lines and testes, indicating oxidative stress and mitochondrial-dependent apoptotic signaling play crucial roles in the damage of spermatogenic cells caused. N-Acetyl-L-cysteine, an antioxidant that scavenges intracellular ROS, protected spermatogenic cells from 5-FU-induced oxidative damage and mitochondrial dysfunction, revealing the important role of ROS in testicular dysfunction caused by 5-FU. We found that 5-FU exposure induces testicular cell apoptosis through ROS-mediated mitochondria pathway in mice. In summary, our findings revealed the reproductive toxicological effect of 5-FU on mice and its mechanism, provided basic data reference for adverse ecological and human health outcomes associated with 5-FU contamination or poisoning.

Oxidative stress and DNA alteration on the earthworm Eisenia fetida exposed to four commercial pesticides.

Modern agriculture is mainly based on the use of pesticides to protect crops but their efficiency is very low, in fact, most of them reach water or soil ecosystems causing pollution and health hazards to non-target organisms. Fungicide triazoles and strobilurins based are the most widely used and require a specific effort to investigate toxicological effects on non-target species. This study evaluates the toxic effects of four commercial fungicides Prosaro® (tebuconazole and prothioconazole), Amistar®Xtra (azoxystrobin and cyproconazole), Mirador® (azoxystrobin) and Icarus® (Tebuconazole) on Eisenia fetida using several biomarkers: lipid peroxidation (LPO), catalase activity (CAT), glutathione S-transferase (GST), total glutathione (GSHt), DNA fragmentation (comet assay) and lysozyme activity tested for the first time in E. fetida. The exposure to Mirador® and AmistarXtra® caused an imbalance of ROS species, leading to the inhibition of the immune system. AmistarXtra® and Prosaro®, composed of two active ingredients, induced significant DNA alteration, indicating genotoxic effects. This study broadened our knowledge of the effects of pesticide product formulations on earthworms and showed the need for improvement in the evaluation of toxicological risk deriving from the changing of physicochemical and toxicological properties that occur when a commercial formulation contains more than one active ingredient and several unknown co-formulants.

Modeling polycyclic aromatic hydrocarbons (PAHs) concentrations from wildfires in California

In recent years, wildfires in California have increased in frequency and intensity due to climate change and prolonged drought. The air pollutants released by wildfires cause significant health consequences, among which polycyclic aromatic hydrocarbons (PAHs) are particularly toxic. Estimating PAH emissions from wildfires is challenging due to variability in vegetation types. In this study, we estimate PAH emission rates across California at a high resolution, based on laboratory-measured PAH emission rates from 22 different vegetation types and detailed vegetation mapping. By combining these estimates with biomass burning data from the NCAR Fire Inventory, the Community Multiscale Air Quality Modeling System simulates PAH concentrations for the 2017 fire season. The modeling results compare favorably to measurements from three PAH monitoring sites in California. The peak PAH emissions from wildfire events are up to be 80 times higher in the gas phase and 32 times higher in the particle phase compared to a case without fire emissions. The population-weighted PAH concentrations from the fire case (0.053 µg/m3) are 47 % higher compared to a non-fire case (0.036 µg/m3) in the particle phase and 11 % higher in the gas phase (9.82 ppt compared to 8.83 ppt) during the study period. While highly depended on the meteorological condition, the simulated spatial distribution indicates that gas-phase PAHs are less likely to travel long distances from the fire source and are prone to aging into the particle phase during transport. Consequently, populations are more likely to be exposed to particle-phase PAHs during wildfire events. This finding has important implications for understanding the health impacts of wildfire-induced PAH concentrations, as particle-phase PAHs may have different toxicological effects compared to gas-phase PAHs.

Thiadiazole/Thiadiazine Derivatives as Insecticidal Agent: Design, Synthesis, and Biological Assessment of 1,3,4-(Thiadiazine/Thiadiazole)-Benzenesulfonamide Derivatives as IGRs Analogues against Spodoptera littoralis.

