A therapeutic potentiality and toxicity concern of nutrient plant Annona squamosa Linn.

Annona squamosa Linn.fruit is famous for its nutritional value with a long history of medicinal benefits due to the presence of many phytochemicals,including alkaloids,diterpenes,essential oil,phytopeptides,etc.Several studies envisaged that Annona squamosa possesses cytotoxic,diuretic,antiurolithiatic,antitumor,anti-psoriatic,antioxidant,and hepatoprotective properties.This plant is traditionally used for the treatment of wound infection,dysentery,seizure,tumors,fever,vomiting,parasitic infections,hypertension,thyroid,toothache,acne,heart disease,inflammation,diabetes,hair loss,dandruff,hemorrhage,maggot-infected sores,abortifacient,and cough.However,some chemical constituents isolated from the plant have shown specific toxic effects in human and animal models,such as acute oral toxic effects,genotoxic,neurotoxic,and ocular toxic.The plant has diverse pharmacological actions,the seeds of this plant possess a genotoxic effect but on the contrary,the bark of the plant shows genoprotective activity.A large number of ethnobotanical studies reported the seed of this plant is used to induce abortion in humans,but a scientific study carried out in pregnant rats reported aqueous seed extract of the plant did not interfere with reproductive performance.The presented review summarized the traditional uses,pharmacological,and toxicological activities of the isolated compounds from this plant.Additionally,some patents and commercial products related to Annona squamosa are also brought up in this article to explore its application which would attract the scientific community to search out its hidden side.

Transcription factor OsWRKY72 is involved in Cu/Cd toxicity by regulating lignin synthesis in rice

Maintenance of ion homeostasis in plant cells is an essential physiological requirement for sustainable growth,development,and yield of crops.Plants respond to high levels of heavy metals such as copper(Cu)and cadmium(Cd)to avoid irreversible damage at the structural,physiological and molecular levels.Our previous study found that rice germin-like proteins(OsGLPs)are a type of Cu-responsive proteins.The deletion of 10 tandem OsGLP genes on chromosome 8 led to more severe heavy metal toxicity in rice.In this study,we show that rice WRKY transcription factor OsWRKY72 negatively regulates OsGLP8-7transcription.Overexpression of OsWRKY72 weakens the Cu/Cd tolerance of rice when exposed to Cu and Cd.OsWRKY72 suppressed expression of OsGLP8-7 and lignin synthesis genes,resulting in reduced lignin polymerization and consequently lower lignin accumulation in cell walls,thereby increasing the Cu and Cd accumulation.In addition,OsWRKY53 bound to OsWRKY72 to alleviate the transcriptional inhibition of OsGLP8-7.These results revealed that OsWRKY72-OsGLP8-7 is an important module response of rice to heavy metal stress,and that transcription factor OsWRKY72 acts upstream of OsGLP8-7 to regulate Cu/Cd toxicity.

Acute Single and Joint Toxicity Effects of Deltamethrin and Lambda-cyhalothrin on Zebrafish(Danio rerio)

In this research,the single and combined toxicity effects of two commonly used pesticides,lambda-cyhalothrin and deltamethrin,were investigated on zebrafish at 20℃,with a weight of(1±0.1)g and a length of(3.5±0.35)cm.The study revealed that lambda-cyhalothrin exhibited higher toxicity compared to deltamethrin.Additionally,when used together,these pesticides showed significantly increased toxic effects on zebrafish.The 96-h LC 50 values were determined to be 3.059μg/L(confidence limits 0.077-0.351μg/L)for lambda-cyhalothrin and 1.304μg/L(confidence limits;0.046-0.228μg/L)for deltamethrin,both demonstrating a significant positive correlation(P<0.05).These results underscore the importance of regulating and managing pesticide use to safeguard aquatic organisms and uphold environmental sustainability.

