Potential Acute Toxicity Research Articles

In vitro cyto- and geno-toxicity of asbestiform erionite from New Zealand

This work is an in vitro toxicity study of two asbestiform erionites from Kaipara and Gawler Downs in New Zealand. This study is the first, to the knowledge of the authors, to investigate the mechanisms that trigger adverse effects leading to carcinogenicity from New Zealand erionites. The effects induced by the erionite fibres from New Zealand were compared with those produced by positive (crocidolite) and negative (wollastonite) standards, and other erionite fibres described in the literature. The cytotoxicity/genotoxicity/inflammatory potential was determined by: (i) analysis of the cytotoxic potential by MTT tests on human cell lines mimicking primary cells making direct contact with fibres in the lungs, combined with apoptosis tests and cell membrane damage by fluorescence microscopy analyses; (ii) analysis of the genotoxic potential by quantification of DNA damage measuring double strand break foci by γ-H2AX nuclear staining in confocal microscopy analyses; (iii) analyses of the acute (24–72h) and early-chronic (7d) inflammatory effect by gene expression analyses of several cytokines, as well as of fibrotic and Epithelial to Mesenchymal transition (EMT) markers. The intensity of cell responses to these erionites are comparable to that of standard carcinogenic crocidolite, indicating that the two erionite fibres exhibit a significant acute toxic potential, with a particular alarming effect from the Gawler Downs sample from South Island. Our results confirm that the investigated erionites from New Zealand may represent an environmental hazard. However, further investigation is required to determine potential environmental exposure pathways by which erionite may become airborne and assess any environmental risks that may arise.

Chemical characterization, assessment of acute oral toxicity, and antinociceptive potential of the methanolic extract of Montrichardia linifera (Arruda) Schott leaves from Brazil.

Montrichardia linifera (Arruda) Schott is popularly known as "aninga," "aningaçu," "aningaíba," and "aninga-do-igapó." Compresses and plasters made from the leaves of this medicinal plant are used to treat abscesses, tumors, and pain caused by stingray stings. This study aimed to chemically characterize the methanolic extract of M. linifera leaves (MEMLL), as well as to verify their acute oral toxicity and antinociceptive potential. The leaves were collected during the rainy season, and the methanolic extract was obtained after gradient extraction using different solvents. MEMLL was analyzed using high-performance liquid chromatography (HPLC) and nuclear magnetic resonance (NMR). Acute oral toxicity testing followed the Organization for Economic Co-operation and Development (OECD) guideline 423. Subsequently, acetic acid, hot plate, and formalin tests were used to evaluate the analgesic effects. In the chemical characterization of MEMLL by HPLC, three flavonoids were identified: rutin, quercetin, and epicatechin. In addition, when NMR spectroscopy was performed, rutin and quercetin were again identified, as well as the chemical compounds luteolin and chrysoeriol. In the acute oral toxicity test, MEMLL showed no physiological or behavioral changes. In the nociceptive study, MEMLL showed an effect at doses of 50 and 100mg/kg in the 0.6% acetic acid test, i.e., 51.46% and 75.08%, respectively. In the hot plate test, the MEMLL group at a dose of 50mg/kg was effective at times of 30 and 60min, i.e., 164.43% and 122.95%, respectively. Similarly, the MEMLL group at a dose of 100mg/kg was also effective in increasing latency at times of 30 and 60min, i.e., 162.62% and 136.68%, respectively. In the formalin test, MEMLL showed an antinociceptive effect on neurogenic pain at doses of 50 and 100mg/kg when compared to the control group, 35.25% and 52.30%, respectively. In the inflammatory phase, inhibition was observed in the MEMLL at doses of 50 and 100mg/kg, i.e., 66.39% and 72.15%, respectively. MEMLL has analgesic properties and is non-toxic, validating the Brazilian ethnopharmacological use of this plant for pain treatment. The leaves of the species M. linifera showed central and peripheral antinociceptive effects.

