Toxic Impact Research Articles

Unraveling Copper Imbalance in Autism Spectrum Disorder: Mechanistic Insights from the Valproic Acid Mouse Model.

Abnormal copper (Cu) levels are often closely associated with neurological disorders including neurodevelopmental conditions, such as autism spectrum disorder (ASD). However, the mechanisms underlying the disruption of Cu homeostasis in critical organs, such as the brain, remain unclear. In this study, we elucidated the molecular mechanisms of Cu imbalance in the brain of a valproic acid (VPA) mouse model along with the changes in specific metabolites. Significant alterations occurred in proteins associated with primary Cu-related metabolism in specific regions of the brain (prefrontal cortex, amygdala, cerebellum, and hippocampus), resulting in a direct elevation of Cu ions within the brain tissues (control: 5.05 ± 0.61 μg/g vs model: 6.28 ± 0.81 μg/g, p = 0.015). Furthermore, the brain metabolic profiles revealed significant upregulation of lipids, particularly phospholipid metabolites. Typical neurotransmitters, for example, dopamine (DA) (p < 0.0001) and serotonin (5-HT) (p = 0.02) were upregulated in amygdala. Other small metabolites like glutathione (GSH) (p = 0.0004) also exhibited notable variation in brain. The potential impact of Cu toxicity on the signaling pathways of key metabolites was then evaluated, providing new insights into the role of Cu in metabolism of neurotransmitters in the brain. Our finding sheds molecular aberrations associated with essential element metabolism in the brain, providing new elemental perspectives for understanding the pathogenic mechanisms underlying ASD.

Environmental assessment of gasification and green hydrogen potential role in waste management decarbonization

Achieving sustainability involves implementing a circular economy model and decarbonizing the waste management sector. The development of innovative technologies that enable the reduction of emissions and resource recovery is one of the sector's greatest challenges. From this perspective, the waste-to-methanol (WtM) process represents a viable prospect, the potential environmental impacts of which have never been studied from a life-cycle perspective. A cradle-to-grave LCA analysis was conducted, studying WtM technology and its potential implementation of green hydrogen (WtM-GH) in the process, through a comparison with traditional waste-to-energy (WtE).The results showed that WtM-GH performs best for global impacts, with a global warming potential of 3.52·107 kgCO2eq instead of 1,04·108 kgCO2eq proper of the WtE. Positive effects take place also for the fossil resource scarcity. Looking for non-toxic regional/local impacts WtE represents the best scenario, with the best performance on water consumption (7.96·107 m3) and ionising radiation (2.82·107 kBq Co-60eq). Cumulative impact results, obtained through the normalization, found that WtM is the best scenario, thanks to the less toxic impact compared to the other two, especially for freshwater ecotoxicity (5.26·106 kg 1,4-DCB) and marine ecotoxicity (6.73·106 kg 1,4-DCB).WtM-GH allows the production of 1366 kg of methanol per ton of Refuse Derived Fuel, thanks to the conversion of the entire CO2 contained in the waste, enhancing the value of by-products and carbon credits on the market and making the process more economically sustainable.

Increased adsorption of diflubenzuron onto polylactic acid microplastics after ultraviolet weathering can increase acute toxicity in the water flea (Daphnia magna)

The ultraviolet (UV) weathering of microplastics (MPs) can lead to higher adsorption of harmful contaminants, thus increasing the potential risks of their combined effects. Because biodegradable MPs are more susceptible to UV weathering than conventional MPs, concerns have arisen about their ecological toxicity and environmental impact. Therefore, this study investigated the mechanisms associated with the adsorption of the pesticide diflubenzuron (DFB) onto polylactic acid (PLA) MP particles after UV weathering and the acute effects (48 h) of their combination on the water flea Daphnia magna. These effects were also compared with those of the conventional MP polyethylene terephthalate (PET). UV weathering led to a greater number of cracks and pores in the PLA particles compared to PET, as well as a higher number of oxygen-based functional groups and a larger surface area. These surface changes in UV-weathered PLA particles promoted higher DFB adsorption, which in turn led to stronger acute toxicity for D. magna compared to UV-weathered PET particles. Combined exposure to 25 ng L−1 DFB and both UV-weathered and non-UV-weathered MPs significantly reduced the chitin content in D. magna, while combined exposure to 12.5 ng L−1 DFB and the MPs increased the chitin content. This effect was more pronounced for UV-weathered PLA exposure than UV-weathered PET exposure. The expression of the genes for chitinase and endocrine glycoprotein, both of which are closely associated with the toxic mechanisms of DFB, showed no significant changes with the combination of 25 ng L−1 DFB and non-UV-weathered MPs but were significantly downregulated after UV weathering. Overall, the UV weathering of PLA promoted the adsorption of DFB, thus increasing its toxic effects. Our findings demonstrate the importance of considering the effects of UV weathering and interactions with environmental pollutants when assessing the ecological risks associated with biodegradable MPs.