In keeping with our investigation, a simple and practical synthesis of novel heterocyclic compounds with a sulfamoyl moiety that can be employed as insecticidal agents was reported. The compound 2-hydrazinyl-N-(4-sulfamoylphenyl)-2-thioxoacetamide 1 was coupled smoothly with triethylorthoformate or a variety of halo compounds, namely phenacyl chloride, chloroacetyl chloride, chloroacetaldehyde, chloroacetone, 1,3-dichloropropane, 1,2-dichloroethane, ethyl chloroformate, 2,3-dichloro-1,4-naphthoquinone, and chloroanil respectively, which afforded the 1,3,4-thiadiazole and 1,3,4-thiadiazine derivatives. The new products structure was determined using elemental and spectral analysis. Under laboratory conditions, the biological and toxicological effects of the synthetic compounds were also evaluated as insecticides against Spodoptera littoralis (Boisd.). Compounds 3 and 5 had LC50 values of 6.42 and 6.90 mg/L, respectively. The investigated compounds (from 2 to 11) had been undergoing molecular docking investigation for prediction of the optimal arrangement and strength of binding between the ligand (herein, the investigated compounds (from 2 to 11)) and a receptor (herein, the 2CH5) molecule. The binding affinity within docking score (S, kcal/mol) ranged between -8.23 (for compound 5), -8.12 (for compound 3) and -8.03 (for compound 9) to -6.01 (for compound 8). These compounds were shown to have a variety of binding interactions within the 2CH5 active site, as evidenced by protein-ligand docking configurations. This study gives evidence that those compounds have 2CH5-inhibitory capabilities and hence may be used for 2CH5-targeting development. Furthermore, the three top-ranked compounds (5, 3, and 9) and the standard buprofezin were subjected to density functional theory (DFT) analysis. The highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) energy difference (ΔE) of compounds 5, 3, and 9 was found to be comparable to that of buprofezin. These findings highlighted the potential and relevance of charge transfer at the molecular level.

Evaluation of enrofloxacin in the Chinese soft-shelled turtle (Pelodiscus sinensis) based on the biochemical, histopathological and intestinal microbiota responses

Enrofloxacin (ENR) is a veterinary medicine extensively used in aquatic farming, the abuses of antibacterials can lead to drug residues and toxicity to aquatic animals. Nevertheless, its toxicological effects on the Pelodiscus sinensis remain unclear. The objective of this work was to study the toxic effects of ENR on male P. sinensis following multiple oral administration. For hematological, antioxidant status, histological and ultrastructural analyzed, male P. sinensis were orally administrated with ENR for 5 consecutive days, each at the dose of 15 (recommended dose, 1×), 45 (3 times the recommended dose, 3×), and 75 (5 times the recommended dose, 5×) mg/kg body weight (BW) daily. The effect of ENR on P. sinensis by changes in the intestinal microbiota using high-throughput sequencing technology was also investigated. Samples of blood and fresh tissue (liver, spleen, intestine, muscle, spermary, testes, heart, lung, and kidney) were collected after 24 h of drug withdrawal. The results showed that multiple oral administration of ENR induced immunosuppression (lowered total proteins, alkaline phosphatase, and albumin), hepatic-renal dysfunction (elevated aspartate transaminase, alanine aminotransferase, urea nitrogen, K+ and Ca2+), and lowering the hepatic and splenic antioxidant functions (higher MDA, and declines in the activities of SOD, CAT, and NOS) in 3× ENR-dosed or 5× ENR-dosed groups. Noteworthy, histopathological and ultrastructural examination of tissue samples revealed adverse effects with increasing oral dosage of ENR. The 16S sequencing analysis showed that the ENR treatment can greatly change the intestinal microbial diversity and abundance in P. sinensis, but more probiotics such as Cetobacterium, Lactococcus, and Paraclostridium were retained in the short-term period. The findings may provide new insights into the toxicity of ENR to P. sinensis, and help to determine the dose to ensure the safety of aquatic food products.