In Vitro Analysis of Benzopyran Derivative's Action Against Aspergillus Species

Objective: The objective of this study is to investigate in vitro activity of two specific benzopyran derivatives: Ethyl 2-(4-oxo-4H-chromen-3-yl)-4,5-dihydrothiazole-4-carboxylate and 2-(4-oxo-4H-chromen-3-yl) thiazolidine., with the aim of ascertaining their minimum inhibitory concentration (MIC) and discerning their cytotoxic effects on human RBCs. Theoretical Framework: Aspergillus fumigatus causes numerous global deaths annually. Its increasing resistance to conventional antifungals and many azoles underscores the urgency for new therapeutic solutions. Method: Compounds were synthesized and we utilized the Disc Diffusion Assay, Microdilution Assay, Spore Germination Inhibition Assay, and Electron Microscopy to assess the anti-Aspergillus effects of PI 103 and PI 105. Additionally, the Hemolytic Assay was conducted to evaluate its potential acute toxicity. Results: The Minimum Inhibitory Concentration (MIC) for PI 103 varied between 15.6 mg/L and 250 mg/L, with no observable activity in two out of thirteen strains. For PI 105, the MIC ranged from 3.9 mg/L to 62.5 mg/L. Research Implications: Both compounds exhibited encouraging outcomes and demonstrated non-toxicity. Future refinements and research could bolster their efficacy. Their safety profile also paves the way for their potential use in a wider range of therapeutic treatments against fungal infections.

Arisarum vulgare: Bridging Tradition and Science Through Phytochemical Characterization and Exploring Therapeutic Potential via In vitro, In vivo, and In silico Biological Activities

AbstractArisarum vulgare O. Targ. Tozz. (Araceae), locally known as “Elbgouga,” holds significant traditional importance in Algeria for the treatment of various human ailments, including pain, infections, inflammation, digestive disorders, cancer, skin problems, eczema, wounds, and burns. The aim of this study was to explore for the first time the phytochemical profile, antioxidant, antibacterial, and inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes, DNA protection, and capacity to promote wound healing. Preliminary phytochemical experiments were conducted to evaluate the major classes of bioactive compounds, in addition to the total phenol and flavonoid amounts in AVEE. An LC‐MS/MS analysis was conducted to clarify the phytochemical composition of this particular botanical species. The antioxidant capacity was assessed using DPPH· and ABTS·+ radical scavenging tests. The agar diffusion approach was used to ascertain the antibacterial efficacy against four bacteria (Staphylococcus aureus, Enterococcus faecium, Escherichia coli, and Salmonella typhimurium). Cholinesterase inhibition was evaluated using a colorimetric method that relies on Ellman's reaction. The protective effects of AVEE on pBR322 plasmid DNA damaged by H2O2 and UV treatment were assessed by their DNA‐breaking forms. The in vivo acute dermal toxicity and wound healing potential of the AVEE ointment (1–5% AVEO) were also investigated, and histological analyses were carried out on biological samples. Five protein targets were the subject of an in silico molecular docking investigation (TNFα, TGFBR1, IL‐1ß, GSK‐3ß, and NOS) and ADMET studies of the main components of the extracts were performed. The screening of phytochemicals revealed a significant concentration of phenolic compounds (176.00 ± 1.08 mg of gallic acid equivalents/g of dry extract), mainly flavonoids (81.21 ± 1.24 mg of quercetin equivalents/g of dry extract). Three major compounds were identified by LC‐MS/MS analysis, belonging mainly to the class of flavonoids, with rutin as the most abundant compound (11.85 mg/g extract), followed by hesperidin (4.125 mg/g extract). A conspicuous presence of isoquercitrin (1.327 mg/g extract) was also found. Small amounts of flavonoids and phenolic acids were also detected (catechin, chlorogenic acid, syringic acid, salicylic acid, kaempferol, and luteolin). DPPH assay showed higher antioxidant capacity compared to the ABTS·+ assay (142.60 ± 5.52 µg/mL and 236.10 ± 0.22 µg/mL, respectively). AVEE was effective against all selected bacterial strains; however, the highest zone of inhibition (36.00 ± 0.1 mm) was noted against E. faecium. The extract of the plant significantly inhibited both AChE and BChE (89.98 ± 18.76 µg/mL inhibitory activity against AChE and 98.28 ± 44.68 µg/mL inhibitory activity against BChE, respectively). The ethanolic extract of A. vulgare and quercetin exhibited more significant DNA protection action in form I, with percentages of 90.41 and 94.23%, respectively, compared to form II, where the percentages were 27.91 and 51.92%, respectively. The AVEO formulation may be safely administered by topical application. A statistically significant wound contraction was discovered in the group treated with 5% AVEO compared to the groups that were not treated or treated with petroleum jelly. Furthermore, there was no notable disparity detected between the group treated with 5% AVEO and the group treated with the reference drug. The 5% AVEO‐treated group showed, after the research was complete, the most significant percentage of wound contraction (96.90 ± 0.42%). Moreover, the topical application of the formulation improved histological parameters. In silico study showed that rutin, hesperidin, and isoquercitrin had a high affinity to the five main targets that might contribute to the wound healing potential of A. vulgare ethanolic extract. The impressive biological capabilities of A. vulgare indicate that the plant has the ability to be a valuable source of bioactive chemicals with various medical applications.