5-Bromo-2'-deoxyuridine labeling:historical perspectives,factors infiuencing the detection,toxicity,and its implications in the neurogenesis

The halopyrimidine 5-bromo-2′-deoxyuridine(BrdU)is an exogenous marker of DNA synthesis.Since the introduction of monoclonal antibodies against BrdU,an increasing number of methodologies have been used for the immunodetection of this synthesized bromine-tagged base analogue into replicating DNA.BrdU labeling is widely used for identifying neuron precursors and following their fate during the embryonic,perinatal,and adult neurogenesis in a variety of vertebrate species including birds,reptiles,and mammals.Due to BrdU toxicity,its incorporation into replicating DNA presents adverse consequences on the generation,survival,and settled patterns of cells.This may lead to false results and misinterpretation in the identification of proliferative neuroblasts.In this review,I will indicate the detrimental effects of this nucleoside during the development of the central nervous system,as well as the reliability of BrdU labeling to detect proliferating neuroblasts.Moreover,it will show factors influencing BrdU immunodetection and the contribution of this nucleoside to the study of prenatal,perinatal,and adult neurogenesis.Human adult neurogenesis will also be discussed.It is my hope that this review serves as a reference for those researchers who focused on detecting cells that are in the synthetic phase of the cell cycle.

Eco-toxicity and health risk assessment of polycyclic aromatic hydrocarbons in surface sediments of Burullus Lake in Egypt

Polycyclic aromatic hydrocarbons(PAHs)are ubiquitous environmental contaminants of growing concern due to their potential ecological and human health risks.This study presents a comprehensive assessment of PAHs contamination in the surface sediments of Burullus Lake,a vital and second largest delta lake in Egypt.The aim was to evaluate the eco-toxicity and potential health risks associated with the presence of these compounds.Surface seven sediment samples were collected from various drains in the southern part of Burullus Lake.Soxhlet extraction method was employed to extract PAHs(16PAHs)from the sediment sample.Analytically,target compounds were located using HPLC.The results showed that samples contained PAHs levels ranging from 0.038×10^(-6)to 0.459×10^(-6),which is considered heavily polluted by the European standard for PAHs pollution.Additionally,there was no apparent source of PAHs in the ElKhashah drain or the Brinbal Canal,as HPLC found none of the compounds.The most prevalent compound in sediment samples along the study area was fluoranthene.The diagnostic indices in the present study indicated that the hydrocarbons in the region originated from pyrolytic and man-made sources along the drains of Burullus Lake.The principal component analysis(PCA)and diagnostic ratios revealed that coal combustion and pyrolytic sources were responsible for the PAHs contamination in the surface sediments.The non-carcinogenic risk(HI),which is the product of the HQs for the adult and child populations,respectively,was calculated.HI values under 1,therefore,demonstrated that they had no carcinogenic effects on human health.TEQs and MEQs in the sediments of Burullus Lake do not have a cancer-causing impact on people.For the safety of nearby wildlife,aquatic life,and people,all activities that raise petroleum hydrocarbon levels in Burullus Lake must be adequately regulated and controlled.According to the ecological risk assessment,there is little chance that PAHs will be found in the sediments of Burullus Lake.This study underscores the urgent need for effective pollution control measures and regular monitoring of PAHs levels in Burullus Lake sediments to protect the aquatic ecosystem and public health.It also highlights the importance of considering eco-toxicity and human health risks in integrated risk assessments of PAHs-contaminated environments.

Levisticum officinale extract protects against CCl4-induced hepatotoxicity through anti-inflammatory,anti-fibrotic,and antioxidant properties in rats

Objective:To investigate the hepatoprotective effects of Levisticum officinale extract on CCl4-induced hepatotoxicity.Methods:Different doses of Levisticum officinale extract were given orally to rats for 10 days,then rats received a single dose of CCl4(2.5 mL/kg,50%v/v in liquid paraffin).Biochemical and histopathological assays were performed to assess the effects of the extract on liver function and architecture.Moreover,antioxidant and oxidative markers as well as inflammatory and fibrotic indicators were measured.Results:Pretreatment with Levisticum officinale extract significantly mitigated CCl4-induced damage to liver structure,improved serum levels of alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,urea,total bilirubin,and total protein,enhanced glutathione content and superoxide dismutase and catalase activities in the liver,as well as decreased plasma and hepatic malondialdehyde levels.Immunohistochemical results demonstrated that the extract reduced Ki-67 andα-SMA expression and Masson’s trichrome staining revealed decreased liver collagen in rats treated with Levisticum officinale extract.Moreover,Levisticum officinale extract markedly decreased the gene expressions of TNF-α,IL-6,TGF-β1,MCP-1,and COX-2.Conclusions:Levisticum officinale extract exerts hepatoprotective effects on CCl4-induced hepatotoxicity through antioxidant,anti-inflammatory,and anti-fibrotic activities.

