Poisoning Research Articles

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.

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. 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. 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. Thus, the results of the present study conclude that B. coagulans BCP92 is safe for human use in the treatment of diarrhea.

Clinical Implementation of Cone Beam Computed Tomography-Guided Online Adaptive Radiation Therapy in Whole Breast Irradiation

PurposeIn postoperative breast irradiation, changes in the breast contour and arm positioning can result in patient positioning errors and offline re-planning. This can lead to increased treatment burden, and strain on departmental logistics due to the need for additional cone-beam CT images or even a new radiotherapy treatment plan (TP). Online daily adaptive radiotherapy (oART) could provide a solution to these challenges. We have clinically implemented and evaluated the feasibility of oART for whole breast irradiation. Methods and MaterialsTwenty patients treated with postoperative whole breast right irradiation (5 × 5.2 Gy) were included in BREAST-ART, a prospective single-arm trial. Dosimetry of the reference TP calculated on the daily anatomy and adaptive TP were compared. Duration of the oART workflow, in-house satisfaction questionnaires, and acute toxicity (CTCAE v5.0) was collected. The oART workflow was evaluated by investigating the impact of manual corrections of influencer and target contours on treatment time and quality. ResultsIn the first 17 patients (85 fractions), the on-couch time, i.e. time between the end of CBCT1 and CBCT3, was median 13.8 minutes (range=11–25). Retrospective evaluation of the use of the influencer (i.e. breast) in 4 patients (20 fractions) and manual correction of the most cranial and caudal target contours (i.e. 4 mm) in 10 patients (36 fractions) was done. This resulted in a reduced on-couch time in the last 3 clinical patients to a median of 13.0 minutes (range=11–19). No grade 3 or higher toxicity was observed, and 19/20 patients indicated to prefer the same treatment again. Skin marks for patient positioning during treatment were no longer necessary. ConclusionsThis study showed the feasibility, challenges, and practical solutions for the implementation of oART for breast cancer patients. Future work will focus on more complex breast indications such as whole breast including axillary nodes, to further investigate benefits and challenges of oART in breast cancer.

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 < 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 < 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.

Expanding the Solvent/Protein Region Occupation of the Non-Nucleoside Reverse Transcriptase Inhibitor Binding Pocket for Improved Broad-Spectrum Anti-HIV-1 Efficacy: from Rigid Phenyl-Diarylpyrimidines to Flexible Hydrophilic Piperidine-Diarylpyrimidines.

Considering the nonideal antiresistance efficacy of our previously reported non-nucleoside reverse transcriptase inhibitor 7, a series of novel piperidine-diarylpyrimidine derivatives were designed through expanding solvent/protein region occupation. The representative compound 15f proved to be exceptionally potent against Y188L (EC50 = 23 nM), F227L + V106A (EC50 = 15 nM) and RES056 (EC50 = 45 nM), significantly better than 7. This analog exerted strong inhibition against wild-type HIV-1 (EC50 = 3 nM) and single mutant strains (L100I, K103N, Y181C, E138 K). Notably, its cytotoxicity and selectivity (CC50 = 18.23 μM, SI = 6537) were 4-fold better than etravirine and rilpivirine. Additionally, it exhibited minimal suppression of CYP isoenzymes and hERG, indicating low potential for drug-drug interactions and cardiotoxicity. No significant acute toxicity and tissue damage at a dose of 2 g/kg were revealed. These findings lay the groundwork for the advancement of 15f as a highly potent, safe, and broad-spectrum NNRTI for HIV therapy.

Lung stereotactic radiation therapy: Early results from the Salah Azaiez Institute.

Stereotactic Body Radiation Therapy (SBRT) has transformed lung cancer care, delivering precise treatment with minimal harm to healthy tissue. This study examined the experience at the Salah Azaiez Institute (SAI) in lung cancer patients. we conducted a retrospective study on patients treated with SBRT from 2019 to 2022. Planification imaging included four-dimensional CT scans and delineation of target volumes and organs-at-risk was done as per international guidelines. Treatment doses were tailored based on tumour location. A total of 10 cases were included. The male-to-female sex ratio was 4:1, with a median age of 69.5 years. Three had unconfirmed primary lung tumours, while five had inoperable stage I-IIA adenocarcinomas primarily due to compromised respiratory function. Two had oligometastatic lung diseases. All underwent recent thoracic-CT and PET-CT evaluations to exclude pulmonary fibrosis. The median lesion size was 40mm. Karnofsky's performance status ranged from 70 to 90, with no contraindications to the supine position. Eight out of 10 patients received 8 fractions of 7.5 Gy at the 80% isodose. For that regimen, the D95%, D99%, and Dmax were respectively, 60 Gy, 56 Gy, 73 Gy. All organs-at-risk dosimetric criteria were met. Acute toxicities included worsened coughs in 2 patients and fatigue in 6. After a mean follow-up of 23 months, no rib fractures or haemoptysis were observed, and no local recurrence was reported on the last chest CT scan. SBRT demonstrates promise for lung cancer treatment, though challenges persist in precise targeting and motion management. Effective multidisciplinary collaboration and local protocols are crucial for successful implementation.