PHYTOCHEMICAL CONSTITUENT, ACUTE TOXICITY AND HYPOGLYCEMIC POTENTIAL OF DICHROSTACHYS CINEREA METHANOL LEAF EXTRACT

Diabetes mellitus (DM) is a major public health problem worldwide, herbal derivatives have proved to be more efficient in the treatment of diabetes over synthetic drugs because of less side effects and adverse effects. The aim of this article is to investigate the phytochemical constituent, acute toxicity and hypoglycemic potential of Dichrostachys cinerea methanol leaf extract. Standard laboratory protocols were employed for phytochemical assay, fixed dose method was used to determine acute toxicity (LD50). Alloxan was used to induce diabetes to experimental animals and fasting blood levels were recorded weekly using glucometer. Phytochemical analysis revealed the presence of numerous phytoconstituents. The result for acute toxicity of D. cinerea methanol leaf extract (DCME) showed that the LD50 is above 5000mg/kg. The body weight showed that there were no significant (P>0.05) difference in untreated control, standard control, DCME100mg/kg, DCME200mg/kg, DCME 400mg/kg and normal control initially. At week 1, 2 and 3, only group treated with standard drug and extract significantly (P<0.05) increases compared to both normal and untreated control. Before extract and standard drug administration (week 0), the fasting blood sugar of all the alloxan diabetes induced groups (i.e group 2, 3, 4, 5 and 6) significantly (P<0.05) increased compared to normal control group. After week 1, 2 and 3 of treatment there was no significant (P>0.05) difference between, extract treated groups compared to standard control. The present study revealed that D. cinerea methanol leaf extract contain numerous phytochemicals and the extract is practically not toxic at acute dose, and with strong glucose lowering potentials.

Prediction of chemical-induced acute toxicity using in vitro assay data and chemical structure

Exposure to various chemicals found in the environment and in the context of drug development can cause acute toxicity. To provide an alternative to in vivo animal toxicity testing, the U.S. Tox21 consortium developed in vitro assays to test a library of approximately 10,000 drugs and environmental chemicals (Tox21 10K compound library) in a quantitative high-throughput screening (qHTS) approach. In this study, we assessed the utility of Tox21 assay data in comparison with chemical structure information in predicting acute systemic toxicity. Prediction models were developed using four machine learning algorithms, namely Random Forest, Naïve Bayes, eXtreme Gradient Boosting, and Support Vector Machine, and their performance was assessed using the area under the receiver operating characteristic curve (AUC-ROC). The chemical structure-based models as well as the Tox21 assay data demonstrated good predictive power for acute toxicity, achieving AUC-ROC values ranging from 0.83 to 0.93 and 0.73 to 0.79, respectively. We applied the models to predict the acute toxicity potential of the compounds in the Tox21 10K compound library, most of which were found to be non-toxic. In addition, we identified the Tox21 assays that contributed the most to acute toxicity prediction, such as acetylcholinesterase (AChE) inhibition and p53 induction. Chemical features including organophosphates and carbamates were also identified to be significantly associated with acute toxicity. In conclusion, this study underscores the utility of in vitro assay data in predicting acute toxicity.

Investigating the ecological and toxicological significance of Cyanox®53 recovered from intertidal sediments and varnish clam

We examined the ecological and toxicological implications of the microplastic, Cyanox®53, found in sediments and varnish clams across seven beaches in Burrard Inlet, British Columbia (BC). Using the simulation models embedded within Estimation Programs Interface (EPI) Suite™, the potential persistence, bioaccumulation, and toxicity of Cyanox®53 was assessed to evaluate the risk to varnish clams foraging on sediment containing this contaminant. Moreover, we used a bioenergetic model, based on the blue-listed surf scoter species, to estimate the risk of daily ingestion of Cyanox®53 per body weight in overwintering seabirds. Our findings indicate that varnish clams collected from Burrard Inlet accumulate on average 0.46 particles of Cyanox®53/clam, and based on bioenergetic modeling, results in surf scoters potentially consuming 78 (for males) to 83 (for females) pieces of Cyanox®53 daily from foraged varnish clams. EPI Suite™ predicted Cyanox®53 to be persistent, however, unlikely to bioaccumulate as a “traditional” chemical. Furthermore, the estimation of potential acute and chronic toxicity of Cyanox®53 to aquatic organism surrogates, such as fish, Daphnia magna, and green algae, was inconclusive due to model variability and limitations within EPI Suite™. To fully understand the potential risks of Cyanox®53 further investigation is warranted.

