Long-term Toxicity of Maxing Erchen Zhike Granules

[Objectives]To study the long-term toxicity of Maxing Erchen Zhike granules to rats after intragastric administration,so as to provide reference for its preclinical safety evaluation.[Methods]Total 80 rats were randomly and evenly divided into high-dose group(1.2 mL/100 g,120 g/kg),middle-dose group(96.0 g/kg),low-dose group(72.0 g/kg)and blank control group.The rats in the treatment groups were administered with corresponding doses of Maxing Erchen Zhike granules,and those in the blank control group were given with equal-amount normal saline.The administration lasted for 30 consecutive days.During the experiment,the rats'feed intake,activity,feces and other conditions and toxicity reactions were observed every day.After 24 h of the last administration,12 rats(half male and half female)were randomly selected from each group.Each of the rats was anesthetized with 10%chloral hydrate solution(0.3 mL/100 g)through intraperitoneal injection and subjected to abdominal aorta blood collection(two tubes)for hematological examination and blood biochemical examination(serum).Then,the main organs of the rats were weighed,and pathological examinations were performed.After that,the main organs were weighed and pathological examination was performed.The remaining rats in each group were discontinued and observed for 14 d.On the 15th d,they were subjected to the same treatment,and the body weight,organ coefficients,hematological indices,blood biochemical indices and pathological indices were examined.[Results]After 30 d of administration,there was no abnormality in the appearance and behavior of the animals.There was no significant difference in the daily consumption of feed among the groups,and there was no special case of weight gain.Among the blood biochemical indices,the ALB and ALT levels of each administration group were significantly different from those of the blank control group(P<0.05).The results of histopathological examination show that there was one case of interstitial pneumonia in each of the high-dose group,middle-dose group and blank control group.After 14 d that the administration was stopped,one case of focal myocarditis appeared in the high-dose group,and one case of interstitial pneumonia appeared in the middle-dose group.[Conclusions]Maxing Erchen Zhike granules are safe to be administered to rats at 100 times the clinical dose.and there should be no safety hazards clinically when used at conventional doses.

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.

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.

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.

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.

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.

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.

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.

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.

2022 Chinese expert consensus and guidelines on clinical management of toxicity in anti-CD19 chimeric antigen receptor T-cell therapy for B-cell non-Hodgkin lymphoma

Adoptive cellular immunotherapy with chimeric antigen receptor(CAR)T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma(B-NHL).With increasing approval of CAR T-cell products and advances in CAR T cell therapy,CAR T cells are expected to be used in a growing number of cases.However,CAR T-cell-associated toxicities can be severe or even fatal,thus compromising the survival benefit from this therapy.Standardizing and studying the clinical management of these toxicities are imperative.In contrast to other hematological malignancies,such as acute lymphoblastic leukemia and multiple myeloma,anti-CD19 CAR T-cell-associated toxicities in B-NHL have several distinctive features,most notably local cytokine-release syndrome(CRS).However,previously published guidelines have provided few specific recommendations for the grading and management of toxicities associated with CAR T-cell treatment for B-NHL.Consequently,we developed this consensus for the prevention,recognition,and management of these toxicities,on the basis of published literature regarding the management of anti-CD19 CAR T-cell-associated toxicities and the clinical experience of multiple Chinese institutions.This consensus refines a grading system and classification of CRS in B-NHL and corresponding measures for CRS management,and delineates comprehensive principles and exploratory recommendations for managing anti-CD19 CAR T-cell-associated toxicities in addition to CRS.

Toxicity and horizontal transfer of bifenthrin and dimefluthrin against the red imported fire ant, Solenopsis invicta Buren(Hymenoptera: Formicidae), and the efficacy of their dust applications in the field

The red imported fire ant,Solenopsis invicta Buren,poses a significant threat to biodiversity,agriculture,and public health in its introduced ranges.While chemicals such as toxic baits and dust are the main methods for S.invicta control,toxic baits are slow,requiring approximately one or two weeks,but dust can eliminate the colony of fire ants rapidly in just three to five days.To explore more active ingredients for fire ant control using dusts,the toxicity of bifenthrin and dimefluthrin,the horizontal transfer of bifenthrin and dimefluthrin dust and their efficacy in the field were tested.The results showed that the LD50(lethal dose) values of bifenthrin and dimefluthrin were 3.40 and 1.57 ng/ant,respectively.The KT50(median knockdown time) and KT95(95%knockdown time) values of a 20μg mL^(–1)bifenthrin dose were 7.179and 16.611 min,respectively.The KT50and KT95of a 5μg mL^(–1)dimefluthrin dose were 1.538 and 2.825 min,respectively.The horizontal transfers of bifenthrin and dimefluthrin among workers were effective.The mortality of recipients (secondary mortality) and secondary recipients (tertiary mortality) were both over 80%at 48 h after 0.25,0.50 and 1.00%bifenthrin dust treatments.The secondary mortality of recipients was over 99%at 48 h after 0.25,0.50 and 1.00% dimefluthrin dust treatments,but the tertiary mortality was below 20%.The field trial results showed that both bifenthrin and dimefluthrin exhibited excellent fire ant control effects,and the comprehensive control effects of 1.00%bifenthrin and dimefluthrin dusts at 14 d post-treatment were 95.87 and 85.70%,respectively.