Quality-adjusted time without symptoms or toxicity analysis of haploidentical-related donor vs.identical sibling donor hematopoietic stem cell transplantation in acute myeloid leukemia

Objective:We aimed to compare the quality-adjusted time without symptoms or toxicity(Q-TWiST)in acute myeloid leukemia(AML)patients who received haploidentical-related donor(HID)and identical sibling donor(ISD)hematopoietic stem cell transplantation(HSCT).Methods:Five clinical health states were defined:toxicity(TOX),acute graft-versus-host disease(GVHD),chronic GVHD(cGVHD),time without symptoms and toxicity(TWiST)and relapse(REL).The equation used in this study was as follows:Q-TWiST=UTOX×TOX+UTWiST×TWiST+UREL×REL+UaGVHD×aGVHD+UcGVHD×cGVHD.Results:A total of 239 AML patients were enrolled.We established a mathematical model,i.e.,Q-TWiST HID HSCT>Q-TWiST ISD HSCT,to explore the range of utility coefficients satisfying the inequality.Based on the raw data,the utility coefficient is equivalent to the following inequality:10.57067UTOX-46.27733UREL+105.9374+3.388078UaGVHD-210.8198UcGVHD>0.The model showed that when UTOX,UREL,and UaGVHD were within the range of 0-1,as well as when UcGVHD was within the range of 0-0.569,the inequality Q-TWiST HID HSCT>Q-TWiST ISD HSCT was valid.According to the results of the ChiCTR1800016972 study,the median coefficients of TOX,acute GVHD(aGVHD),and cGVHD were 0.56(0.41-0.76),0.56(0.47-0.72),and 0.54(0.37-0.79),respectively.We selected a series of specific examples of the coefficients,i.e.,UTOX=0.5,UREL=0.05,UaGVHD-0.5,and UcGVHD-0.5.The Q-TWiST values of ISD and HID HSCT were 896 and 900 d,respectively(P=0.470).Conclusions:We first observed that Q-TWiST was comparable between AML patients receiving HID HSCT and those receiving ISD HSCT.

Antimicrobial Activities of Extracts of Macrosphyra longistyla against Gram-Positive Oral Biofilm-Formers from School Children in Southwestern Nigeria and Toxicity Studies Using Brine Shrimps

The world will benefit from more effective antimicrobial agents against oral conditions arising from the actions of biofilm forming bacteria. Also, information is lacking on the oral biofilm-forming bacterial diversity in Southwestern Nigeria. In this study, we isolate and characterize oral biofilm producing bacteria in the oral cavities of schoolchildren in Southwestern Nigeria. We also investigate the antimicrobial properties of Macrosphyra longistyla extracts against the biofilm-formers and the toxicity of potent extracts. Samples were obtained from 109 schoolchildren aged 4 - 14 years from Lagos, Oyo and Osun States. Agar well diffusion technique was used in the antimicrobial susceptibility testing. Toxicity testing was done using brine shrimps (Artemia salina). Biofilm-formers in this study are Klebsiella sp., Streptococcus sp., Staphylococcus sp., and Micrococcus sp. Ethanol leaf extracts had the highest activity against all biofilm-producing bacteria. Ethanol stem bark extract, which elicited activity against Klebsiella only, was found to be less toxic than the ethanol leaf extract. Staphylococcus showed >10 mm susceptibility to the ethanol and aqueous extracts of Macrosphyra longistyla. Streptococcus and Micrococcus were susceptible to the antimicrobial actions of the ethanolic leaf extracts. Although the ethanol extracts of the leaves had lower minimum inhibitory concentrations than the ethanol extracts of the stem bark, toxicity studies showed ethanol extracts of the stem-bark to be more toxic than the ethanol extracts of the leaves. In conclusion, ethanolic extracts of Macrosphyra longistyla show potential as sources of antimicrobials against gram-positive, oral biofilm-forming bacteria.