Embryonic exposure to glycopeptides induces acute toxicity and developmental neurotoxicity in zebrafish (Danio rerio)

Glycopeptide antibiotics are crucial in combating severe bacterial infections. However, concerns persist regarding their environmental impact and potential toxicity to human health. This study explores the dose-dependent toxicity of glycopeptide antibiotics on zebrafish embryos, revealing significant differences in developmental and neurological effects. Our findings indicate that oritavancin (ORI) and telavancin (TEL) exhibit greater acute toxicity compared to vancomycin (VAN). High doses of glycopeptides cause notable developmental abnormalities, including reduced body length and potential organ formation disruptions. TEL’s prominent accumulation in embryos likely contributes to its heightened toxicity. The study also highlights differential effects on zebrafish locomotion, with ORI affecting sensory processing and motor control, TEL altering swimming time distribution, and VAN influencing inactivity and active swimming, varying by concentration and light-dark cycles. Molecular analyses, including RNA-seq and qRT-PCR, show that glycopeptides significantly alter gene expression related to nervous system development, particularly affecting sipa1l1, a gene essential for synaptic function and dendritic spine growth. The disruption of neurodevelopmental pathways suggests mechanisms through which these compounds influence development. These findings underscore the critical role of glycopeptide structure in toxicity and emphasize the need for further research to delineate specific affected molecular pathways, which could guide future studies and treatments for neurodevelopmental disorders.

Shifts in the spatiotemporal profile of inflammatory phenotypes of innate immune cells in the rat brain following acute intoxication with the organophosphate diisopropylfluorophosphate

Acute intoxication with cholinesterase inhibiting organophosphates (OP) can produce life-threatening cholinergic crisis and status epilepticus (SE). Survivors often develop long-term neurological consequences, including spontaneous recurrent seizures (SRS) and impaired cognition. Numerous studies implicate OP-induced neuroinflammation as a pathogenic mechanism contributing to these chronic sequelae; however, little is known about the inflammatory phenotype of innate immune cells in the brain following acute OP intoxication. Thus, the aim of this study was to characterize the natural history of microglial and astrocytic inflammatory phenotypes following acute intoxication with the OP, diisopropylfluorophosphate (DFP). Adult male and female Sprague–Dawley rats were administered a single dose of DFP (4 mg/kg, sc) followed by standard medical countermeasures. Within minutes, animals developed benzodiazepine-resistant SE as determined by monitoring seizures using a modified Racine scale. At 1, 3, 7, 14, and 28 d post-exposure (DPE), neuroinflammation was assessed using translocator protein (TSPO) positron emission tomography (PET) and magnetic resonance imaging (MRI). In both sexes, we observed consistently elevated radiotracer uptake across all examined brain regions and time points. A separate group of animals was euthanized at these same time points to collect tissues for immunohistochemical analyses. Colocalization of IBA-1, a marker for microglia, with iNOS or Arg1 was used to identify pro- and anti-inflammatory microglia, respectively; colocalization of GFAP, a marker for astrocytes, with C3 or S100A10, pro- and anti-inflammatory astrocytes, respectively. We observed shifts in the inflammatory profiles of microglia and astrocyte populations during the first month post-intoxication, largely in hyperintense inflammatory lesions in the piriform cortex and amygdala regions. In these areas, iNOS+ proinflammatory microglial cell density peaked at 3 and 7 DPE, while anti-inflammatory Arg1+ microglia cell density peaked at 14 DPE. Pro- and anti-inflammatory astrocytes emerged within 7 DPE, and roughly equal ratios of C3+ pro-inflammatory and S100A10+ anti-inflammatory astrocytes persisted at 28 DPE. In summary, microglia and astrocytes adopted mixed inflammatory phenotypes post-OP intoxication, which evolved over one month post exposure. These activated cell populations were most prominent in the piriform and amygdala areas and were more abundant in males compared to females. The temporal relationship between microglial and astrocytic responses suggests that initial microglial activity may influence delayed, persistent astrocytic responses. Further, our findings identify putative windows for inhibition of OP-induced neuroinflammatory responses in both sexes to evaluate the therapeutic benefit of anti-inflammation in this context.