Evaluating toxic impact on marine microbial community using combined genetic and phenotypic approaches.

Preserving the oceans is a major challenge for the twenty-first century. In 2000, the Water Framework Directive harmonized European regulations on water management to protect and restore the good ecological status of aquatic ecosystems, including the marine environment. This study aims to address the need to understand how pollutants affect marine ecosystems, particularly microbial communities, which are vital for ecosystem balance and biogeochemical cycling. By combining genetic and phenotypic approaches, we aimed to predict the long-term ecological effects of marine pollution and develop improved management strategies. We used microcosms to expose a marine microbial community to various toxicant (anthracene, benzene, chlorpyrifos, copper chloride, and PFOA) and combined phenotypic and genetic approaches to assess i) changes in community structure, ii) phenotypic responses to pollutant, and iii) the benefits of integrating these methods to better evaluate the impact of pollutants on microbial communities and ecosystem services. The obtained results highlight a certain functional resilience despite a significant effect on genetic diversity. Moreover, only specific exposure conditions, such as higher pollutant concentrations, appear to significantly affect ecosystem functions. Leveraging this knowledge, the future challenge will be to develop a straightforward biosensor to estimate and predict the impact of pollutants on these ecosystems, in order to better protect them.

Hepatotoxicological Evaluation of Parsonsia straminea (R.Br) F. Muel Stem Bark Crude Extract in Mice

Background: Toxicity is defined as the degree to which a substance can harm humans or animals. In reality, every entity that makes substances is undoubtedly labeled poisonous except it is quantified to make safety certain for therapeutic purposes. Herbal medicines are generally considered to be safe and efficacious among people of various ethnic backgrounds globally. The plant Parsonsia straminea has been traditionally claimed to be used in arthritis and seizures, although it is not widely explored. P. straminea a plant used medicinally cannot be said to be free from toxicity owing to fact on its use. Aim of the Study: The aim of the study is to assess the potential hepatotoxicity of P. straminea stem bark extract in mice Methodology: For the study, about thirty rodents (mice) were set into six groups with five (5) mice in each group. The study groups (GPs) include 1=0.2ml/kg of distilled water as control; 2 to 6=50,100,200,400 and 800 mg/kg of P. straminea extract. The harvested tissues were sent for histopathological examination. Results: This study has proven that the extract relatively impacted no significant toxicity on the liver enzymes such as alanine aminotransferase (ALT), alkaline phosphatase (ALP), albumin (ALB) aspartate aminotransferase (AST) and total protein (TP). Conclusion: The study findings have shown that the ethanolic stem bark of P. straminea possesses relatively no remarkable toxicity impact on the liver as revealed in the liver enzymes and the histology assessment.

Pilot Study on a Liquid Mineral Foliar Fertilizer Mixed with Herbicides for Maize Protection and Nutrition

The purpose of this study was to develop a complex composition of a foliar liquid mineral fertilizer containing NPK macroelements and microelements including Fe, Mg, B, S, Zn, Cu, Mo, Ni, V, and Cr. This complex fertilizer aims to support the optimal development and maturation of maize crops, thereby enhancing both the quality and quantity of production. In our study, an original recipe was established for a complex composition of foliar liquid mineral fertilizer, and a technological process was developed in order to obtain the recipe at the laboratory level. The designed fertilizer was a complex mixture of fertilizers with herbicides with multiple purposes, which can be used in different pedo-climatic areas and which present, at the same time, low toxicity and minimal ecological impact. A wide-spectrum mixture DICOPUR TOP containing 2,4-D acid and Dicamba was chosen as a systemic herbicide which is absorbed by plants both in the root system and also on the leaves. For conditioning the complex mixture of fertilizers with herbicides, different types of polyvinyl alcohol with different degrees of hydrolysis were used. The liquid fertilizer mixture with DICOPUR TOP was applied over two years (2021 and 2022) to the Felix maize hybrid, demonstrating significant positive effects on grain yield while effectively controlling both dicotyledonous and monocotyledonous weeds.