Aminomethylphosphonic Acid (AMPA), a Glyphosate Metabolite, Decreases Plasma Cholinesterase Activity in Rats

Glyphosate, a widely used herbicide, is linked to a plethora of deleterious effects in both clinical and preclinical studies. Nevertheless, the effects of its main metabolite, aminomethylphosphonic acid (AMPA), whose half-life in soil is even longer than that of glyphosate, have been little explored. On this basis, as a first approach, in this work, we report that intraperitoneal (i.p.) administration of AMPA or glyphosate (at 10, 56, and 100 mg/kg) decreased, to a similar extent, plasma cholinesterase (ChE) activity in acutely exposed rats. Moreover, we designed an experimental protocol to analyze and compare the effects of AMPA and glyphosate on human plasma ChE activity; this protocol consisted of adding these compounds to human plasma to subsequently test the effects of this plasma on the contraction to acetylcholine (ACh) in the frog rectus abdominis muscle (an indirect estimate of ChE activity). Accordingly, this muscular contraction to ACh was evaluated before and after pre-incubation of ACh with (i) plasma alone, (ii) plasma with AMPA, and (iii) plasma with glyphosate. Our results indicate that AMPA, like glyphosate, decreased ChE activity in the plasma of rats (when given i.p.) and humans (when added in vitro), suggesting that both xenobiotics may exert similar toxicological effects.

Developmental toxicity and mechanism of polychlorinated biphenyls 126 and nano-polystyrene combined exposure to zebrafish larvae

3,3′,4,4′,5-Pentachlorobiphenyl (PCB126) is the most toxic congener of dioxin-like polychlorinated biphenyls (DL PCBs), while nanoplastics (NPs) have recently emerged as significant marine pollutants, both posing threats to aquatic organisms and human health. They coexist in the environment, but their comprehensive toxicological effects remain unclear. In this study, zebrafish embryos were simultaneously exposed to PCB126 and 80-nanometer nanoplastyrene (NPS). Researchers utilized fluorescence microscopy, qPCR, histopathological examination, and transcriptomic sequencing to investigate the developmental toxicity of different concentrations of PCB126 and NPS individually or in combination on zebrafish embryos and larvae. Results indicate that the chorion significantly impedes the accumulation of NPS (p < 0.05). It is noteworthy that this barrier effect diminishes upon simultaneous exposure to PCB126. In this experiment, the semi-lethal concentration of PCB126 for larvae was determined to be 6.33 μg/L. Exposure to PCB126 induces various deformities, primarily mediated through the aryl hydrocarbon receptor (AHR). Similarly, exposure to NPS also activates AHR, leading to developmental impairments. Furthermore, transcriptomic sequencing revealed similar effects of PCB126 and NPS on the gene expression trends in zebrafish larvae, but combined exposure to both exacerbates the risk of cancer and induces more severe cardiac toxicity. At this level, co-exposure to PCB126 and NPS adversely affects the development of zebrafish larvae. This study contributes to a deeper understanding of the in vivo accumulation of DL polychlorinated biphenyls and microplastics in actual aquatic environments and their impact on fish development.

Potentialities of Tannase-Treated Green Tea Extract in Nutraceutical and Therapeutic Applications.

Green tea has garnered widespread interest in the past decades due to its content of health-beneficial polyphenols and catechins, besides reportedly exhibiting activities for the prevention, and possibly treatment, of many modern-life-associated afflictions. Hence, the functional food potential of health-beneficial beverages such as green tea is widely and commercially promoted. Biotransformation of green tea extract using enzymes such as tannase ostensibly enhances its beneficial well-being properties and disease-preventing functionalities. The tannase-treated green tea catechins may exhibit enhanced, amongst others, antioxidant, anti-tumour, anti-wrinkle, anti-inflammatory, anti-obesity and anti-sarcopenia properties compared to native green tea extract. Nonetheless, the health benefits and therapeutic and toxicological effects associated with these compounds, before and after tannase treatment, present a scientific gap for detailed studies. Accordingly, the review surveys the literature from the late twentieth century until the year 2023 related to the aforementioned important aspects.