Changes in acute and late toxicity and patient-reported health-related quality of life following radiotherapy in women with breast cancer:A 1-year longitudinal study

Objective:The objective of this study was to investigate the frequency of acute and late toxicities,as well as changes in the quality of life(QOL)for breast cancer patients following radiotherapy(RT).Materials and Methods:A total of 108 breast cancer women were recruited for this prospective study.Data were collected at various intervals;prior to,and 1,3,6 months,and 1 year after radiation therapy.The primary outcomes were toxicity radiation therapy oncology group/European Organization for Research and Treatment of Cancer(EORTC)criteria.Our secondary outcome was QOL,measured using EORTC QLQ-C30 and Edmonton Symptom Assessment Scale.We employed Friedman’s two-way analysis to evaluate the changes in QOL over the course of 1 year.Results:The early toxicities that are most commonly experienced include pharyngeal,skin,and mucous membrane toxicity.Late toxicities frequently involve skin and submucosal toxicity.To measure patient functionality,all functional subscale scores except for the patient’s emotional state increased over time compared to pre-RT.Symptoms of the patients,which were included in the QOL symptom scale,decreased during the follow-up period,except for fatigue;however,changes in pain,insomnia,and loss of appetite did not significantly change.We identified the analogous symptom profiles in Edmonton.Although patients’overall health scores declined in the 1st and 3rd months after radiotherapy(RT),they rebounded at 6 and 12 months.Conclusion:For breast cancer patients,RT did not adversely affect functional capacity or exacerbate symptoms,but persistent fatigue did increase during the observation period.Health-care professionals ought to devise strategies to assist patients with skin toxicity and fatigue.

Skin Toxicity of Wufang Babu Ointment to Zebrafish

[Objectives]Using wild-type AB strain of zebrafish as experimental animal,this study investigated the damaging effect of Wufang Babu Ointment on skin cells,in order to evaluate the skin toxicity of Wufang Babu Ointment.[Methods]Wild-type AB strain of zebrafish with an age of 2 d were taken and fed in different concentrations of Wufang Babu Ointment solution for 24 h.The number of deaths in each group of zebrafish was recorded,and the mortality rate was calculated.Using Origin 8.0 software,the maximum non lethal concentration(MNLC)was simulated.Zebrafish raised in different concentrations of Wufang Babu Ointment solution for 24 h were placed under an anatomical microscope for taking photos,to analyze and calculate the incidence of skin damage in zebrafish.Based on the statistical analysis results of this indicator,the skin toxicity of Wufang Babu Ointment was evaluated.[Results]The MNLC of Wufang Babu Ointment on zebrafish was 671μg/mL;Wufang Babu Ointment can induce skin damage at the concentrations of 224μg/mL(1/3 MNLC)and 671μg/mL(MNLC).[Conclusions]Wufang Babu Ointment had certain skin toxicity to zebrafish.

Acute Toxicity of Jinchuan Formula Plum Wine Extract and Its Protective Effect on Mice with Liver Injury

[Objectives]To investigate the acute toxicity and hepatoprotective effect of Jinchuan formula plum wine extract on mice,determine its safety range,and evaluate its hepatoprotective effect.[Methods]The median lethal dose(LD_(50))was determined by acute toxicity test with the toxic reaction and mortality of mice as indexes.Sixty Kunming mice were randomly divided into 6 groups:normal control group,model group(ConA-induced liver injury model),Jinchuan formula plum wine high,medium and low dose groups(1.0,0.5,0.25 g/kg)and silybin group(0.1 g/kg).The levels of ALT,AST,LDH in serum and TG,VLDL in liver were measured.After HE staining,the pathological changes of liver tissue in mice were observed,and the liver protective effect of Jinchuan formula plum wine extract was analyzed and evaluated.[Results]LD_(50)was 11.18 g/kg,and the 95%confidence limit of LD_(50)was 10.31-12.05 g/kg.The high-dose group of Jinchuan formula plum wine extract could significantly reduce the serum ALT and AST activities of ConA-induced liver injury mice(P<0.05).[Conclusions]Jinchuan formula plum wine extract is relatively safe,and also has a protective effect on liver injury.