Toxicity of the microencapsulated extract of seeds of Annona muricata L. (Annonaceae) on Africanized honey bees

Pesticide toxicity is one of the causes of pollinator decline worldwide. Here we evaluate the chronic (for seven days) and acute (for one day) toxicity of a microencapsulated formulation (MF) obtained from Annona muricata seeds on Apis mellifera in concentrations of 0.157 and 2.49 g. When bees were exposed daily to the formulation, a small increase in mortality occurred, and a significant difference was observed (p < 0.001) between t survival curves. During the acute toxicity exposure, there was a low mortality in the first days after exposure. Based on the results obtained, we assume that the MF has low acute toxicity and chronic using LC50 on A. mellifera.

Comprehensive genomic analysis and evaluation of in vivo and in vitro safety of Heyndrickxia coagulans BC99

This study aimed to evaluate the safety profile and beneficial effects of Heyndrickxia coagulans strain BC99 (BC99) for potential use in functional foods and pharmaceuticals. We began with whole genome sequencing of BC99, followed by a comprehensive safety assessment comprising genome analysis, hemolysis, cytotoxicity, antibiotic susceptibility tests, and cell adhesion and tolerance studies, along with acute and subacute oral toxicity studies in animal models. BC99 was isolated from a well-characterized collection originating from the feces of a healthy infant. Our results indicated no hemolytic activity on Columbia blood agar plates and broad antibiotic sensitivity, including to gentamicin, ampicillin, chloramphenicol, ciprofloxacin, and others. Cytotoxicity testing confirmed no adverse effects on HT-29 cells and significant adhesive properties to intestinal epithelial cells. Tolerance tests demonstrated over 90% viability of BC99 under simulated gastrointestinal conditions. In vivo studies in mice and rats confirmed the absence of adverse effects following oral administration. Collectively, these findings support BC99’s robust tolerance to gastrointestinal environments, strong adhesion capabilities, and a broad spectrum of antibiotic resistance, underlining its potential as a safe and effective agent for gut microbiota modulation and host health enhancement.

Chitosan nanoparticles of imatinib mesylate coated with TPGS for the treatment of colon cancer: In-vivo & in-vitro studies

The study aimed to develop and evaluate chitosan-based nanoparticles coated with TPGS for the targeted delivery of imatinib mesylate to colon cancer cells. Particle size and zeta potential analysis were within the acceptable range for targeting colon cancer. CS-IMT-TPGS-NPs had a significant positive zeta potential of 30.4 mV, suggesting improved cellular intake. FE-SEM and TEM demonstrated that the nanoparticles appeared spherical, smooth, and did not aggregate, with a visible TPGS coating. XRD confirmed that crystalline imatinib transitioned to an amorphous state during nano formulation. In-vitro tests on HCT-116 cells demonstrated that CS-IMT-TPGS-NPs outperformed free IMT regarding cytotoxicity, apoptosis induction, cellular uptake, and cell migration inhibition. Additionally, the nanoparticles were examined in vitro using mitochondrial membrane potential, DNA fragmentation, GAPDH relative gene expression, ROS estimation, and cell cycle analysis. The effect of therapy on expected colon-associated bacterial strains was also investigated. The biocompatibility of nanoparticles was assessed by hemolysis and platelet aggregation experiments. The anti-inflammatory impact was determined using the HET-CAM test. Non-Fickian diffusion at pH 5.5 resulted in sustained in-vitro drug release, with no initial burst. In-vivo investigations using albino Wistar rats suggest pharmacokinetic properties for produced nanoparticles, whereas histopathological examinations assess acute toxicity.

Acute toxicity study and antibacterial activity of aqueous and methanol leaf extract of &lt;i&gt;Crotolaria retusa&lt;/i&gt; Linn. against multidrug resistant bacterial isolates

Acute toxicity study and antibacterial activity of aqueous and methanol leaf extract of &lt;i&gt;Crotolaria retusa&lt;/i&gt; Linn. against multidrug resistant bacterial isolates

The Acute Toxicity and Cardiotoxic Effects of Protocatechuic Aldehyde on Juvenile Zebrafish.