A spatiotemporal model for the effects of toxicants on the competitive dynamics of aquatic species

In this paper, we develop a reaction–diffusion model with negative toxicant–taxis that incorporates spatiotemporally inhomogeneous toxicant input to investigate the impact of toxicants on the competitive dynamics of two species in a polluted aquatic environment. Here the negative toxicant–taxis models the evasive movement of avoiding toxicants by species. We establish the global well-posedness of the model, analyze the existence and stability of spatially homogeneous steady states, and derive sufficient conditions for species extinction and coexistence. Through linear stability analysis, we identify sufficient conditions on model parameters that destabilize spatially homogeneous steady states under spatiotemporally uniform toxicant input. Numerical experiments reveal the influence of key toxicant-related factors (input rate, taxis intensity, and diffusivity) on competition outcomes and species distributions. Notably, strong negative toxicant–taxis can induce spatial aggregation and segregation patterns between the species and the toxicant under uniform toxicant input. Our findings suggest that toxicant–taxis may promote population persistence and coexistence, particularly when the toxicant input is not uniform in space and time and the toxicant does not diffuse fast (i.e. weak diffusivity). However, strong toxicant diffusion can diminish the impact of taxis, adversely affecting population persistence and species coexistence.

Lead Nitrate (Pb(NO3)2) Toxicity Effects on DNA Structure and Histopathological Damage in Gills of Common Carp (Cyprinus carpio).

The toxic impact of environmentally relevant nominal sub-lethal concentration of lead nitrate (23 mg/L) on the gills of Cyprinus carpio after 30 days of exposure was assessed. Structural alterations were analyzed through histopathology, and the DNA damage rate in peripheral erythrocytes was evaluated by alkaline comet assay. A significant deviation in the gill histoarchitecture was observed compared to the control group. Significant changes, including the curling of secondary lamellae, loss of filaments, necrosis, hyperplasia, hypertrophy of cells of primary filament, and vacuolization, were found in the fish exposed to nominal sub-lethal concentration of lead nitrate. Moreover, the comet assay showed lead nitrate-induced DNA damage, evidenced by the length of the DNA "tail" in the exposed fish. The findings of this study strongly indicated that lead nitrate, even at sub-lethal levels, could significantly alter the overall physiology of the fish. This situation could lead to severe ecological consequences.

Value of Serum Retinol-Binding Protein, Lipoprotein A and Inflammatory Nutritional Indexes and their Interactions in Predicting Acute Kidney Injury after Coronary Angiography

Background: Contrast-induced acute kidney injury (CI-AKI) is a serious condition that can arise after undergoing coronary angiography (CAG). This complication is primarily caused by the toxic impact of contrast agents on the kidneys, along with oxidative stress and inflammatory responses. Identifying reliable biomarkers for early prediction remains essential due to the limited accuracy of existing clinical risk scores. Methods: This retrospective case-control study included 365 patients undergoing CAG between December 2021 and December 2023. Patients were categorized into non-AKI (n = 320) and AKI (n = 45) groups based on post-procedural renal function. Biomarkers including serum retinol-binding protein (RBP), lipoprotein A (Lp(a)), interleukin-6 (IL-6), and nutritional markers were measured. Baseline demographics, lipid profiles, and procedure details were recorded. Results: Baseline characteristics revealed no significant differences between groups in terms of age, BMI, gender, and prevalence of hypertension or diabetes mellitus. Notably, RBP (41.83 ± 10.22 mg/L vs. 32.45 ± 8.76 mg/L, p &lt; 0.001), Lp(a) (42.35 ± 13.87 mg/dL vs. 35.76 ± 11.54 mg/dL, p &lt; 0.001), and IL-6 (6.23 ± 2.14 pg/mL vs. 4.87 ± 1.59 pg/mL, p &lt; 0.001) levels were significantly higher in the AKI group. Total protein levels were significantly lower in the AKI group (6.88 ± 0.62 g/dL vs. 7.12 ± 0.54 g/dL, p = 0.006). Multivariate logistic regression identified RBP (OR 1.118, 95% CI 1.072–1.166, p &lt; 0.001), Lp(a) (OR 1.047, 95% CI 1.014–1.080, p = 0.005), and IL-6 (OR 1.710, 95% CI 1.355–2.157, p &lt; 0.001) as independent predictors of AKI, while higher total protein levels were protective (OR 0.497, 95% CI 0.257–0.960, p = 0.037). Conclusion: Serum RBP, Lp(a), IL-6, and total protein levels are valuable biomarkers for predicting CI-AKI after CAG. Elevated RBP, Lp(a), and IL-6 indicate higher risk, while higher total protein suggests protective effects.

