Poisoning Research Articles

Toxicity Assessment of Ethanol Extract of Saussurea lappa (Costus) Root in Male Wistar Rats

: Background and Objective: Saussurea lappa is a medicinal plant that has been used in the treatment of various disease conditions for decades. Researchers have provided diversified characteristics of this medicinal plant, enormous data about the bioactive compounds and as well its pharmacological properties. However, information regarding toxicity study of Saussurea lappa root is lacking. The acute and sub-chronic toxicity of Saussurea lappa root ethanolic extract was investigated in this study using an in vivo model (male Wistar rats). Materials and Method: The acute toxicity study was done in two phases: Phase One comprised four groups of three rats each which were administered with 50 mg, 100 mg and 1600 mg per kg bodyweight ethanolic extract of S. lappa while the last group (control) was given water and normal fed once. Phase Two involved administering 1600 mg, 2900 mg and 5000 mg per bodyweight. The median lethal dose of the plant was determined in the acute toxicity study. In sub-chronic toxicity studies, the effects of S. lappa root ethanol extract in daily single oral administration at the doses of 200, 400 and 800 mg/kg during 28 days were determined. The blood haematological and biochemical parameters as well as the histopathological examination of the liver and kidneys were studied. Results: In acute study, a single administration of the Saussurea lappa root ethanolic extract up to a dose of 5000 mg/kg did not cause mortality of animals all through the study. Thus, the median lethal dose (LD50) of Saussurea lappa root ethanolic extract was greater than 5000 mg/kg. Saussurea lappa root ethanolic extract caused no significant effect in the haematological and biochemical parameters of the treated groups when compared to the control. There were also no noticeable histological changes in the liver and kidneys of the Saussurea lappa treated rats compared to controls.. Conclusion: These results have shown that oral administration of Saussurea lappa root ethanol extract did not yield any significant toxic effect when acutely and daily administered for 28 days in the male Wistar rats. Hence, Saussurea lappa root ethanol extract could be regarded as a safe natural product for therapeutic use.

Evaluation of Sedative activity of Cannabis Sativa in mice

Background: Cannabis sativa Linn. (Family: Cannabaceae) is commonly cultivated in Bangladesh in moist areas such as riverbanks, lakes, canals, and roadsides. The leaves of this plant are traditionally used to treat insomnia, depression, and neurodegenerative diseases. Objective: The study's objective is to investigate the sedative effects and phytochemical composition of the Cannabis sativa species in Nigeria. Methods: The elevated plus maze was used to assess the sedative effect of various fractions of aqueous methanol extracts of Cannabis sativa at a dosage of 100 mg/kg in mice. Comparisons were made between the sedative action of the extract and diazepam, which was used as the positive control. Additionally, acute toxicity was also evaluated during the assessment. Results: During the elevated plus-maze test, various parameters such as the number of entries in open arms and the number of entries in closed arms were recorded. The administration of different fractions of aqueous methanol extracts of Cannabis sativa resulted in a significant increase (p < 0.001) in the time spent in and the number of entries into open arms compared to the control group. Conclusion: The findings suggest that various concentrations of water-methanol extracts from Cannabis sativa exhibit sedative effects that are superior to those of the control (diazepam), supporting the use of this plant in traditional medicine. Further research should be conducted to investigate the active components of Cannabis sativa and understand the mechanism of its effects before proceeding to clinical trials.

Pharmacodynamic evaluation and network pharmacology analysis of a novel anti-heat stress Chinese herbal formula