Protocatechuic aldehyde (PCA) is a natural phenolic acid compound with pharmacological effects such as anti-oxidative stress, antibacterial, anti-apoptotic, anti-inflammatory, anti-platelet aggregation, and anti-tumor. Despite the favorable therapeutic effects of PCA, it is imperative to recognize that adverse drug reactions can arise even with satisfactory quality assurance measures and during standard clinical application and dosing. Additionally, the acute toxicity and cardiotoxic sequelae of PCA are frequently under reported in the available documentation. To investigate the acute toxicity and cardiotoxic effects of PCA, the present study comprehensively assessed the acute toxicity and cardiotoxic effects of PCA by administering different concentrations of PCA and by monitoring the phenotypic changes in zebrafish, using AB wild-type Tg(cmlc2:EGFP) zebrafish as the experimental model organism. Meanwhile, the target genes of PCA that may cause cardiotoxicity were predicted and validated using a network pharmacology approach. Our findings indicated that PCA exhibited severe acute toxicity and cardiotoxic effects in zebrafish at 70 μg/mL and 80 μg/mL. Furthermore, PIK3CA, PARP1, and GSK3β may be involved in the mechanism of action of the cardiotoxicity-inducing effects of this compound. The present investigation has afforded a deeper insight into the acute toxicity and cardiotoxic impacts of PCA on zebrafish and has established a significant theoretical foundation for the evaluation of toxicity in pharmaceuticals incorporating PCA.

Managing Amitraz Poisoning: Epidemiological Data and Clinical Insights From a Tertiary Care Hospital in Southern India.

Background Amitraz is a formamidine insecticide and acaricide that acts on α2 adrenergic receptors. There is limited information in the literature regarding the toxicity of this compound and treatment of poisoning. Here, we have studied the epidemiology, symptoms, signs, complications, abnormalities in the tests, management, and prognosis of individuals who were admitted to a tertiary care hospital with acute amitraz intoxication. Methods This retrospective study was conducted at a tertiary care facility, Shri B. M. Patil Medical College, Hospital and Research Centre, Vijayapura, India. A total of 76 laboratory-confirmed casesof amitraz poisoning admitted to our hospital between January 2014 and March 2024 were included. All patients were analysed for symptoms, signs, laboratory abnormalities, complications, and management protocols. The data was analysed for frequency, percentage, mean, median, mode, standard deviation, and minimumand maximum values using IBM SPSS Statistics, version 26. Results Amitraz poisoningwas most commonly observed in patients aged 20-29 years (36.8%); approximately 23.7% were younger than 20 years. The incidence was the lowest (9.2%) in people who were older than 60 years. A total of 97.4% of patients were from rural areas; out of 76, 50% were male patients and the remaining female patients. The most common presentation was vomiting (90.8%), followed by loss of consciousness (31.6%) and drowsiness (23.7%). Miosis was the most common sign seen in 73.7% of patients, 3.9% had mid-dilated pupils, 5.2% had mydriasis, and 17.1% had normal pupils. In total, 32.9% had hypotension, 10.5% had hypertension and 15.8% had hypothermia; 7.9% of patients had pneumonitis as found on chest X-rays, whereas X-rays of 1.3% patients showed pulmonary edema. ECG findings showed sinus tachycardia in 32.8% of patients, sinus bradycardia in 18.4%, and tall T-waves in only 1.3%, whereas 47.4% had a normal sinus rhythm. Around 39.5% had metabolic acidosis, and 9.2% had metabolic alkalosis based on arterial blood gas analysis. A total of 28.9% of patients needed mechanical ventilation. It was found that 96% of the patients recovered and 2.6% succumbed to death. Also, a patient'saverage stay in the hospital was 4.83±2.4 days. Conclusion The research emphasizes the importance of prompt gastric lavage to mitigate the hazardous effects of amitraz. Despite the lack of an antidote, supportive treatment is necessary to address cardiac effects like bradycardia and hypotension, as well as central nervous systemdepression and respiratory failure. Even though amitraz intoxication has a benign prognosis, these cases are to be closely observed and monitored in intensive care units.