Applications of quartz crystal microbalance with dissipation in nanomedicine (QCM-D): a personal experience

Due to their unique physical and chemical properties, the potential application of nanomaterials in medicine is partic¬ularly attractive. Despite the many advantages that nanomaterials can offer as diagnostic and therapeutic tools, their transition from the bench to clinical practice is extremely challenging. One of the many barriers that nanomedicines may encounter is their toxicological effect. In fact, the development of novel nanomaterials / nanoparticles must pro¬ceed always in tandem with the assessment of any potential toxicological effects associated to them. Once nano¬materials reach the systemic circulation, they interact with endothelial cells, plasma proteins, and other blood compo¬nents. There is no doubt that the study of nanomaterials-blood interactions is crucial to warrant the biocompatibility of nanomaterials developed for human use.

Bisphenol a (BPA) aggravate the adverse effect on physiological and biochemical response in freshwater mussel potomida littoralis

ABSTRACT Bisphenol A (BPA) is a chemical compound extensively employed in plastic manufacturing, and this pollutant has been detected in diverse aquatic organisms, notably bivalves. In order to comprehend the ecological and toxicological consequences of BPA Bisphenol A in these organisms, it is essential to examine the physiological and biochemical effects and identify areas where our understanding is lacking. This knowledge is crucial for determining the environn ental threat posed by bisphenol A and assisting decision-makers in establishing the appropriate priorities. This investigation aimed to assess the impact of BPA on the biochemical and physiological parameters of the freshwater mussel Potomida littoralis. In a laboratory setting, mussels were subjected to two different levels of BPA (20 and 100 μg/L) for a duration of 21 days. Filtration rate was calculated from the clearance of neutral red, fed to mussels at different BPA concentrations. The mussel’s filtration rate capacity declined as BPA exposure intensified, potentially due to the mussel’s attempt to close its valves and minimize BPA absorption, thus preventing cellular damage. In the digestive gland tissue, key antioxidant and detoxification defenses, including catalase (CAT) activity, glutathione-S-transferase (GST) activity, and levels of H2O2 and glutathione (GSH), were activated, particularly at the 100 μg/L BPA concentration. This activation helped protect against lipid damage at higher BPA concentrations. This study underscores the significance of preventing and regulating BPA release into the environment to avert detrimental consequences for aquatic ecosystems.

Histological Disruptive Effects of Tau-Fluvalinate in Zebrafish (Danio rerio) Testis

Due to the high use of pesticides, undesirable effects are observed in the environment and toxic effects occur in terrestrial and aquatic organisms via pesticide bioaccumulation. Although bioaccumulation levels are low, especially in aquatic ecosystems, toxicological effects on aquatic organisms have been observed. Synthetic pyrethroids are pesticides produced for domestic and agricultural pests and tau-fluvalinate is also a broad-spectrum synthetic pyrethroid. Our study investigated the histopathological effects of zebrafish exposed to tau-fluvalinate at two different doses (8µg/L,16µg/L) on testicular tissue. After 5 days of exposure, testicular tissues were dissected and routine histological methods were applied. Tissues were investigated under a light microscope after they were stained with hematoxylin &amp; eosin. As a result of tau-fluvalinate exposure, deterioration in seminiferous tubule morphology, interstitial fibrosis, vascular congestion, karyorrhexis and hypertrophic spermatogenic cells were detected. Tau-fluvalinate exposure was found to induce apoptosis and cause germ cell deterioration.