Financial toxicity of total cancer care immunotherapy patients and caregivers: impacts of COVID-19 pandemic and inflation.

Financial toxicity, cancer-treatment-related financial harm, is associated with expensive treatments like immunotherapy. The purpose of this study was to explore financial toxicity among advanced cancer patients receiving immunotherapies and their caregivers and, secondarily, to study how recent inflation and the COVID-19 pandemic impacted these experiences. Advanced cancer patients receiving immunotherapies and their caregivers were recruited to participate in semi-structured interviews about supportive care needs from 2022 to 2023. The Comprehensive Score for Financial Toxicity was collected. Guided by Jones et al.'s cancer financial toxicity model, the content analysis was conducted by two trained coders using NVIVO R1. Sixteen patients and 10 caregivers (including 7 dyads) across 5 states participated in interviews in 2022-2023. Participants averaged 63.43years (SD = 12.75), and patients received an average of 14.6months of immunotherapy (SD = 9.415). The majority lived in non-metropolitan areas (67%) and were white (95%). Three theory-driven themes were developed: (1) Sources of Financial Toxicity, (2) Buffers of Financial Toxicity, and (3) Consequences of Financial Toxicity. Inflation was added to financial toxicity for non-metropolitan dwelling participants due to increased prices of gas and accommodation. Social support systems buffered the impact of financial toxicity. Material and psychological impacts of financial toxicity disproportionately affected younger and privately insured participants. While immunotherapy patients face high medical costs of treatment, the burdens of accessing treatment for people living at a distance from the cancer center can exacerbate financial toxicity. Clinicians and researchers should also consider external financial pressures such as national economic impacts that compound the financial toxicity of treatment.

Mass layoffs at BYJU’S – founder’s dilemma

Learning outcomes This case study provides students/managers an opportunity to learn about the following: to infer the challenges involved in the downsizing of employees; to asses and evaluate BYJU’S organizational culture; and to determine the impact of workplace toxicity. Case overview/synopsis The focus of this case is the controversy faced by BYJU’S due to its mass layoffs and toxic work culture. This case discusses the CEO’s dilemma in resolving the controversy. Two rounds of mass layoffs at BYJU’S are discussed in detail. The industrial dispute filed by Employees Union against BYJU’S accusing it of denying due compensation to laid-off employees is also discussed. This case consists of a section explaining the toxic work culture at BYJU’S, which is supported by employee complaints. The CEO’s justification and apology have been illustrated in this case. The case ends with a closing dilemma and challenges faced by the CEO. Complexity academic level The case is best suited for undergraduate students studying Human Resources Management subjects in Commerce and Business Management streams. The authors suggest that the instructor inform students to read the case before attending the 90-min session. It can be executed in the classroom after discussing the theoretical concepts. Supplementary material Teaching notes are available for educators only. Subject code CSS 6: Human Resource Management.