Toxicity Evaluation of Different Exposure Scenarios of Road Dust Using Daphnia magna and Artemia salina as Aquatic Organisms, and Prosopis cineraria and Vachellia tortilis as Native Plant Species

Particulate matter (PM10) deposited as road dust is considered an important source of contamination from atmosphere. However, there are limited studies on the toxicity of road dust as such on different organisms. This study evaluates the toxicity of road dust using different extraction scenarios on Daphnia magna and Artemia salina as aquatic organisms and also on Prosopis cineraria and Vachellia tortilis as local plant species. Chemical analysis of different extracts shows considerable amount of trace metals, however the trace metals in the dust extract associated with suspended sediment were not absorbed by the receptors. On the other hand, the concentration of trace metals in the artificial mixture was found bioavailable and absorbed causing a high percentage of mortality. In the plant assay, significant difference was obtained in the germination percentage between the control and three different extraction exposures in both plant species. The mean root length of P. cineraria and V. tortilis were higher in 20% and 50% extracts than the control probably due to the availability of nutrients from the dust extract. Interestingly however, the seedling vigor index was the opposite with higher index in the control and lower in dust extracts that contain heavy metals.

Development and Application of Procedures for the Management of Skin Toxicity Related to Immune Checkpoint Inhibitors in Patients with Lung Cancer

Objective: To establish the procedures for the management of skin toxicity related to immune checkpoint inhibitors in patients with lung cancer and explore the effect of application. Methods: A total of 24 evidence-based evidences were collected from 7 aspects, including risk factors, baseline screening, ICIs monitoring, daily skin care, multidisciplinary management, symptom management and health education. A total of 157 lung cancer patients and 94 nurses from 8 wards of the Oncology department of our hospital from November 2022 to May 2023 were selected by convenience sampling. A total of 77 patients and 46 nurses from ward 1 - 4 were divided into the baseline group. There were 80 patients and 48 nurses in Ward 5 - 8 as the evidence-based practice group. In the baseline group, patients were treated with routine methods such as assessing skin symptoms, taking medication according to symptoms, guiding to keep skin clean and moist, eating a light diet, and avoiding scratching. The evidence-based practice group adopts an evidence-based continuous improvement model for nursing. The differences in the severity of symptoms of skin toxicity in the second cycle of medication and the knowledge and practice of self-care of skin toxicity were compared between the two groups before and after the use of the syndrome, as well as the differences in the implementation rate of review indicators, evidence-based ability and knowledge and practice of skin toxicity care before and after the use of the syndrome. Results: The incidence and severity of cutaneous toxicity were significantly lower after treatment than before treatment (P P < 0.05). Conclusion: The implementation of immune checkpoint inhibitor-related skin toxicity management procedures can effectively reduce the incidence and severity of skin toxicity symptoms, optimize the clinical pathway, and improve the quality of care.

Evidence-Based Nursing Practice of Reducing Immune-Related Skin Toxicity of Tumor Patients Guided by Sensitive Indicators

Purpose research on nursing sensitive indicators in tumor Patients application effect in immune-related skin toxicity management. Method select our hospital April to June, 202360 cases patients with immune therapy settings as the control group. August-October, 2023 60 cases the patients treated with immune therapy were the experimental group. The control group adopted regular nursing methods, while the experimental group sensitive Indicators, evidence-based give preventive care. The social situation, psychological state, physical function, quality of life score, incidence of skin toxicity caused by immune checkpoint inhibitors, moderate and above of the two groups of patients were compared. Incidence of skin toxicity. Result: experience group SAS score, SDS score higher than the control group, the difference was statistically significant (P < 0.05);The incidence of skin toxic reactions caused by immune checkpoint inhibitors and the incidence of moderate and above skin toxic reactions in the experimental group are lower than those in the control group, and the difference is statistically significant (P < 0.05). Conclusion: sensitive indicator guidance evidence-based preventive care can reduce the degree of immune-related skin toxicity, improve the psychological state and quality of life of tumor patients treated with immune therapy and reduce the incidence of adverse reactions, improve nursing quality and patient satisfaction.