Chronic toxicity of sediment-bound triclosan on freshwater walking catfish Clarias magur: Organ level accumulation and selected enzyme biomarker responses

Triclosan (TCS) is a biocide widely used in personal care and medicinal products. TCS persists in sediments and has been detected worldwide, making sediments a vital route of TCS exposure to aquatic organisms. This experiment explored the bioaccumulation and toxicological effects of TCS-contaminated sediment. The study revealed that the half-life of TCS in the sediment-water system was 21.52 days. Exposure of Clarias magur juveniles to 0.4 and 0.8 mg kg−1 TCS-spiked sediment resulted in high Biota-Sediment Accumulation Factor (BSAF) with the highest bioaccumulation in the liver (29.62–73.61 mg kg−1), followed by gill (9.22–17.57 mg kg−1), kidney (5.04–9.76 mg kg−1), muscle (2.63–4.87 mg kg−1) and brain (1.53–3.20 mg kg−1). Furthermore, a concentration-dependent increase in oxidative stress biomarkers such as superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST) was documented during 45 days of exposure in gill, liver, kidney, muscle, and brain tissues of exposed fish. A similar increasing trend was also recorded for liver transaminase enzymes such as glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) during the experimental period compared to control. Serum biochemical analysis revealed a significant time and concentration-dependent increase in serum glucose, serum GOT, and serum GPT, while serum total protein and albumin decreased significantly during exposure. These findings demonstrate high bioaccumulative and toxic nature of TCS in fish, promoting multiple physiological and biochemical dysfunctions through sediment exposure. The study underscores the urgent need for strengthened regulations and robust monitoring of triclosan across various environmental matrices, including sediment, to mitigate the detrimental impacts of TCS effectively.

Toxicological Effects of Commonly Used Mosquito Coil Smoke on Liver and Lung Function in Rats

The utilization of mosquito coils as a household-level strategy for mosquito control is widely practiced in malaria-endemic regions spanning Africa, Asia, and South America. However, the continuous application of mosquito coils has prompted significant apprehensions concerning environmental and health implications. This research aims to evaluate the potential hepatic and pulmonary toxicities associated with the inhalation of mosquito coil smoke in rat subjects over both sub-chronic and chronic durations. A questionnaire was used to make inquiries regarding the prevalent types and brands of mosquito coils employed, the manner in which they are used, the durations for which they are utilized. A total of twenty-four albino rats were categorized into three distinct groups: the control group and two exposed groups. These groups were subjected to distinct brands of mosquito coil smoke across two distinct exposure regimens – a sub-chronic exposure lasting 4 weeks and a chronic exposure spanning 12 weeks. Following the exposure periods, blood samples were collected for the analysis of serum-based and biochemical markers, including serum aspartate aminotransferase (AST), alanine aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), bilirubin, serum bicarbonate, and Lactate dehydrogenase (LDH), oxygen saturation, C-reactive protein, total protein, and microscopic analysis of lung tissue and liver tissue. The histopathological analysis of lung tissue was appropriately included. However, the analysis of liver tissue was omitted. The results demonstrated a significant elevation in the levels of these biochemical markers among the exposed rats in comparison to the control group. Concurrently, a decrease in blood oxygen saturation was noted in the exposed rats when contrasted with the control group. Conversely, the serum concentrations of high-sensitivity C-reactive protein, total protein, and alanine aminotransferase (ALT) did not exhibit notable differences in relation to the control group. Additionally, microscopic analysis of lung tissue indicated the presence of histopathological lesions in the exposed rats, suggesting a detrimental impact of mosquito coil smoke exposure in a time-dependent progression.