Synthesis, Characterization, Acute Dermal Toxicity, Anti-inflammatory, and Wound Healing Potential of Biogenic Silver Nanoparticles in Balb C Mice.

The current study aimed to develop an economic plant-based therapeutic agent to improve the treatment strategies for diseases at the nano-scale. In the current research, silver nanoparticles were synthesized using Trillium govanianum aqueous extract. Characterizations were done using UV-visible spectrophotometer, X-ray diffraction, scanning electron microscopy, and Fourier transform infrared spectroscopy. In vivo biological activities such as acute dermal toxicity, wound healing, and anti-inflammatory were done on Balb C mice. Absorbance at 295 nm corresponds to the out-of-plane quadrupole Plasmonresonance while at 350 nm corresponds to in-plane dipole resonance. SEM images showed the morphology of TGAgNPs is not exactly spherical while XRD analysis shows that highly crystalline TGAgNPs with an average size of 27.94 nm. The FTIR spectrum represents sharp peaks of aldehyde, amide I, aromatic rings, and polysaccharides. The microscopic assessment did not find any epidermal and dermal layer abnormalities in Blab C mice when exposed to TGAgNPs during acute dermal toxicity. Results revealed that 1000 mg/kg is not a lethal dose. In the wound healing activity, no mortality and no abnormal signs were observed when petroleum jelly, nitrofuranose, TGaqu, and TGAgNPs-based ointments were applied. Enhanced epithelization was recorded in TGaqu and TGAgNPs treated mice (p≤0.001). The wound contraction percentage was higher in nitrofuranose-treated mice (74%) followed by TGAgNPs (71%), and TGaqu (69%) compared to vehicle-treated and open-wounded mice. The paw edema model proved the potential use of TGAgNPs and TGaqu as anti-inflammatory agents. Hence, the results proved that both TGaqu and TGAgNPs are not toxic and possessed strong anti-inflammatory and wound-healing effects due to the presence of phytochemical constituents and could be used in various drug production as a therapeutic agent.

Acute Toxicity, Anti-diabetic, and Anti-cancerous Potential of Trillium Govanianum-conjugated Silver Nanoparticles in Balb/c Mice.

The current study aimed to develop an economic plant-based therapeutic agent to improve the treatment strategies for diseases at the nano-scale because Cancer and Diabetes mellitus are major concerns in developing countries. Therefore, in vitro and in vivo antidiabetic and anti-cancerous activities of Trillium govanianum conjugated silver nanoparticles were assessed. In the current study synthesis of silver nanoparticles using Trillium govanianum and characterization were done using a scanning electron microscope, UV-visible spectrophotometer, and FTIR analysis. The in vitro and in vivo anti-diabetic and anti-cancerous potential (200 mg/kg and 400 mg/kg) were carried out. It was discovered that Balb/c mice did not show any major alterations during observation of acute oral toxicity when administered orally both TGaqu (1000 mg/kg) and TGAgNPs (1000 mg/kg), and results revealed that 1000 mg/kg is not lethal dose as did not find any abnormalities in epidermal and dermal layers when exposed to TGAgNPs. In vitro studies showed that TGAgNPs could not only inhibit alpha-glucosidase and protein kinases but were also potent against the brine shrimp. Though, a significant reduction in blood glucose levels and significant anti-cancerous effects was recorded when alloxan-treated and CCl4-induced mice were treated with TGAgNPs and TGaqu. Both in vivo and in vitro studies revealed that TGaqu and TGAgNPs are not toxic at 200 mg/kg, 400 mg/kg, and 1000 mg/kg doses and possess strong anti-diabetic and anti-cancerous effects due to the presence of phyto-constituents. Further, suggesting that green synthesized silver nanoparticles could be used in pharmaceutical industries to develop potent therapeutic agents.