Determination of the Mineral Composition of the Pulp and Evaluation of the Acute Toxicity of the Seeds of Carica papaya L. Consumed in Lubumbashi and Kinshasa in the Democratic Republic of the Congo

This work aimed, on the one hand, to determine the mineral and phytochemical composition of Carica papaya in order to guarantee the food safety of consumers and on the other hand, to evaluate the acute toxicity of papaya seeds. The papayas were bought at the Mzée market in Lubumbashi and Selembao in Kinshasa. Fruit sampling was done according to the ISO 7002 standard on agricultural and food products;the papayas were firm, mature, and without stains or physical damage. The analysis results of the papaya pulp showed both for the samples from the city of Lubumbashi and for the city province of Kinshasa that it contains respectively 85.87% and 84.46% water, 0.59% and 0.53% ash content. The mineral evaluation of our two samples presented a potassium content of 200 ± 8 mg, magnesium 13.12 ± 3 mg, calcium 22.15 ± 2 mg, sodium 3 mg ± 0.5 for the sample from Lubumbashi and 192.32 ± 8 mg of potassium, 14.458 ± 3 mg of magnesium, 20.58 ± 2 mg of calcium and 3.58 ± 0.5 mg of sodium for the sample from Kinshasa in macroelements. Concerning the trace elements, after analysis, we found zinc content (0.29 ± 0.1 mg and 0.12 ± 0.1 mg), copper (0.02 ± 0.01 mg and 0.14 ± 0.01 mg), and iron (2.22 ± 0.5 mg and 2.04 ± 0.5 mg) respectively for Lubumbashi and Kinshasa. The chemical screening indicates the presence of alkaloids, saponosides, tannins catechics, flavonoids and anthocyanins in the palm wine and ethanolic extract of the seeds of Carica papaya and an absence of cyanogenic glycosides and gallic tannins. With mild toxicity, the seeds of the fruit of Carica papaya L. can be used with moderate risk by the population.

Improvement of Rice Plant Root by Kaolin Application in Iron Toxicity Condition at Zoukougbeu (Central-West of Côte d’Ivoire)

In the tropics, lowland rice cultivation is often confronted with the problem of iron toxicity. The solution proposed by research in general is the use of industrial silicon. However, the high cost of industrial silicon limits its adoption by farmers. A study was carried out in Zakogbeu;Center-West of Côte d’Ivoire, to assess the potential of kaolin to mitigate the effect of this soil constraint on the root of the rice plant. Five kaolin-based treatments were analyzed (T0 = 0 kg kaolin ha−1, T1 = 366 kg kaolin ha−1, T2 = 736 kg kaolin ha−1, T3 = 1097 kg kaolin ha−1 and T4 = 1465 kg kaolin ha−1 are 0, 200, 400, 600 and 800 kg SiO2 ha−1) in a device in complete random blocks, with 5 repetitions. The results obtained show that kaolin supply increases the length of the root tissue as well as the number of branching of the root of the rice plant. Root tissue increased from 10 cm with T0 treatment to more than 15 cm with treatment T4. The microscopic observation of the roots shows that in the treatment T0, the roots present only primary ramifications and the tertiary and quaternary ramifications are observed with the treatments T3 and T4. The contribution of kaolin is an alternative to inhibit the effect of iron toxicity on the rice plant root development in iron toxicity condition.

Reflections on the Toxicity and Safety of Traditional Chinese Medicine Combined with the Cases of Nephrotoxicity and Hepatotoxicity

This paper analyzes the relationship between toxicity and safety of traditional Chinese medicine(TCM)based on the cases of current nephrotoxicity and hepatotoxicity,and summarizes the literature on hepatotoxicity and nephrotoxicity.It is found that the main reasons for the toxic reaction of TCM are own factors of drugs,irregular administration of medicine and individual difference.However,as long as the"quality"and"quantity"of TCM are guaranteed,the toxicity of TCM can be controlled within the safety range.

Phytochemical composition and toxicity assessment of Ammi majus L.

Objective:To assess the acute and subacute toxicity as well as the phytochemical composition of two extracts and three fractions of Ammi majus L.Methods:The aqueous extracts were prepared separately by maceration for 48 h and by infusion for 1 h,while the fractions were prepared by the Soxhlet extractor,successively employing cyclohexane,ethyl acetate,and ethanol.The acute toxicity study was carried out in accordance with the OECD N°423 guideline at a single dose(2000 mg/kg)in mice for 14 days.The subacute toxicity study was performed by a daily oral administration of 250 mg/kg 2 for 10 d and 100 mg/kg doses for 28 d.Phytochemical screening was performed using staining and precipitation reactions,while the chemical characterization of some analytes was detected by HPLC-MS/MS analysis.Results:In the acute toxicity study,no signs of toxicity such as convulsion,salivation,diarrhea,sleep and coma were observed during 30 minutes and 14 days,so the lethal dose was higher than 2000 mg/kg for each extract and fraction.The subacute toxicity results showed that at a dose of 250 mg/kg,61.10%of the animals died and the rest developed morbidity.On the other hand,at a dose of 100 mg/kg,all the animals were still alive after 28 days,with no morbidity and the biochemical parameters were normal with no abnormalities in the liver,kidneys and pancreas.Phytochemical screening indicated the presence of flavonoids,tannins,coumarins,and free quinones and the absence of alkaloids and anthocyanins.Conclusions:The extracts and fractions of Ammi majus L.are not toxic in the short and long term with a varied chemical composition.Toxicological tests on animals other than rodents and in the long term(more than 28 days)are needed to further confirm the safety of Ammi majus extracts.