Chromium levels in placental tissue and neural tube defects: Association and mechanistic study

Human exposure to chromium (Cr) is common but little is known about its adverse effects on pregnancy outcomes. This study aimed to explore the association between Cr exposure and the risk of neural tube defects (NTDs) and the underlying mechanisms of Cr-induced NTDs. 593 controls and 408 NTD cases with placentas were included in this study. Chromium trichloride (Cr(III)) and potassium dichromate (Cr(VI)) were intragastrically administered to pregnant mice and the number of NTDs was recorded. The odds ratio for total NTDs in the highest exposure group in placenta was 4.18 (95% confidence interval (CI), 1.97–8.84). The incidence of fetal NTDs in mice administered with Cr(III) showed a dose-response relationship. Cr(VI) didn't show teratogenicity of NTDs whereas increased the stillbirth rate. Prenatal exposure to Cr(III) increased levels of oxidative stress and apoptosis in fetal mice. RNA-sequencing results indicated significant enrichment of the MAPK pathway. RT-qPCR and Western blot analysis revealed that Cr(III) induced increased expression of p-JNK, p-P38, and Casp3. Toxicological effects can be partly antagonized by antioxidant supplementation. High chromium exposure was associated with increased human NTD risks. Excessive Cr(III) exposure can induce NTDs in fetal mice by increasing apoptosis through upgrading oxidative stress and then activating JNK/P38 MAPK signaling pathway.

Influence of para-substituted benzaldehyde derivatives with different push/pull electron strength groups on the conformation of human serum albumin and toxicological effects in zebrafish

Excessive intake of benzaldehyde and its derivatives can cause irreversible damage to living organisms. Hence, benzaldehyde derivatives with different para-substitutions of push/pull electronic groups were chosen to investigate the effect of different substituent properties on the structure of human serum albumin (HSA). The binding constants, number of binding sites, major interaction forces, protein structural changes, and binding sites of benzaldehyde (BzH) and its derivatives (4-BzHD) with HSA in serum proteins were obtained based on multispectral and molecular docking techniques. The mechanism of BzH/4-BzHD interaction on HSA is mainly static quenching and is accompanied by the formation of a ground state complex. BzH/4-BzHD is bound to HSA in a 1:1 stoichiometric ratio. The interaction forces for the binding of BzH/4-BzHD to HSA are mainly hydrogen bonding and hydrophobic interaction, which are also accompanied by a small amount of electrostatic interactions. The effect of BzH/4-BzHD on HSA conformation follows: 4-Diethylaminobenzaldehyde (4-DBzH) > 4-Nitrobenzaldehyde (4-NBzH) > 4-Hydroxybenzaldehyde (4-HBzH) > 4-Acetaminobenzaldehyde (4-ABzH) > BzH, which means that the stronger push/pull electronic strength of the para-substituted benzaldehyde derivatives has a greater effect on HSA conformation. Furthermore, the concentration-lethality curves of different concentrations for BzH/4-BzHD on zebrafish verified above conclusion. This work provides a scientific basis for the risk assessment of benzaldehyde and its derivatives to the ecological environment and human health and for the environmental toxicological studies of benzaldehyde derivatives with different strengths of push/pull electron substitution.

Revolutionizing healthcare: Harnessing nano biotechnology with zinc oxide nanoparticles to combat biofilm and bacterial infections-A short review

A crucial pathogenic mechanism in many bacterial diseases is the ability to create biofilms. Biofilms are suspected to play a role in over 80 % of microbial illnesses in humans. In light of the critical requirement for efficient management of bacterial infections, researchers have explored alternative techniques for treating bacterial disorders. One of the most promising ways to address this issue is through the development of long-lasting coatings with antibacterial properties. In recent years, antibacterial treatments based on metallic nanoparticles (NPs) have emerged as an effective strategy in the fight over bacterial drug resistance. Zinc oxide nanoparticles (ZnO-NPs) are the basis of a new composite coating material. This article begins with a brief overview of the mechanisms that underlie bacterial resistance to antimicrobial drugs. A detailed examination of the properties of metallic nanoparticles (NPs) and their potential use as antibacterial drugs for curing drug-sensitive and resistant bacteria follows. Furthermore, we assess metal nanoparticles (NPs) as powerful agents to fight against antibiotic-resistant bacteria and the growth of biofilm, and we look into their potential toxicological effects for the development of future medicines.