Frequent extreme heat events around the world not only pose a major threat to human health but also cause significant economic losses to the livestock industry. The existing management practices are insufficient to fully prevent heat stress with an urgent need to develop preventive medicines. The aim of this study was to develop an anti-heat stress Chinese herbal formula (CHF) via big data analysis techniques and to evaluate its anti-heat stress effect and mechanism of action via pharmacodynamic evaluation and network pharmacology analysis. Many anti-heat stress CHFs were collected from the Chinese National Knowledge Infrastructure (CNKI) database. Three alternative CHFs were obtained via unsupervised entropy hierarchical clustering analysis, and the most effective CHF against heat stress, Shidi Jieshu decoction (SJD), was obtained by screening in a mouse heat stress model. In dry and hot environments, SJD significantly improved the heat tolerance of AA broilers by 4–6°C. In a humid and hot environment, pretreatment with 2% SJD resulted in 100% survival of Wenchang chickens at high temperatures. The main active ingredients of SJD were identified as muntjacoside E, timosaponin C, macrostemonoside H and mangiferin via ultra-performance liquid chromatography/mass spectrometry (UPLC/MS) and database comparison. The active ingredients of SJD were found to target tumor necrosis factor-α (TNF-α), signal transducer activator of transcription 3 (STAT3) and epidermal growth factor receptor (EGFR). Finally, the safety of the new formulation was assessed in an acute oral toxicity study in rats. The SJDs developed in this study provide a new option for the prevention of heat stress in animal husbandry and offer new insights for further research on anti-heat stress.

Cell Painting and Chemical Structure Read-Across Can Complement Each Other for Rat Acute Oral Toxicity Prediction in Chemical Early Derisking

Cell Painting and Chemical Structure Read-Across Can Complement Each Other for Rat Acute Oral Toxicity Prediction in Chemical Early Derisking

Computer prediction of acute toxicity of thioderivatives of 3,5-bis(5-mercapto-4-R-4H-1,2,4-triazol-3-yl)phenol

This study presents the computational prediction of acute toxicity for new derivatives of 3,5-bis(5-mercapto-4-R-4H-1,2,4-triazol-3-yl)phenols and their alkylated analogues. The aim of the work was to evaluate the impact of structural changes, particularly alkylation and chain length extension, on the toxicity levels of new derivatives of 3,5-bis(5-mercapto-4-R-4H-1,2,4-triazol-3-yl)phenols and their alkylated analogues. Materials and methods. QSAR methodologies were used to predict toxicity, allowing the evaluation of toxicological properties based on molecular descriptors. Toxicity modeling was performed using computer software, enabling the estimation of toxicity without the need for in vivo experimental studies. Results. The results showed, that alkylation of 3,5-bis(5-mercapto-4-R-4H-1,2,4-triazol-3-yl)phenol derivatives does not lead to a significant toxicity reduction. Moreover, an increase in toxicity was observed with the prolongation of the carbon chain in the synthesized compounds. It was also found, that acid derivatives, particularly 2,2’-(((5-hydroxy-1,3-phenylene)bis(4-R-4H-1,2,4-triazol-5,3-diyl))bis(sulfanyl))diacetate acids and 3,3’-((((5-hydroxy-1,3-phenylene)bis(4-R-4H-1,2,4-triazol-5,3-diyl))bis(sulfanyl))bis(methylene))dibenzoyl acids, exhibit toxicity ranging from 521.9 mg/kg to 2232.2 mg/kg, corresponding to toxicity class IV (low toxicity) on the OECD scale. It was found, that molecular structure and hydrophobic properties play a crucial role in determining compound toxicity. This study helps to establish a structure-toxicity relationship and to optimize compound structures for reduced toxicity. Conclusions. These results provide a foundation for further development of potential drug candidates with predicted toxicological properties.