Antimalarial efficacy test of the aqueous crude leaf extract of Coriandrum sativum Linn.: an in vivo multiple model experimental study in mice infected with Plasmodium berghei

BackgroundMalaria continues to wreak havoc on the well-being of the community. Resistant parasites are jeopardizing the treatment. This is a wake-up call for better medications. Folk plants are the key starting point for antimalarial drug discovery. After crushing and mixing the leaves of Coriandrum sativum with water, one cup of tea is drunk daily for a duration of three to five days as a remedy for malaria by local folks in Ethiopia. Additionally, in vitro experiments conducted on the plant leaf extract elsewhere have also demonstrated the plant’s malaria parasite inhibitory effect. There has been no pharmacologic research to assert this endowment in animals, though. This experiment was aimed at evaluating the antimalarial efficacy of C. sativum in Plasmodium berghei infected mice.MethodsThe plant's leaf was extracted using maceration with distilled water. The extract was examined for potential acute toxicity. An evaluation of secondary phytoconstituents was done. Standard antimalarial screening models (prophylactic, chemosuppressive, curative tests) were utilized to assess the antiplasmodial effect. In each test, thirty mice were organized into groups of five. To the three categories, the test substance was given at doses of 100, 200 and 400 mg/kg/day before or after the commencement of P. berghei infection. Positive and negative control mice were provided Chloroquine and distilled water, respectively. Rectal temperature, parasitemia, body weight, survival time and packed cell volume were ultimately assessed. Analysis of the data was performed using Statistical Package for Social Sciences.ResultsNo toxicity was manifested in mice. The extract demonstrated a significant inhibition of parasitemia (p < 0.05) in all the models. The inhibition of parasite load was highest with the upper dose in the suppressive test (82.74%) followed by the curative procedure (78.49%). Likewise, inhibition of hypothermia, weight loss hampering, improved survival and protection against hemolysis were elicited by the extract.ConclusionsThe results of our experimental study revealed that the aqueous crude leaf extract of C. sativum exhibits significant antimalarial efficacy in multiple in vivo models involving mice infected with P. berghei. Given this promising therapeutic attribute, in depth investigation on the plant is recommended.

Ecotoxicity and environmental safety assessment of two-dimensional niobium carbides (MXenes)

Two-dimensional (2D) MXenes have gained great interest in water treatment, biomedical, and environmental applications. The antimicrobial activity and cell toxicity of several MXenes including Nb4C3Tx and Nb2CTx have already been explored. However, potential side effects related to Nb-MXene toxicity, especially on aquatic pneuma, have rarely been studied. Using zebrafish embryos, we investigated and compared the potential acute toxicity between two forms of Nb-MXene: the multilayer (ML-Nb4C3Tx, ML-Nb2CTx) and the delaminated (DL-Nb2CTx, and DL-Nb4C3Tx) Nb-MXene. The LC50 of ML-Nb4C3Tx, ML-Nb2CTx, DL-Nb2CTx, and DL-Nb4C3Tx were estimated to be 220, 215, 225, and 128 mg/L, respectively. Although DL-Nb2CTx, and DL-Nb4C3Tx derivatives have similar sizes, DL-Nb4C3Tx not only shows the higher mortality (LC50 = 128 mg/L Vs 225 mg/L), but also the highest teratogenic effect (NOEC = 100 mg/L Vs 200 mg/L). LDH release assay suggested more cell membrane damage and a higher superoxide anion production in DL-Nb4C3Tx than DL-Nb2CTx,. Interestingly, both DL-Nb-MXene nanosheets showed insignificant cardiac, hepatic, or behavioral toxic effects compared to the negative control. Embryos treated with the NOEC of DL-Nb2CTx presented hyperlocomotion, while embryos treated with the NOEC of DL-Nb4C3Tx presented hyperlocomotion, suggesting developmental neurotoxic effect and muscle impairment induced by both DL-Nb-MXene. According to the Fish and Wildlife Service (FSW) Acute Toxicity Rating Scale, all tested Nb-MXene nanosheets were classified as “Practically not toxic”. However, DL-Nb4C3Tx should be treated with caution as it might cause a neurotoxic effect on fauna when it ends up in wastewater in high concentrations.

Acute Dermal Toxicity of Liquid Smoke (Cocos nucifera L.) Grade 1

Liquid smoke, a product from coconut shell waste, is a food preservative and antimicrobial substitute. It is produced through pyrolysis at 400-600°C, producing solid, liquid, and gas products. Toxicity studies need to be conducted to test the safety of medicinal products. This is because medicinal products that meet the requirements are those that have proven their efficacy and safety. Liquid smoke, especially grade 1, has not been studied further regarding its safety. This study aimed to determine the acute toxicity potential of grade 1 coconut shell liquid smoke. The experimental method involved collecting and processing samples, making liquid smoke, purifying them, and testing the effects of acute dermal toxicity. Results showed mild damage to liver and kidney organs, with microscopic liver tissue damage and kidney tissue damage. Keywords: Cocos nucifera L., liquid smoke, toxicity, acute, subchronic

The estimation of acute oral toxicity (LD50) of G-series organophosphorus-based chemical warfare agents using quantitative and qualitative toxicology in silico methods.