Theories into Practice: Building Youth Resilience through School-Community-University Partnerships

This paper describes the theoretical grounding of the Pontiac Resilience Project, a subproject of an established community-university partnership. The goal of the Pontiac Resilience Project is to reduce the toxic impact of trauma and Adverse Childhood Experiences (ACEs); support children’s healthy development; and create a healing resilient community of Pontiac. Our work critically examines the intersectionality of ACEs and childhood trauma as rooted in systemic inequities and historical racism. Grounded in critical ecological perspectives, we outline the praxis and pedagogy underlying our youth efforts of the Pontiac Resilience Project, conducted in partnership with a public school district, to inform and mobilize youths. Through a relationship-based participatory approach, youths, ages 15-18, are empowered as community change agents.

TUDY OF CHRONIC TOXICITY OF AN IMPROVED A-SILICONE IMPRESSION MATERIAL PRODUCED IN UKRAINE

The objective of this study is to evaluate the potential toxic effects of an improved A-silicone impression material with decorative properties on the organs and mucous membranes of laboratory animals. Materials and Methods The experiment was conducted on white laboratory rats aged 9 months and weighing 230–285 g. Findings indicate that prolonged contact (30 days) with the material does not result in significant changes in the function of major organ systems in these laboratory rats. Results. A single exposure of laboratory rats to A-silicone impression material with disinfectant properties did not cause significant changes in the physiological state of the animals. Weights of internal organs, including the liver, spleen, heart, and adrenal glands, remained within normal limits, indicating that the material had no toxic effects. The analysis of the peripheral blood composition did not reveal any abnormalities in the number of red blood cells, leukocytes, hemoglobin and other cellular components. The functional state of the liver and kidneys, including the activity of the enzymes AlаT and AсаT, levels of total protein, albumin, creatinine and urea, remained stable and did not change under the influence of the material. There was also no effect on carbohydrate metabolism. No abnormalities in protein synthesis and nitrogen excretion functions were detected, which confirms the safety of the material during the 30-day observation. Conclusion. It was established that this material in the tested dose does not affect the enzyme-synthetic function of the liver and does not exhibit cytolytic effects. The material was found to have no toxic impact on liver function with prolonged use, nor does it cause statistically significant deviations in the measured indicators between the control and experimental groups. The absence of sugar, ketones, and protein in the urine indicates no adverse effect on the renal nitrogen-excreting and saluretic functions, as well as on the vital organs of the rats.

Comparative study of the stabilizing behavior of organoclays in Pickering emulsion

Pickering Emulsions are commonly applied in the pharmaceutical, food, and chemical industries. The use of natural particles as stabilizers provides access to surfactant-free dispersions with reduced toxicity and environmental impact. This work investigates the use of three commercial organoclays (C15A, C10A, and C30B) and hydrophilic sodium montmorillonite (Mt) as stabilizers for Pickering emulsions. Emulsion stability was evaluated through macroscopic and microscopic morphological observations and the emulsion microstructure was characterized by optical microscopy and DLS measurements to assess creaming and coalescence. The influence of different experimental parameters on emulsion stability was evaluated, including organoclay content, emulsification time, emulsification speed, and oil–water ratio. The results showed that emulsions based on C15A exhibit better stability against coalescence as compared to emulsions prepared with the other clays. This was attributed to the wettability of the particles and solution viscosity. Droplet size decreased as emulsification time and stabilizer content increased and reached a minimum value at 1 wt.% of C15A and for emulsification time of 5 min and oil–water ratio O/W (v/v: 50/50). The experimental parameters also impacted emulsion viscosity, increasing it for high clay content and as the stirring speed and emulsification time increased. The results of the heat and cold resistance stability tests indicated that 25 °C represents the optimal storage temperature for the prepared emulsions.

Cyclophosphamide-induced multiple organ dysfunctions: unravelling of dose dependent toxic impact on biochemistry and histology.

Cyclophosphamide, an immunosuppressive alkylating agent, has been used against breast cancer, lymphoma and myeloid leukemia. Despite various therapeutic uses, its toxic impacts on multiple organs remains to be fully elucidated. This study aimed to investigate dose dependent toxic impact of cyclophosphamide on liver, kidney, brain and testis emphasizing serum and tissue biochemical and histological alterations. Experimental design consisted of five groups of albino rats. Group 1-5 were administered vehicle for five consecutive days. On 6th day, group 1 received vehicle only and termed as control; group 2-5 received cyclophosphamide through intraperitoneal route at the rate of 50, 100, 150 and 200mg/kg dose, respectively. After 24h of the last administration, rats were euthanised; serum and tissue biochemistry; histology, sperm count and its motility were performed. Serological, biochemical and histological indices exhibited dose dependent deviations from their regular status as a marker of toxicity in liver, kidney, brain and testis. Tukey's HSD post hoc test revealed maximum damage in multiple organs with 200mg/kg dose of cyclophosphamide.