Computer prediction of toxicity of new S-alkyl derivatives of 1,2,4-triazole

1,2,4-Triazole derivatives are of researchers’ significant interest due to their diverse biological properties, such as antimicrobial, anti-inflammatory, anticancer, and antioxidant activities. The integration of a 2-bromo-4-fluorophenyl fragment into the triazole structure can significantly enhance these activities. However, the evaluation of the toxicity of such compounds remains a critically important aspect for their practical application. To reduce the time and cost of experimental studies, QSAR (Quantitative Structure-Activity Relationship) methods are actively used, allowing the prediction of toxicity based on the molecular structure of compounds. Aim of the study. To assess the toxicity of new S-derivatives of 5-(2-bromo-4-fluorophenyl)-4-R-1,2,4-triazol-3-thiols using the QSAR method, specifically to predict acute toxicity parameters (LD50), and to determine the influence of different (length) radicals on the toxicity of these compounds. Materials and methods. The objects of the virtual study were derivatives of 5-(2-bromo-4-fluorophenyl)-4-ethyl-1,2,4-triazol-3-thiols. They were evaluated at the Department of Toxicological and Inorganic Chemistry of the Zaporizhzhia State Medical and Pharmaceutical University. The toxicity assessment was conducted using the nearest neighbor method via the Toxicity Estimation Software Tool (TEST). The prediction of the lethal dose (LD50) for rats was based on the structural similarity of the studied compounds with known substances, for which experimental toxicity data are available. Results. The conducted QSAR analysis demonstrated that structural changes in S-derivatives of 5-(2-bromo-4-fluorophenyl)-4-ethyl-1,2,4-triazol-3-thiols significantly affect the predicted toxicity. The primary factor influencing the changes in LD50 values is the variation of radicals at the 5th position of the triazole ring. Conclusions. The results of the study showed, that the toxicity of new S-alkyl derivatives of triazol-3-thiols depends on the type of alkyl substituent. Compounds with propyl to heptyl fragments exhibit increased toxicity, while derivatives with thiol, octyl, nonyl, and decyl residues are characterized by lower toxicity.

QSAR prediction of toxicity for a new 1,2,4-triazole derivatives with 2-bromo-5-methoxyphenyl fragment

New derivatives of 1,2,4-triazole are promising research targets due to their unique biological properties, including antimicrobial, antifungal, antitumor, and antioxidant activities. The introduction of the 2-bromo-5-methoxyphenyl fragment into the triazole structure potentially enhances these properties. However, the issue of toxicity for such compounds remains a critical factor for their further application. To reduce experimental costs and time, QSAR (Quantitative Structure-Activity Relationship) methods are widely applied, allowing to predict compounds toxicity based on their molecular structure. The aim of this study was to evaluate the toxicity of new derivatives of 5-(2-bromo-5-methoxyphenyl)-4-R-1,2,4-triazole-3-thiols, their acids, and esters using the QSAR method to predict parameters of acute toxicity (LD50) and to assess the influence of various radicals on the toxicity of the compounds. Materials and methods. The objects of this study were derivatives of 5-(2-bromo-5-methoxyphenyl)-4-R-1,2,4-triazole-3-thiols, synthesized at the Department of Toxicological and Inorganic Chemistry of Zaporizhzhia State Medical and Pharmaceutical University. The nearest neighbor method was used for toxicity evaluation, applying the Toxicity Estimation Software Tool (TEST). The prediction of rats lethal dose (LD50) was based on the structural similarity of the studied compounds with known substances that have experimental toxicity data. Results. The QSAR analysis revealed that structural modifications in the derivatives of 5-(2-bromo-5-methoxyphenyl)-4-R-1,2,4-triazole-3-thiols significantly influence their toxicity. Specifically, increasing the size of the radicals, especially through the introduction of aromatic fragments, contributed to the enhanced safety of the compounds, as evidenced by the increase in LD50 values. The highest LD50 values were observed for compounds containing phenyl radicals. Conclusions. The results of this study indicate the feasibility of using QSAR models to predict the toxicity of 1,2,4-triazole derivatives containing a 2-bromo-5-methoxyphenyl fragment. The observed trend of increasing safety with the introduction of larger aromatic radicals can be used for the rational design of new compounds with improved toxicological properties.

Research on the pharmacological potential of 1-alkyl derivatives of 3,5-dimethyl-4-((4-nitrobenzylidene)amino)-1,2,4-triazolium bromide