The idea of this study was the estimation of the theoretical acute toxicity (t-LD50, rat, oral dose) of organophosphorus-based chemical warfare agents from the G-series (n = 12) using different in silico methods. Initially identified in Germany, the G-type nerve agents include potent compounds such as tabun, sarin, and soman. Despite their historical significance, there is a noticeable gap in acute toxicity data for these agents. This study employs qualitative (STopTox and AdmetSAR) and quantitative (TEST; CATMoS; ProTox-II and QSAR Toolbox) in silico methods to predict LD50 values, offering an ethical alternative to animal testing. Additionally, we conducted quantitative extrapolation from animals, and the results of qualitative tests confirmed the acute toxicity potential of these substances and enabled the identification of toxicophoric groups. According to our estimations, the most lethal agents within this category were GV, soman (GD), sarin (GB), thiosarin (GBS), and chlorosarin (GC), with t-LD50 values (oral administration, extrapolated from rat to human) of 0.05mg/kg bw, 0.08mg/kg bw, 0.12mg/kg bw, 0.15mg/kg bw, and 0.17mg/kg bw, respectively. On the contrary, compounds with a cycloalkane attached to the phospho-oxygen linkage, specifically methyl cyclosarin and cyclosarin, were found to be the least toxic, with values of 2.28mg/kg bw and 3.03mg/kg bw. The findings aim to fill the knowledge gap regarding the acute toxicity of these agents, highlighting the need for modern toxicological methods that align with ethical considerations, next-generation risk assessment (NGRA) and the 3Rs (replacement, reduction and refinement) principles.

Acute Toxicity Assessment of Orally Administered Microplastic Particles in Adult Male Wistar Rats.

While the effects of chronic exposure to microplastic particles (MPs) are extensively studied, the outcomes of a single treatment have received relatively less attention. To investigate MPs' potential acute toxicity, including their impact on general health status (victual consumption, sensorimotor deficits, and clinical toxicity signs) and serum biochemical parameters (markers of organ/tissue function and oxidative stress indicators), we administered thoroughly characterized MPs (1.4, 35, or 125 mg/kg), generated from polyethylene terephthalate (PET) bottles, to adult male Wistar rats via oral gavage. The MPs' short-term effects were assessed with well-established tests and methods. The results point to the absence of sensorimotor deficits and clinical toxicity signs, while levels of markers of liver, heart, and kidney function were altered in all MP groups. Decreased victual consumption and increased levels of oxidative stress indicators were evident following treatment with the two higher MP doses. Presented data indicate that examined MPs are able to initiate the development of local changes in tissues and organs within a short time frame, potentially leading to their damage and dysfunction. This study may increase the awareness of the detrimental effects of plastic contamination, as even a single exposure to MPs may provoke adverse health outcomes.

Safety evaluation of Gamisoyo-san: genotoxicity, acute toxicity, and influence on drug-metabolizing enzymes

Gamisoyo-san is an herbal formula widely used to treat psychological issues, menopausal symptoms, and dysmenorrhea. However, there is insufficient information on its safety profile. This study aimed to confirm the genotoxic and acute toxic potential of Gamisoyo-san. We performed a battery of tests, which included a bacterial reverse mutation test (Ames test) using five bacterial strains, an in vitro chromosomal aberration test using Chinese hamster lung (CHL) cells, an in vivo micronucleus test in mice, and human Cytochrome P450 (CYP450) and UDP-glucuronosyltransferase (UGT) assays. In the acute toxicity study, male and female rats were orally administered Gamisoyo-san 1000, 2000, or 5000 mg/kg and observed for 14 days. The activities of human CYP450s and UGTs were evaluated using recombinant baculosomes. Gamisoyo-san showed no signs of genotoxicity in the five bacterial strains, CHL cells, or mouse bone marrow cells. The acute toxicity test showed that the median lethal dose (LD50) of Gamisoyo-san was greater than 5000 mg/kg in rats. Gamisoyo-san inhibited the activities of CYP1A2, CYP2C19, and UGT1A1. In conclusion, Gamisoyo-san may not exert severe toxicological events or genotoxic effects at doses up to 5000 mg/kg in rats.

Assessment of toxicity, genotoxicity and oxidative stress in Fejervarya limnocharis exposed to tributyltin.