Build-a-Bio-Strip: An Online Platform for Rapid Toxicity Assessment in Chemical Synthesis.

The increasing need to understand and control the environmental impact of chemical processes has revealed the challenge in efficient evaluation of toxicity of the vast number of chemical compounds and their varying effects on biological systems. In this study, we introduce "Build-a-bio-Strip", a novel online service designed to carry out a quick initial analysis of the toxic impact of chemical processes. This platform enables users to automatically generate toxicity characteristics of chemical reactions using their own data on cytotoxicity or median lethal doses of the substances involved or computational predictions based on SMILES strings. The service calculates the toxicity metrics such as bio-Factors and cytotoxicity potentials, which can be used to identify the substances with significant contributions to the overall toxicity of a particular process. This facilitates the selection of safer synthetic routes and the optimization of chemical processes from a toxicity perspective. "Build-a-bio-Strip" represents a step toward safer and more sustainable chemical practices. It is available free-of-charge at http://app.ananikovlab.ai:8080/.

Biodiversity of Diatoms as Indicators of Water Quality and Landscape Sustainable Dynamics in the Zarafshan River, Uzbekistan

For the first time, we have compiled a general list of diatoms for the Zarafshan River consisting of 428 species based on our own research and the literature data. Indicator species for nine water parameters were identified, making up more than 90% of the list. Bioindicators and statistical methods revealed that sections of the river around the city of Samarkand and further in the middle reaches reflect the complexity of the impact of the environment on diatom communities. The surveyed sections of the middle reaches of the river are divided into branches and the dynamics of water parameters and diatom communities are shown from the border with Tajikistan to the confluence of the Zarafshan with the Amu Darya. The indices of organic pollution, S, and toxic impact, WESI, were calculated. They show that there is an increase in salinity and turbidity and a decrease in organic pollution downriver. At the same time, the Navoi section is a source of water acidification. Nutrients and heavy metals, as well as phenol pollution, enter the river from various sources, mainly in the middle reaches of the river. The Zarafshan Nature Reserve in the catchment area of the upper section of the river within Uzbekistan is important for maintaining water quality. Bioindicators show an increase in self-purification, with an increase in the species richness and abundance of diatoms in the middle section of the Zarafshan River. The integrated index of river pollution, RPI, shows that most pollution comes from the northern canal of the river in the middle reaches. A general look at the Zarafshan River catchment basin and the dynamics of the identified water parameters and bioindicator species of diatoms shows that the river ecosystem successfully copes with incoming pollution, including transboundary impacts from Tajikistan. Such a conclusion could not be made based on chemical analysis of the water alone. This allowed us to recommend expanding state monitoring points to the lower section of Karakul while including biological indicators in the observations.

Transcriptomic Analysis of the Protective Effect of Piperine on Orlistat Hepatotoxicity in Obese Male Wistar Rats.

Obesity is a risk factor for the development of noncommunicable diseases that impair the quality of life. Orlistat is one of the most widely used drugs in the management of obesity due to its accessibility and low cost. However, cases of hepatotoxicity have been reported due to the consumption of this drug. On the other hand, piperine is an alkaloid found in black pepper that has demonstrated antiobesity, antihyperlipidemic, antioxidant, prebiotic, and hepatoprotective effects. The aim of this study was to evaluate the protective effect of piperine on the toxicity of orlistat in liver tissue. Obese male rats were administered piperine (30 mg/kg), orlistat (60 mg/kg), and the orlistat-piperine combination (30 mg/kg + 60 mg/kg) daily for 6 weeks. It was observed that the orlistat-piperine treatment resulted in greater weight loss, decreased biochemical markers (lipid profile, liver enzymes, pancreatic lipase activity), and histopathological analysis showed decreased hepatic steatosis and reduction of duodenal inflammation. Transcriptomic analysis revealed that the administration of piperine with orlistat increased the expression of genes related to the beta-oxidation of fatty acids, carbohydrate metabolism, detoxification of xenobiotics, and response to oxidative stress. Therefore, the results suggest that the administration of orlistat-piperine activates signaling pathways that confer a hepatoprotective effect, reducing the toxic impact of this drug.