The heterocyclic system of 1,2,4-triazole and its derivatives is one of the leaders in the development of highly promising biologically active compounds. The peculiarities of the chemical structure of the derivatives of this heterocycle provide a wide range of possibilities for chemical transformations that allow to obtain really effective drugs. The involvement of several substituents in chemical transformations simultaneously, which have the properties of highly reactive centers, additionally creates favorable conditions for the formation of rational ways to create a biologically active compound. Amino-, mercapto- or hydroxogroups often play the role of such groups in chemistry. The use of these groups as substituents of 1,2,4-triazole synthon provides multifaceted opportunities for directed chemical transformation. The ability of such structural fragments to form chemical interactions and bonds with biological targets has an additional positive effect in the sense of their involvement in chemical transformations on the way to the targeted production of a biologically active substance. Thus, the combination of a heterocyclic structure with a highly reactive chemical center is endowed with theoretically sound and practically significant meaning. The aim of the work is to preliminary determine the potential for creating a biologically active substance with antifungal action based on 1-alkyl derivatives of 3,5-dimethy-l-4-((4-nitrobenzylidene)amino)-1,2,4-triazolium bromide. Materials and methods. The toxicity of the studied compounds has been predicted using the TEST program (Toxicity Estimation Software Tool), which allowed to determine the predictive level of acute toxicity, ecotoxicity and mutagenicity. The physicochemical and pharmacokinetic parameters have been predicted, and the drug-like properties and availability of the investigated substances have been assessed using the online resource SwissADME. The determination of the most favorable spatial configuration of the ligand relative to the active site of the protein and the assessment of the strength of their interaction have been realized using the computational method of molecular docking. The ligands have been prepared using MarvinSketch 6.3.0, HyperChem 8 and AutoDock Tools-1.5.6 software. The preparation of the model enzyme has been based on the use of Discovery Studio 4.0 and AutoDock Tools-1.5.6. The practical implementation of flexible molecular docking has been carried out using the software tools of the AutoDock/Vina platform. Results. In the process of step-by-step prescreening of the formed structures of a number of 1-alkyl derivatives of 3,5-dimethyl-4-((4-nitrobenzylidene)amino)-1,2,4-triazolium bromide, a number of qualitative and quantitative indicators related to the physicochemical characteristics and pharmacokinetic parameters of the studied substances have been obtained. According to the results of the first stage of research, the group of substances under consideration can be predictively considered low-toxic, but with a high risk of mutagenic properties. The next stage of the work, which involved the analysis of physicochemical parameters, pharmacokinetic parameters, general drug-like properties and bioavailability, allowed us to identify 1-alkyl derivatives of 3,5-dimethyl-4-((4-nitrobenzylidene)amino)-1,2,4-triazolium bromide as substances with a rather positive pharmacological profile. The final stage in the form of molecular docking of the structure of the studied compounds to the active site of lanosterol 14α-demethylase allowed us to determine the nature of the chemical interaction and the type of amino acid residues that may be involved in the antifungal properties of the key ligands. The analysis of the docking results allows us to determine the privileged nature of the nonyl substituent at the first Nitrogen atom of the 1,2,4-triazole synthon in the structure of the presented series of compounds for the formation of antifungal properties. Conclusions. The general prospects for the creation of a biologically active substance with antifungal properties using 1-alkyl derivatives of 3,5-dimethyl-4-((4-nitrobenzylidene)amino)-1,2,4-triazolium bromide look quite realistic. Particular attention should be paid to 3,5-dimethyl-1-nonyl-4-((4-nitrobenzylidene)amino)-1,2,4-triazolium bromide as a substance with significant potential for antifungal properties, which allows us to recommend this compound for further more constructive and extended in vitro and in vivo studies.

Acute Oral Toxicity Assessment of Repchol in Wistar Rats: A Liver-protective Herbal Premix for Poultry

The present study was conducted for the assessment of acute oral toxicity and safety analysis of Repchol Premix (M/s Ayurvet Limited) according to OECD-423 guidelines. Six adult Wistar rats, weighing 113-134 g, were used for the study. After oral administration of Repchol@ 300 and 2000mg/kg body weight, the animals were observed for manifestation of toxic effect and death upto14 days. Evaluation of safety analysis and toxicity was assessed on the basis of presence of mortality or toxicity symptoms. Every animal in group served as its own control. At the end of experiment blood biochemical parameters and histopathological changes in heart, liver, kidney and lung were studied. The results showed that Repchol did not produce toxic effects or mortality during the experimental period. The body weight changes observed for two weeks were in the normal range. In Repchol treated rats biochemical parameters like AST, ALT, ALP and creatinine were observed within normal range and in histopathological examination no significant microscopic alterations were observed. Thus, the observations indicated that Repchol Premix did not produce toxic effect or acute oral toxicity and the LD50 of compound is beyond 2000mg/kg.