Tributyltin (TBT) is widely used in various commercial applications due to its biocidal properties. Toxicological and genotoxicological data on TBT exposure to amphibians is insufficient. Our study aimed to determine the acute toxicity and genotoxic potential of TBT in Fejervarya limnocharis tadpoles. Furthermore, oxidative stress was also investigated in TBT-treated tadpoles. Tadpoles of Gosner stage (26-30) were screened and subjected to increasing concentrations of TBT (0, 3, 7, 11, 15, 19, 23µg/L) for determining the LC50 values for 24h, 48h, 72h, and 96h. LC50 values of TBT for 24h, 48h, 72h, and 96h were found to be 19.45, 15.07, 13.12, and 11.84μg/L respectively. Based on the 96h LC50 value (11.84µg/L), tadpoles were exposed to different sub-lethal concentrations of TBT for the evaluation of its genotoxic potential and effects on oxidative balance. The role of TBT on survivability, growth, and time to metamorphosis was also assessed. TBT exposure significantly altered the life history traits measured, increased mortality, and delayed the time taken to metamorphosis. Results indicated significant induction of micronucleus (MN, p < 0.001) and other erythrocytic nuclear aberrations (ENA, p < 0.01) in the TBT-treated groups. Significant alterations in comet parameters and oxidative balance were also observed in the treated groups. The present study findings might add to the cause of the gradual population decline seen in the amphibians. This study also demonstrates the alteration of the life-history traits, oxidative balance, and DNA damage upon TBT exposure which can have long-term consequences for the anuran amphibian F. limnocharis.

GC-MS analysis of organic fractions of Chrozophora tinctoria (L.) A.Juss. and their prokinetic propensity in animal models.

Chrozophora tinctoria (L.) A.Juss. is herbaceous, monecious annual plant used traditionally to cure gastrointestinal disorders. The present study was carried out to find the bioactive compounds by Gas Chromatography-Mass Spectrometry, the acetylcholinesterase inhibitory potential acute toxicity, and emetic activity present in the ethyl acetate fraction of Chrozophora tinctoria (EAFCT) and dichloromethane fraction of Chrozophora tinctoria (DCMFCT). The compounds detected in both fractions were mostly fatty acids, with about seven compounds in EAFCT and 10 in DCMFCT. These included pharmacologically active compounds such as imipramine, used to treat depression, or hexadecanoic acid methyl ester, an antioxidant, nematicide, pesticide, hypocholesterolemic, 9,12,15-Octadecatrienoic acid, ethyl ester, (Z,Z,Z)- is used as a cancer preventive, antiarthritic, antihistaminic, hepatoprotective, insectifuge, nematicide, Pentadecanoic acid, 14-methyl-, methyl ester have antifungal, antimicrobial and antioxidant activities, 10-Octadecanoic acid, methyl ester have the property to decrease blood cholesterol, Antioxidant and antimicrobial, 1-Eicosanol is used as an antibacterial, 1-Hexadecene has antibacterial, antioxidant, and antifungal activities. Both DCMFCT and EAFCT fractions inhibited acetylcholinesterase (AChE) activity with IC50 values of 10 µg and 130 µg, respectively. Both the fractions were found to be toxic in a dose-dependent manner, inducing emesis at 0.5g onward and lethargy and mortality from 3-5 g upwards. Both the fractions combined with distilled water showed highly emetic activity. The significant increase in the number of vomits was shown by EAFCT plus distilled water which are 7.50±1.29, 7.25±3.10, and 11.75±2.22 number of vomits at 1g, 2g, and 3g/kg concentration respectively, while DCMFCT plus distilled water showed 5.25±2.22, 7.50±2.52 and 10.25±2.22 number of vomits at 1g, 2, and 3g/kg correspondingly. The antiemetic standard drug metoclopramide has a higher impact against the emesis induced by both the fractions than dimenhydrinate. Metoclopramide decreases the number of vomits caused by EAFCT to 1.00±0.00, 2.00±0.00, 4.00±1.00 at 1g, 2, and 3g/kg sequentially, while dimenhydrinate decreases the number of vomits to 1.33±0.58, 2.33±1.15, 4.33±0.58 at 1g, 2, and 3g respectively. In the same way, Metochloprimide decreases the number of emesis caused by DcmCt from 5.25±2.22, 7.50±2.52, 10.25±2.22 to 1.33±0.58, 2.33±1.1, 4.33±0.58 at 1g, 2, and 3g/kg concentrations. The present study is the first documented report that scientifically validates the folkloric use of Chrozophora tinctoria as an emetic agent.