The Combination of Buparvaquone and ELQ316 Exhibit a Stronger Effect than ELQ316 and Imidocarb Against Babesia bovis In Vitro.

Background/Objectives: Bovine babesiosis is a vector-borne disease transmitted by ticks that causes important losses in livestock worldwide. Recent research performed on the drugs currently used to control bovine babesiosis reported several issues including drug resistance, toxicity impact, and residues in edible tissue, suggesting the need for developing novel effective therapies. The endochin-like quinolones ELQ-316 and buparvaquone (BPQ) act as cytochrome bc1 inhibitors and have been proven to be safe and efficacious against related apicomplexans, such as Plasmodium spp. and Babesia microti, without showing toxicity in mammals. The objectives of this study are investigating whether ELQ-316, BPQ, and their combination treatment could be effective against Babesia bovis in an in vitro culture model and comparing with imidocarb (ID), the routinely used drug. Methods: In vitro cultured parasites starting at 2% percentage of parasitemia (PPE) were treated with BPQ, ELQ-316, ID, and the combinations of BPQ + ELQ-316 and ID + ELQ-316 at drug concentrations that ranged from 25 to 1200 nM, during four consecutive days. The IC50% and IC99% were reported. Parasitemia levels were evaluated daily using microscopic examination. Data were compared using the non-parametrical Mann-Whitney and Kruskall-Wallis test. Results: All drugs tested, whether used alone or in combination, significantly decreased the survival (p < 0.05) of B. bovis in in vitro cultures. The combination of BPQ + ELQ-316 had the lowest calculated inhibitory concentration 50% (IC50%) values, 31.21 nM (IC95%: 15.06-68.48); followed by BPQ, 77.06 nM (IC95%: 70.16-86.01); ID + ELQ316, 197 nM (IC95%:129.0-311.2); ID, 635.1 nM (IC95%: 280.9-2119); and ELQ316, 654.9 nM (IC95%: 362.3-1411). Conclusions: The results reinforce the higher efficacy of BPQ at affecting B. bovis survival and the potential synergistic effects of its combination with ELQ-316, providing a promising treatment option against B. bovis.

Evaluating the impact of the combined acute toxicity of iron (Fe) and microplastics on Namalycastis jaya

The rising concern over heavy metals (HMs) and microplastics (MPs) pollution in marine ecosystems, primarily driven by anthropogenic activities, poses significant threats to ecological health. Understanding the combined exposure of HMs and MPs aids in toxicity assessment. In this study, we examined the combined effects of polystyrene microplastics (MPs) and iron (Fe) on oxidative stress, bioaccumulation, histopathology, and genotoxicity in Namalycastis jaya. Oxidative stress was assessed by analyzing the levels of Superoxide dismutase (SOD), Catalase (CAT), Peroxidase (POD), Malondialdehyde (MDA), and Bicinchoninic acid (BCA), while genotoxicity was evaluated using the comet assay. Bioaccumulation analysis, conducted via Inductively coupled plasma-optical emission spectrometry (ICP-OES), indicated that the highest values (4.790 µg/ml) were observed in combined exposure, emphasizing the significant increase in iron (Fe) accumulation in polychaetes facilitated by MPs. Biochemical analysis revealed that oxidative damage in polychaetes became evident within 48 h of exposure to individual contaminants. However, in the case of combined exposures, elevated stress levels were observed within just 24 h. The genotoxic assay further demonstrated a higher degree of DNA damage in the combined exposure compared to individual exposures. Similarly, histopathology revealed mild alterations in the gut epithelium in combined exposures. It is evident that MPs intensify both oxidative and DNA damage induced by Fe in polychaetes. The insights gained from this study provide valuable information for the risk assessment of Fe and MPs in environmental safety, contributing to our understanding of the complex interactions between these pollutants in marine ecosystems.