Automated acute skin toxicity scoring in a mouse model through deep learning.

This study presents a novel approach to skin toxicity assessment in preclinical radiotherapy trials through an advanced imaging setup and deep learning. Skin reactions, commonly associated with undesirable side effects in radiotherapy, were meticulously evaluated in 160 mice across four studies. A comprehensive dataset containing 7542 images was derived from proton/electron trials with matched manual scoring of the acute toxicity on the right hind leg, which was the target area irradiated in the trials. This dataset was the foundation for the subsequent model training. The two-step deep learning framework incorporated an object detection model for hind leg detection and a classification model for toxicity classification. An observer study involving five experts and the deep learning model, was conducted to analyze the retrospective capabilities and inter-observer variations. The results revealed that the hind leg object detection model exhibited a robust performance, achieving an accuracy of almost 99%. Subsequently, the classification model demonstrated an overall accuracy of about 85%, revealing nuanced challenges in specific toxicity grades. The observer study highlighted high inter-observer agreement and showcased the model's superiority in accuracy and misclassification distance. In conclusion, this study signifies an advancement in objective and reproducible skin toxicity assessment. The imaging and deep learning system not only allows for retrospective toxicity scoring, but also presents a potential for minimizing inter-observer variation and evaluation times, addressing critical gaps in manual scoring methodologies. Future recommendations include refining the system through an expanded training dataset, paving the way for its deployment in preclinical research and radiotherapy trials.

Molecular docking and molecular dynamics of hypoxia-inducible factor (HIF-1alpha): towards potential inhibitors

HIF-1α is a primary regulator in the adaptation of cancer cells to hypoxia. The aim was to find out new inhibitors of the HIF-1α. A molecular dynamic (MD) simulation performed on HIF-1α showed stable dynamic features. Virtual screening of 217 anticancer drugs was performed along with a positive control (2-Methoxyestradiolm, 2-ME2) on an optimized HIF-1α and dynamically simulated structure. Docking results produced two compounds namely pycnidione and nilotinib of high binding affinity −9.34 kcal/mol and −9.04 kcal/mol respectively, whereas 2-ME2 displayed a relatively lower affinity (-6.68 kcal/mol). For the three complexes, MD of 200 ns simulation was run. Data analysis showed that the three medications behaved similarly in the MD simulation. Nilotinib had a lower RMSD and higher SASA than the other complexes. In addition, the Nilotinib-HIF-1α combination had a lower RMSF value, a flatter Rg, and a number of hydrogen bonds similar to other complexes. MM-GBSA analysis revealed that nilotinib, pycnidione and 2-ME2 compounds had free binding energy of −23.77 ± 5.29, −21.85 ± 4.24 and −7.53 ± 6.62 kcal/mol respectively. Nilotinib and pycnidione bind competitively to HIF-1α, with nilotinib showing consistent molecular-dynamic properties. They relatively pass the blood-brain barrier, non-carcinogenic, and have IV-category acute oral toxicity. They have low CYP inhibitory characteristics. Further investigations are therefore warranted to elucidate their implications in hypoxia pathways, cell proliferation, apoptosis, survival, and metastatic potential.

Polarized electric field-mediated graphitic carbon nitride-based S-scheme heterostructure for efficient photocatalytic removal of bisphenol A

Tuning interface charge transfer is considered as a feasible way to promote electron migration and separation in heterojunction system, but the role of in-plane electron behavior in single phase has received little attention. Here, a carboxyl functionalized graphitic carbon nitride (CCN) coupled PbBiO2Br (PBOB) S-scheme heterostructure is elaborately designed for investigation. Compared with pristine CN/PBOB, although the existence of carboxyl group weakens the built-in electric field strength of CCN/PBOB (ΔΦ = 0.44 eV), the formed polarized electric field (µ = 3.18 Debye) is conducive to the pre-separation of photogenerated electrons and holes in CCN, thereby improving interface charge transfer. In addition, the introduced carboxyl group can also serve as an O2 adsorption site to enhance its activation, and generate reactive oxygen species (ROS) through a two-step single-electron O2 reduction route. Thus, the optimized CCN/PBOB exhibits excellent photocatalytic ROS generation ability, which can remove 88.7 % of bisphenol A and significantly reduce the acute toxicity of the formed intermediates. This work provides a new perspective for the development of advanced heterojunction photocatalyst by regulating in-plane/interface charge dynamics, and helps to fully understand the pollutant detoxification/degradation process initiated by molecular oxygen activation.