Tapping the Tunisian sunlight's potential to remove pharmaceuticals in tap water and secondary effluents: A comparison of Ag2O/TiO2 and BiOI photocatalysts and toxicological insights

In this study, BiOI microspheres and the Ag2O/TiO2 heterostructure were synthesized to photocatalytically degrade atenolol (ATL) and carbamazepine (CBZ) in tap water and secondary effluent under Tunisian summer season sunlight. The materials were characterized through XRD, SEM, TEM and DRS. The Ag2O/TiO2 material excelled by completely removing both pharmaceuticals from tap water within 180 min of irradiation, while less than 20 % of CBZ persisted in effluent after 3 h of irradiation. Stability tests using the Ag2O/TiO2 heterostructure over five reaction cycles indicated consistent degradation rates for ATL (k ranged from 3.1 × 10-2 to 5.9 × 10-2 min−1). Conversely, CBZ degradation rates increased from k = 6.4 × 10-3 min−1 to k = 1.8 × 10-2 min−1 in the fifth cycle. This increase was attributed to changes in the oxidation state of silver nanoparticles deposited on TiO2. Quenching tests identified OH radicals as dominant in photocatalytic degradation, followed by photo-holes for CBZ, and O2− radicals for ATL. Through LC-MS/MS, degradation byproducts were identified, allowing for proposed degradation kinetics. Lastly, the toxicity of the byproducts was estimated using the ECOSAR model, displaying a decrease in the toxicity of hydroxylated intermediates, while aminated species represented higher potential for acute and chronic toxicity.

Harnessing the Reactivity of Duclauxin toward Obtaining hPTP1B1-400 Inhibitors.

Duclauxin (1) from Talaromyces sp. IQ-313 was reported as a putative allosteric modulator of human recombinant protein tyrosine phosphatase 1B (400 amino acids) (hPTP1B1-400), a validated target for the treatment of type II diabetes. Based on these findings, a one-strain-many-compound (OSMAC) experiment on the IQ-313 strain generated derivatives 5a, 6, and 7. Moreover, a one-/two-step semisynthetic approach guided by docking toward hPTP1B1-400 produced 38 analogs, a series (A) incorporating a lactam functionalization at C-1 (8a-15a, 36a, and 37a) and a series (B) containing a lactam at C-1 and an extra unsaturation between C-7 and C-8 (5b, 11b-37b). In vitro evaluation and structure-activity relationship (SAR) analysis revealed that analogs from the B series are up to 10-fold more active than 1 and derivatives from the A series. Furthermore, duclauxin (1) and 36b were assessed for their potential acute toxicity, estimating their LD50 to be higher than 300 mg/kg. Moreover, 36b significantly reduced glycemia in an insulin tolerance test in mice, suggesting that its mechanism of action is through the PTP1B inhibition.

Comparison of Acute Toxicity Test of Cardamom Extract Combination and Curcuma with a Combination of Cardamom Extract and Galangal against Artemia salina Leach by Brine Shrimp Lethality Test Method

Cardamom, ginger, and galangal are one of the plants that are often used as herbal medicine. Similar studies that have been carried out previously only conducted single extract tests and have not combined extracts, and compared the results of using two combinations of extracts. However, because there is a possibility of interactions between compounds in a single extract that can increase their toxic effects, it is necessary to conduct acute toxicity testing of the combination aimed at determining the potential toxicity. This study aims to determine the comparison of the potential acute toxicity of cardamom and curcuma extract combinations with cardamom and galangal extract combinations seen from LC50 values using the Brine Shrimp Lethality Test (BSLT) method. The research conducted was an experimental study, extracted by maceration method and using BSLT method for toxicity testing. In this study using 5 variations in concentration, but the concentration of extracts used in the combination of extracts is different, namely the combination of cardamom and curcuma extracts using variations in concentrations of 12.5ppm, 25 ppm, 50 ppm, 100 ppm, while the combination of cardamom and galangal extracts uses variations in concentrations of 500 ppm, 250 ppm, 100 ppm, 50 ppm, 10 ppm. The LC50 value was obtained from the number of larvae that died after 24 hours of treatment with probit analysis.The results showed that the combination of cardamom extract and curcuma had a highly toxic level against Artemia salina Leach larvae with an LC50 value of 12.98 ppm, and a combination of cardamom extract (Amomum compactum Soland. ex Maton) and galangal (Alpinia galanga L) had an LC50 of 18.08 ppm. The results showed that both combinations are highly toxic due to LC50 ≤ 30 ppm values.