Protective Effects of Lemna minor Linn. On Hepatic and Cognitive Impairments in Acetaminophen Induced Hepatic Encephalopathy in Rats

Aim: Lemna minor Linn., an aquatic plant, is a promising novel therapeutic agent that has been traditionally used in ethnobotanical practices as an ecofriendly supplement for the management of various ailments. This study involves the evaluation of ethanolic extract of Lemna minor Linn. against Paracetamol-induced Hepatic Encephalopathy using in vitro and in vivo Models. Methods: The acute oral toxicity study of the ethanolic extract of Lemna minor (EELM) was conducted following the OECD-425 guidelines over a 14-day period. A total of nine animals were used for this toxicity assessment. The EELM was tested in Paracetamol(PCM)-induced bioactivation animal model at two different dosages 200 and in comparison with silymarin as a standard compound. The In vivo experimental study was conducted using Sprague Dawley rats which was divided into 5 groups each group containing 6 animals so the total no of animals used in the study was 30 animals. The treatment groups included: normal control ( ), 100mg/kg silymarin (standard) and the EELM of two different doses of 200 and , p.o were administered to rats 10 hr before paracetamol ( ) treatment. Rats were orally administered their respective doses every day for total 30days. Paracetamol-induced oxidative liver damage disrupted normal levels of liver enzymes, total protein, and bilirubin, while also depleting antioxidant reserves. This oxidative stress was strongly associated with paracetamol toxicity, leading to a marked depletion of glutathione (GSH) and impairing both memory and cognitive function in the animals. Behavioral parameters are performed to evaluate the effect of drugs on cognitive behaviour of animals. Morris water maze test was performed to study how animals learn and remembers the spatial information relying on distal cues to locate the hidden platform in an opaque water. Additionally, elevated plus maze was performed to measures the anxious behaviour of rats, the criterion was tested based on the conflict between rats innate instincts to explore new environment and avoid open, well-lit areas. The potential protective effects of EELM was evaluated by measuring serum enzyme levels and antioxidants status in the liver and brain, further histopathological analysis was performed respectively. Results: The acute toxicity study did not report any mortality or toxicity signs in animals. PCM toxicity led to a statistically increase in the liver and body weight, along with brain water content. The PCM-intoxicated group exhibited a marked reduction in the level of superoxide dismutase (SOD) and glutathione (GSH) in the brain and liver, as well as an increase in lipid peroxidation and serum biomarkers (AST, ALT, ALP, and total bilirubin). EELM significantly ( ) reduced liver injury by inhibiting ALT, AST and ALP levels in serum. SOD, GSH and MDA liver content were significantly ( ) elevated by EELM, compared to PCM treated rats. Comparing the treatment and induced group, the treated group successfully recovered the activity of antioxidant levels and also been acknowledged for restored liver functioning by alleviating oxidative stress and also GSH level in brain was significantly increased by EELM and preserved the histology of brain, which was chronically produced over a period of 30 days. Conclusion: The findings of this investigation indicate the traditional use of Lemna minor in hepatoprotection and neuroprotection by regulating oxidative stress and mitigating reactive oxygen species (ROS). The insights gained from this research contribute to the development of novel therapeutic agents and paves the way for further studies on Lemna minor to enhance health outcomes, particularly in the management of neurodegenerative diseases.

Enhanced Organics Removal Using 3D/GAC/O3 for N-Containing Organic Pharmaceutical Wastewater: Accounting for Improved Biodegradability and Optimization of Operating Parameters by Response Surface Methodology

Pharmaceutical industry effluents often contain high concentrations of refractory organic solvents, chemical oxygen demand (COD), and total dissolved solids (TDSs). These wastewaters, including N-containing organic solvents known for their persistence and toxicity, pose significant environmental challenges. The study evaluated the efficacy of 3D/Granular Activated Carbon (GAC)/O3 treatment compared to linear process additions when treating real pharmaceutical wastewater, and revealed a 2.73-fold enhancement in COD mineralization. The process primarily involves the direct oxidation of monoprotic organic acids found in real pharmaceutical effluents, such as acetic and formic acid, crucially influencing mineralization rates. Optimal conditions determined via the response surface methodology were 125 g/L GAC, 30 mA/cm2, and 75 mg/L O3, achieving high total organic carbon (TOC) and COD removal efficiencies of 87.19 ± 0.19% and 89.67 ± 0.32%, respectively (R2 &gt; 0.9), during verification runs. Current density emerged as the key parameter for organic abatement, aligning with the emphasis on direct oxidation at the anode surface. This integrated approach enhances biodegradability (BOD5/COD) and reduces acute toxicity associated with persistent N-containing solvents, demonstrating promising applications in pharmaceutical wastewater treatment.