Is environmental risk assessment possible with the alternatives to acute fish toxicity test? Case study with pharmaceuticals

BackgroundAcute fish toxicity test (AFT) is one of the cornerstones of environmental risk assessment (ERA) of chemicals for the aquatic environment. Despite many efforts to find an alternative able to fully replace the test, there is still lasting pressure from stakeholders for AFT results. ResultsHere, we present the results of a case study with eight pharmaceuticals from various pharmaceutical groups with different levels of expected toxicity to fish. Selected compounds were tested in two validated alternative tests—fish embryo toxicity test with zebrafish (Danio rerio) (zFET) and in vitro RTgill-W1 assay according to their corresponding OECD guidelines TG 236 and TG 249, respectively. Data for AFT were collected from PubMed and ECOTOX knowledgebase databases, and acute toxicity to fish was further predicted in silico by the ECOSAR program. Predicted environmental risks (risk quotients, RQ, calculated using the exposure data from NORMAN) from both zFET and RTgill-W1 well correlated with the average RQs based on AFT LC50s. The strongest and most significant correlation was observed while comparing the AFT results with the median of combined alternative methods (zFET, RTgill-W1, ECOSAR).ConclusionsThis proposed approach combining experimental data with modeling could serve as a reliable tool for predictions of environmental risks promoting the 3R alternatives to acute fish toxicity testing.

Once-a-Week Ablative Radiotherapy as Replacement of Prolonged Fractionation in Frail Patients: Feasibility and Toxicity Results

Introduction The aim of this work was to explore the use of an original once-weekly radiotherapy fractionation in elderly or frail patients with recurrence or metastasis from different solid malignancies. Material and Methods A retrospective analysis was conducted on 29 patients treated from 2011 to 2019 with a once-weekly radiotherapy schedule. Patients received a median dose of 27.5 Gy, with weekly fractions of 4-5 Gy over 7-10 weeks. The treatment aimed at both palliative and cytoreductive objectives. Primary endpoints were feasibility and compliance, secondary outcome was acute toxicity. Results All patients completed the planned radiotherapy without interruptions. Acute toxicity was mild, with only one patient developing grade 3 toxicity (bowel perforation). Three months post-treatment, 74% of patients experienced symptom relief and tumor response. One-year local control rates were 26.7%, and treatment was generally well-tolerated. Conclusion This once-weekly hypofractionated radiotherapy regimen demonstrated feasibility, good tolerance, and promising tumor response in frail and elderly patients. Although limited by a small sample size, the approach offers a practical alternative for patients unable to undergo conventional daily radiotherapy. Further studies on larger cohorts are required to validate these findings.

Cardiovascular Disease in Acute Cocaine Compared to Acute Fentanyl Intoxication Deaths.

Cocaine is the most common stimulant drug that causes death in Connecticut. Unlike opioid intoxication deaths, which largely correlate with dose/concentration, cocaine deaths occur more idiosyncratically, with mechanisms of death often related to underlying cardiovascular disease. We examined 78 sole acute cocaine and 306 sole acute fentanyl intoxication deaths to assess their association with cardiovascular disease. In the cocaine cohort, 87% (68/78) had atherosclerotic and/or hypertensive cardiovascular disease while 40% (122/306) in the fentanyl cohort did. Cocaine was detected in 40% of all accidental drug intoxication deaths, 41% of all accidental drug intoxication deaths involving fentanyl, and 37% of all drug intoxication deaths involving heroin. The relatively low number of sole cocaine deaths compared to the much higher proportion of cocaine/opioid deaths may be explained by the synergistic effects encountered in many mixed drug intoxications, the contributory role of cardiovascular disease in sole cocaine deaths, and/or the increased prevalence and potency of fentanyl. The high number of sole cocaine deaths in which the decedents had co-existing heart disease compared to those from sole fentanyl deaths (P < 0.001) suggests that heart disease plays a mechanistic role in sole cocaine deaths, whereas the potency of fentanyl is the dominant mechanism in fentanyl deaths.