Unravelling the microplastic menace: different polymers additively increase bee vulnerability

Microplastics (MPs) are growing and ubiquitous environmental pollutants and represent one of the greatest contemporary challenges caused by human activities. Current research has predominantly examined the singular toxicological effects of individual polymers, neglecting the prevailing reality of organisms confronted with complex contaminant mixtures and potential synergistic effects. To fill this research gap, we investigated the lethal and sublethal effects of two common MPs, polystyrene (PS - 4.8-5.8 μm) and poly(methyl methacrylate) (PMMA - 1-40 μm), and their combination (MIX), on the pollinating insect Apis mellifera. For each treatment, we evaluated the oral toxicity of two ecologically relevant and one higher concentration (0.5, 5 and 50 mg/L) and analysed their effects on the immune system and worker survival. As immune activation can alter the cuticular hydrocarbon profile of honey bees, we used gas chromatography-mass spectrometry (GC-MS) to investigate whether MPs lead to changes in the chemical profile of foragers and behavioural assay to test whether such changes affect behavioural patterns of social recognition, undermining overall colony integrity. The results indicate an additive negative effect of PS and PMMA on bee survival and immune response, even at ecologically relevant concentrations. Furthermore, alterations in cuticle profiles were observed with both MPs at the highest and intermediate concentrations, with PMMA being mainly responsible. Both MPs exposure resulted in a reduction in the abundance of several cuticular compounds. Hive entry guards did not show increased inspection or aggressive behaviour towards exposed foragers, allowing them to enter the colony without being treated differently from uncontaminated foragers. These findings raise concerns not only for the health of individual bees, but also for the entire colony, which could be at risk if contaminated nestmates enter the colony undetected, allowing MPs to spread throughout the hive.

Mechanism of Apoptosis in Porcine Ovarian Granulosa Cells Triggered by T-2 Toxin

T-2 toxin (T-2), an A-type mono mycotoxin produced by various Fusarium species, disrupts DNA/RNA and protein synthesis upon entering the body, resulting in pathological conditions in various tissues/organs and posing a significant threat to human and animal health. However, the mechanisms underlying its toxicity remain unclear. With the goal of learning how T-2 affects reproduction in animals, we utilized primary porcine ovarian granulosa cells (pGCs) as a carrier in vitro and constructed concentration models for analyzing cell morphology and RNA-sequencing (RNA-seq). Our findings showed that T-2 could influence pGCs morphology, induce cell cycle arrest, and promote apoptosis in a dose-dependent manner. The results of RNA-seq analyses indicated that a total of 8216 genes exhibited significant differential expression (DEG) following T-2 treatment, of which 4812 were observed to be down-regulated and 3404 were up-regulated. The DEGs following T-2 toxin treatment of pGCs had a notable impact on many metabolic pathways such as PI3K-Akt, Ras, MAPK, and apoptosis, which in turn altered important physiological processes. Gene set enrichment analysis (GSEA) indicated that the differences in the harmful effects of T-2 might be caused by the varying control of cellular processes and the pathway responsible for steroid metabolism. These results present further insights regarding the mechanism of T-2 action on sow reproductive toxicity, enhance our understanding of T-2 reproductive toxicological effects, and lay a theoretical foundation for the judicious prevention of T-2-induced reproductive toxicity.