Essential tremor:A three-dimensional neurosphere in vitro model to assess the neurotoxicity of harmane

Objectives: To use a novel in vitro model of three-dimensional(3D) neurosphere cultures to assess neurotoxic or neuroprotective effects with harmane as a model compound.Methods: A reproducible model of 3D spheroids was developed from embryonic mouse cortical neurons,using molded agarose micro-wells;this method seems particularly practical as it is customizable and widely available and does not require specific cell treatments or assay components different from 2D cultures, allowing for the easy transposition of routine protocols. To assess the neurotoxic effects of harmane, a resazurin assay was performed to measure cell viability, and a highly sensitive fluorometric method, based on the oxidation of dichlorodihydrofluorescein, was applied to measure eventually induced reactive oxygen species(ROS) after exposure to harmane at increasing concentrations of 50 100,and 250 μm.Results: Hydrogel microwells facilitated the assembly of spheroids containing neurons and glial cells into a complex 3D structure and prevented the agglomeration of spheroids. Exposure to harmane induced cytotoxicity in 3D neural spheroids, which was correlated with harmane concentrations, with a 27%reduction in viability at 250 μm. Harmane that did not induce significant levels of oxidative stress was detected for all tested concentrations.Conclusion: This 3D neurosphere model mimics a neuronal microenvironment, allowing a fine study of neurodegenerative disorders and the effects of chemicals on the brain. This model opens novel opportunities, not only from a pathogenetic point of view but also from a therapeutic perspective.

Acute and Sub-Chronic Toxicity Evaluation of the Crude Methanolic Bark Extract of Bridelia micrantha (Hochst.) Baill. (Phyllanthaceae) and Its Fraction

Bridelia micrantha, commonly known as coastal golden leaf, is a member of the family Phyllanthaceae. In preliminary studies nine fractions, named F1 - F9, were obtained by fractionating the crude methanol extract of the stem bark of Bridelia micrantha using column chromatographic techniques. The fraction F6 was the most active when tested for antibacterial activity. Thus, toxicity of this fraction was investigated for further use. The present study evaluated the acute and sub-chronic toxicity of the crude methanolic bark extract of Bridelia micrantha and its fraction. The acute toxicity was carried out according to the experimental protocol of Organization for Economic Co-operation and Development (OECD). The plant extract or the fraction F6 was administered orally to female mice at a single dose of 2000 mg/kg and the animals were observed for any behavioral changes or mortality for 14 days. In the sub-chronic toxicity study, the extract and fraction were administered orally at 200, 400 and 800 mg/kg bw/day for 28 days to healthy Wistar rats. The general behavior and body weight of the rats were recorded daily. At the end of the experimental period, hematological and biochemical analyses, changes in vital organ weight (liver, lung, heart, spleen and kidney), and histopathological examination of the liver and kidney were performed. No mortality or adverse effects were noted at the 2000 mg/kg dose during the oral acute toxicity test. In the sub-chronic study, the crude methanolic bark extract of Bridelia micrantha and the fraction F6 induced no mortality or treatment-related adverse effects on body weight, general behavior, relative organ weights, hematological and biochemical parameters. Histopathological examination of the liver and kidney showed normal architecture suggesting no morphological alterations. In conclusion, the oral administration of the crude methanolic bark extract of Bridelia micrantha and the fraction F6 for 28 days at a dosage of up to 800 mg/kg did not induce toxicological damage in rats. From acute toxicity study, the median lethal dose (LD50) of the crude methanolic bark extract of Bridelia micrantha and the fraction F6 was estimated to be more than 2000 mg/kg.