Synergistic effect of curcumin and Piperine loaded Niosomal nanoparticles on acute pulmonary toxicity induced by Paraquat in mice.

Paraquat (PQ), a widely used non-selective herbicide, induces severe lung toxicity by promoting cell death and tissue necrosis through the generation of reactive oxygen species (ROS) and free radicals. This study aimed to develop and evaluate novel niosomal nanoparticles (NPs) encapsulating curcumin and piperine to mitigate PQ-induced acute pulmonary toxicity in Balb/c mice. The NPs were prepared using non-ionic surfactants and cholesterol via the thin film hydration method. Characterization revealed high encapsulation efficiency (>85%), proper particle sizes (264-286nm), narrow polydispersity index (PDI) (0.19±0.04 to 0.23±0.02), and good stability over 90days. Thermal analysis confirmed successful encapsulation of curcumin and piperine within the niosomal NPs. In vivo studies showed that PQ exposure significantly elevated ROS, lipid peroxidation (LPO), and protein carbonylation (PC) levels, while reducing glutathione (GSH) levels and impairing mitochondrial function (P<0.001). However, co-treatment with curcumin- and piperine-loaded niosomal NPs effectively reversed these effects (P<0.001), improving mitochondrial function. The combined formulation of curcumin and piperine in niosomal NPs offers a promising therapeutic strategy for treating PQ-induced pulmonary toxicity, likely due to enhanced bioavailability and potent antioxidant activity.

Efficacy and safety assessment of probiotic Bacillus coagulans (Heyndrickxia coagulans) BCP92 for treatment of diarrhea

Abstract Objective: Probiotics offer a potentially new therapeutic approach for the treatment of diarrhea. This study aimed to determine the anti-diarrheal activity of Bacillus coagulans BCP92 (MTCC 25460) and its safety assessment (acute and sub-acute toxicity studies) in animal models and cell lines. Methods: The antidiarrheal activity was studied in mice using a castor oil-induced diarrhea model. In the acute toxicity study, the rats were orally fed 2000 mg/kg (4 × 1011 CFU/g) of B. coagulans BCP92 (MTCC 25460) as a single dose, and for sub-acute toxicity study rats received 250, 500, and 1,000 mg/kg/day for 28 days. At the end of the treatment, body weight, organ weight, food intake, biochemical parameters, hematological parameters, and histopathology were studied. B. coagulans BCP92 is effective against diarrhea by reducing the onset of diarrhea (latency), frequency of defecation, total fecal weight, and percentage of defecation. In-vitro MTT assay was performed on Vero cell lines. Results: In-vitro MTT assay showed a cytoprotective effect. In acute toxicity study, 2000 mg/kg dose did not cause any alteration in clinical signs, morbidity, or mortality. The findings of the subacute toxicity study showed no alterations in physical appearance and behavioral patterns. Moreover, no significant variations were found in organ weights and hematological and biochemical parameters of the treated groups in the control group. Furthermore, no visible histological changes were observed in the heart, lung, liver, and kidney of the high-dose treatment groups. Conclusion: Thus, the results of the present study conclude that B. coagulans BCP92 is safe for human use in the treatment of diarrhea.

Assessment of unintentional acute pesticide poisoning among smallholder vegetable farmers in Trinidad and Jamaica

Poisoning caused by pesticides is widely recognized as a major public health problem among smallholder farmers and rural communities, including in the Caribbean. However, a lack of quality data impedes understanding of the problem and hampers the development of effective strategies for its management. To better understand the prevalence of unintentional acute pesticide poisoning (UAPP) in Trinidad and Tobago and Jamaica and the pesticides and practices involved, we conducted a cross-sectional survey of 197 and 330 vegetable farmers in Trinidad and Jamaica, respectively. The findings from this study revealed a high incidence of self-reported health effects from occupational pesticide exposure, with 48 and 16% of respondents, respectively, experiencing symptoms of UAPP within the previous 12 months. Furthermore, the substantial proportion of UAPP incidents were associated with a few highly hazardous pesticides (HHPs), particularly lambda-cyhalothrin, acetamiprid, and profenofos in Jamaica, and alpha-cypermethrin, paraquat and lambda-cyhalothrin in Trinidad. Given the well-documented adverse effects of these chemicals on human health, the results of this study should be of significant concern to health authorities in Jamaica and Trinidad. This clearly indicates an urgent need for improved regulation and safer alternatives to the use of HHPs, as well as the promotion of alternatives. We provide policy recommendations and identify alternatives to HHPs for tropical vegetable production.