Dessecting the Toxicological Profile of Polysorbate 80 (PS80): Comparative Analysis of Constituent Variability and Biological Impact Using a Zebrafish Model

Polysorbate 80, commonly abbreviated as PS80, is a widely used pharmaceutical excipient renowned for its role as a solubilizer and stabilizer in drug formulations. Although PS80 is essential for various pharmaceutical applications, particularly in the formulation of injectable drugs, it has been implicated in a range of adverse reactions. However, due to the complexity of the composition of PS80, the differences in the types and contents of the constituents of PS80 from different manufacturers increase the probability or likelihood of their uneven quality.Addressing the complete spectrum of PS80′s components is challenging; thus, most studies to date have examined PS80 as a singular entity. This approach, however, carries a degree of uncertainty, as it overlooks the unique composition and concentration of components within the PS80 used in experiments, which may not reflect the actual diversity in commercially available PS80 products.Recognizing the critical need to understand how PS80′s composition influences biological effects and toxicity, our study aims to bridge this knowledge gap. By doing so, we can clarify how different PS80 compositions from various manufacturers might affect the quality of pharmaceutical formulations, and also guide excipient manufacturers toward producing higher-quality PS80. Such insights could further facilitate a more targeted application of PS80 in drug development.Building on our previous work, we isolated and prepared two key components of PS80—polyoxyethylene sorbitan monooleate (PSM) and polyoxyethylene isosorbide monooleate (PIM)—and conducted a systematic comparison. We evaluated the acute, hemolytic, and target organ toxicity of two different PS80 samples, as well as PSM and PIM, using a zebrafish model. Our research also delved into the potential mechanisms behind the observed toxicological effects, providing an in-depth understanding of PS80′s impact on biological systems.The results show that PS80, PSM, and PIM resulted in developmental anomalies in larval zebrafish. The primary organs of acute toxicity in zebrafish exposed to PS80 and its typical components PSM and PIM include the cardiovascular system, kidneys, intestines, skin, and liver. Notably, PIM further induced severe pericardial edema and erythrocyte hemolysis, thereby affecting blood flow. The samples also instigated oxidative damage by disrupting the redox equilibrium in the larvae. Compared to PS80, both PSM and PIM induced greater oxidative damage, with PIM notably causing significantly higher lipid oxidation, suggesting that oxidative stress may play a crucial role in polysorbate80-induced toxicity. Furthermore, our study found that PS80 could induce alterations in DNA conformation. The findings underscore the necessity for excipient regulators to establish comprehensive quality standards for Polysorbate 80 (PS80). By implementing such standards, it is possible to minimize the clinical risks associated with the variability in PS80 composition, ensuring safer pharmaceutical products for patients.

Assessing the effects of a commercial fungicide and an herbicide, alone and in combination, on Apis mellifera: insights from biomarkers and cognitive analysis

Agrochemicals play a vital role in protecting crops and enhancing agricultural production by reducing threats from pests, pathogens and weeds. The toxicological status of honey bees can be influenced by a number of factors, including pesticides. While extensive research has focused on the lethal and sublethal effects of insecticides on individual bees and colonies, it is important to recognise that fungicides and herbicides can also affect bee health. Unfortunately, in the field, honey bees are exposed to mixtures of compounds rather than single substances. This study aimed to evaluate the effects of a commercial fungicide and a commercial herbicide, both individually and in combination, on honey bees. Mortality assays, biomarkers and learning and memory tests were performed, and the results were integrated to assess the toxicological status of honey bees. Neurotoxicity (acetylcholinesterase and carboxylesterase activities), detoxification and metabolic processes (glutathione S-transferase and alkaline phosphatase activities), immune system function (lysozyme activity and haemocyte count) and genotoxicity biomarkers (nuclear abnormalities assay) were assessed. The fungicide Sakura® was found to activate detoxification enzymes and affect alkaline phosphatase activity. The herbicide Elegant 2FD and the combination of both pesticides showed neurotoxic effects and induced detoxification processes. Exposure to the herbicide/fungicide mixture impaired learning and memory in honey bees. This study represents a significant advance in the understanding of the toxicological effects of commonly used commercial pesticides in agriculture and contributes to the development of effective strategies to mitigate their adverse effects on non-target insects.