A novel integrated testing strategy (ITS) for evaluating acute fish toxicity with new approach methodologies (NAMs)

Acute fish toxicity (AFT) tests are performed in aquatic risk assessments of chemical compounds globally. However, the specific endpoint of in vivo AFT is based on the lethal concentration 50 (LC50), which is a serious challenge in terms of animal welfare. To support the 3Rs principle of replacing, reducing, and refining use of animals, integrated testing strategies (ITS) have recently been developed for environmental risk assessment. ITS efficiently integrates multiple types of information, especially new approach methodologies (NAMs), and further supports regulatory decision-making. Currently, an effective ITS framework for evaluating aquatic toxicity is lacking. Therefore, we aimed to develop a promising ITS for AFT using in silico, in vitro, and in vivo data. We established the ITS via in silico (OECD QSAR Toolbox 4.6), fish cell line acute toxicity (FCT), and fish embryo acute toxicity (FET) tests and then validated the NAMs with AFT testing. The NAM data were derived from the European Chemicals Agency (ECHA) dossier, toxicology databases, peer-reviewed research articles, and this study. For the first step in the ITS process, we aimed to design a high-throughput screening tool to identify non-toxic and toxic chemicals. We found that results of in silico, FCT, and FET tests alone were strongly correlated with AFT. Among the models, the in silico model was most suitable for identifying toxicants due to its high sensitivity and minimal animal use. Next, considering regulatory purposes and flexibility, we determined the predictive LC50 of toxic chemicals by pursuing a preference-dependent strategy, sequential testing strategy, and sensitivity-dependent strategy. All the strategies demonstrated a predictive power equal to or greater than 73%. In addition, to meet user preferences, our ITS approach has high flexibility and supports animal welfare and environmental protection. We have therefore developed multiple powerful, flexible, and more humane ITS methods for acute fish toxicity assessment by integrating NAMs.

Sub-chronic and acute toxicity of aqueous extracts Salvia blancoana subsp. mesatlantica (Maire) Figuerola to rodents

BackgroundSalvia blancoana subsp. mesatlantica (Maire) Figuerola (SBm) is a plant endemic to Morocco and is one of the less studied species of Salvia. Herbal therapy is becoming more and more popular, especially in underdeveloped nations where access to medicinal herbs is affordable. However, some plants demonstrated toxic effects in animals and humans. ObjectiveOur study aimed to evaluate the SBm-extract for both acute and sub-chronic toxicity. MethodsAqueous extracts were obtained from the aerial parts of SBm collected from Immouzer Kander commune (Middle Atlas, Morocco). Total Phenolic Content (TPC) and Flavones and flavonols Content (FFC), Antioxidant activity (2,2-diphenyl-1-picrylhydrazyl (DPPH) and reducing power) was determined, and chemical composition was determined by High-Performance Liquid Chromatography with Diode Array Detection (HPLC-DAD). Toxicity tests were conducted on mice and rats. ResultsIn acute toxicity, Swiss albino mice (mass of 25-35g) received SBm-extract orally and intraperitoneally at doses (0.5 to 11g/kg, bm). The sub-chronic toxicity was tested in Wistar albino rats (mass of 200-240g) for 90 days at doses of 0, 250, 500, or 1000mg/kg, bm. Values of TPC and FFC were estimated to be 157.56 ± 0.32mg GAE/g DW and 7.89 ± 0.05mg QE/g DW, respectively. DPPH scavenging (IC50) was estimated to be 26.9 ± 0.08µg/mL while reducing power was 12.41 ± 0.03µg/mL. No toxicity or deaths were observed in acute tests after oral exposure, while intraperitoneal administration resulted in dose-dependent acute toxicity, with an LD50 value of 6.82g/kg. In sub-chronic tests, most hematological and biochemical parameters remained unchanged, except for transient fluctuations in specific blood constituents and a transitory reduction in serum glucose levels observed at elevated dosages. Histopathological investigation revealed no organ abnormalities. The SBm-extract exhibited minimal toxicity, supporting its safe use. ConclusionsDespite the relevant results of this study, future studies need to confirm these findings and expand our understanding of the safety characteristics of Salvia. Further investigations are needed to explore the effects of other solvents on the extraction of bioactive compounds from the underground and aerial parts of this endemic species. Evaluation of other biological properties such as anti-microbial, anti-cancer, and anti-inflammatory activities are needed.