The Effects of Seed Inoculation with Bacterial Biofilm on the Growth and Elemental Composition of Tomato (Solanum lycopersicum L.) Cultivated on a Zinc-Contaminated Substrate

Biofilm obtained from Bacillus subtilis subsp. spizizenii inoculated on vegetable seeds has been shown to have plant growth-promoting capacity. Seed inoculation with biofilm produced by this strain could also reduce the adverse effects on plant growth caused by soil or substrate heavy metal overabundance. Therefore, the objective of this work was to evaluate the impact of biofilm inoculated on tomato (Solanum lycopersicum L.) seeds, which were planted on a substrate with artificially added zinc. First, seeds of the Río Grande tomato variety were exposed to increasing zinc concentrations, namely: 50, 100, 200, and 400 ppm, with and without bacterial biofilm inoculation. Zinc addition and seed inoculation affected germination parameters. For example, an extra 200 and 400 ppm of zinc led to high toxicity. Biofilm inoculation, however, reduced the noxious effects of excess zinc, bringing acute toxicity down to moderate. Then, tomato plants growing from inoculated and non-inoculated seeds were cropped for 4 months in both substrates with 400 ppm zinc and without added zinc. Extra zinc addition significantly (p &lt; 0.05) reduced tomato root and shoot biomass, plant height, and fruit number at harvest time. However, seed biofilm inoculation avoided the harmful effect of zinc on plant growth parameters, fruit yield, and fruit quality. The roots and shoots of plants growing on contaminated substrates showed very noticeable increases in zinc levels compared to the control, while fruits only showed a much weaker zinc gain, even if this was significant (p &lt; 0.05). Moreover, root shoot and fruit concentrations of elements other than zinc, (nitrogen, phosphorus, potassium, calcium, magnesium, sulfur, iron, manganese, copper, lead, and cadmium) were not or only weakly affected by the addition of this metal to the substrate. In summary, the biofilm of B. subtilis proved to be effective as a bioinoculant to alleviate negative effects on tomatoes cropped in a substrate with excess zinc.

Are Biobased Microfibers Less Harmful than Conventional Plastic Microfibers: Evidence from Earthworms.

Biobased plastics are sometimes promoted as "environmentally friendly" compared to their conventional petrochemical-based counterparts, but their ecotoxicity is only partially understood. Biobased fibers are widely used in clothing and wet wipes and can accumulate in soils through the application of biosolid fertilizers. This study examined the lethal thresholds and sublethal toxicity of chemically characterized, additive-free, biobased (viscose and lyocell) compared to petrochemical-based (polyester) fibers on the key ecosystem engineer, Esenia fetida. Viscose and lyocell had LC20 values of 14.00 and 22.66 mg·L-1, respectively, and no observed effect concentrations (NOEC) of 0-2.8 mg·L-1 (72 h, OECD TG207 filter paper method), while for polyester these were LC20 15.6-31.3 mg·L-1 and NOEC 0-15.6 mg·L-1. Following 28 days of exposure to soils (OECD TG222) contaminated with environmentally relevant concentrations (100 mg kg-1), viscose significantly reduced the mass of progeny compared to polyester. Earthworms exposed to lyocell had a marginal growth reduction (-18%; compared to -11% to -13% in other treatments) linked to increased bioturbation activity. The biobased fibers examined here have greater acute toxicity at high concentrations and broadly similar sublethal effects on E. fetida compared to polyester. Our study highlights the importance of detailed testing before advocating specific materials as plastic alternatives/substitutes to conventional plastics.