Differential Expression of Iron Deficiency Responsive Rice Genes under Low Phosphorus and Iron Toxicity Conditions and Association of OsIRO3 with Yield in Acidic Soils

With the hypothesis that iron(Fe) deficiency responsive genes may play a role in Fe toxicity conditions,we studied five such genes OsNAS1,OsNAS3,OsIRO2,OsIRO3 and OsYSL16 across six contrasting rice genotypes for expression under high Fe and low phosphorus(P) conditions,and sequence polymorphism.Genotypes Sahbhagi Dhan,Chakhao Poirieton and Shasharang were high yielders with no bronzing symptom visible under Fe toxic field conditions,and BAM350 and BAM811 were low yielders but did not show bronzing symptoms.Hydroponic screening revealed that the number of crown roots and root length can be traits for consideration for identifying Fe toxicity tolerance in rice genotypes.Fe contents in rice roots and shoots of a high-yielding genotype KMR3 showing leaf bronzing were significantly high.In response to 24 h high Fe stress,the expression levels of OsNAS3 were up-regulated in all genotypes except KMR3.In response to 48 h high Fe stress,the expression levels of OsNAS1 were3-fold higher in tolerant Shasharang,whereas in KMR3,it was significantly down-regulated.Even in response to 7 d excess Fe stress,the transcript abundances of OsIRO2 and OsNAS3 were contrasting in genotypes Shasharang and KMR3.This suggested that the reported Fe deficiency genes had a role in Fe toxicity and that in genotype KMR3 under excess Fe stress,there was disruption of metal homeostasis.Under the 48 h low P conditions,OsIRO2 and OsYSL16 were significantly up-regulated in Fe tolerant genotype Shasharang and in low P tolerant genotype Chakhao Poirieton,respectively.In silico sequence analysis across 3 024 rice genotypes revealed polymorphism for 4 genes.Sequencing across OsIRO3and OsNAS3 revealed nucleotide polymorphism between tolerant and susceptible genotypes for Fe toxicity.Non-synonymous single nucleotide polymorphisms and insertion/deletions(InDels) differing in tolerant and susceptible genotypes were identified.A marker targeting 25-bp InDel in OsIRO3,when run on a diverse panel of 43 rice genotypes and a biparental population,was associated with superior performance for yield under acidic lowland field conditions.This study highlights the potential of one of the vital genes involved in Fe homeostasis as a genic target for improving rice yield in acidic soils.

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.

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.

Evaluation of the Nutritional Value and Acute Toxicity of the Seeds of the Fruit of Annona muricata L. (Sursop) Consumed in Kinshasa

In this paper, the author aimed to determine the nutritional value of soursop (Annona muricata L. fruit) consumed in Kinshasa as well as the study of the acute toxicity of its seeds. The fruit of Annona muricata L. was sampled according to the ISO 7002 standard for agricultural and food products. The selected fruits were ripe, without physical damage. The usual analytical methods allowed the determination of the nutritional value of the fruit pulp of Annona muricata L. The water content was measured by the method of loss of mass on drying. The total amount of ash was determined by incineration in the oven at 550°C. The mineral elements were determined by inductively coupled plasma spectrometry (ICP0). The determination of acute toxicity was carried out on 25 female mice of the NMRI SUISSE species according to OECD 425 guidelines. For 100 grams of fresh material from the fruit pulp, we noted a very high water content of 84% ± 6%. We also note a particularly high amount of carbohydrates with a rate of 12.2% ± 2%. Protein and lipid content were relatively low at 1% ± 0.01% and 0.7% ± 0.3% respectively. The dietary fiber content was 0.8% ± 0.2%. An energy value of 49.3 Kcal per 100 grams of pulp was determined. The LD 50 obtained was 3320 mg/kg, indicating slight toxicity of soursop seeds. The results of this study show that the white pulp of the fruit of Annona muricata L. consumed in Kinshasa is rich in carbohydrates when we compare it to others biomolecules. It also contains dietary fiber and mineral salts making soursop an excellent constituent of a weight loss diet with a low energy intake.

Toxicity and Molecular Mechanisms of Actions of Silver Nanoparticles

Silver nanoparticles (AgNPs) have gained popularity due to their antibacterial properties, and are therefore widely used in several applications such as wound dressings, food packaging, and water purification. However, the toxicity of AgNPs to humans and the environment is a growing concern. This review aims to summarize the current knowledge on the toxicity and molecular mechanisms of action of AgNPs. The toxicity of AgNPs can be attributed to their small size, which allows them to enter cells and interact with cellular components. Reports suggest that AgNPs can induce cell death, DNA damage, and oxidative stress in various cell types. The toxic effects of AgNPs differ based on their size, shape, surface charge, and coating. The molecular mechanisms behind the toxicity of AgNPs involve the production of reactive oxygen species, disruption of cellular membranes, and activation of proinflammatory cytokines. Overall, the toxicity of AgNPs is dependent on various factors, and more research is needed to fully understand the mechanisms behind their toxicity. This review highlights the need for proper risk assessments and regulations to minimize the adverse effects of AgNPs on human health and the environment.

A single-cell landscape of triptolide-associated testicular toxicity in mice

Triptolide is a key active component of the widely used traditional Chinese herb medicine Tripterygium wilfordii Hook.F.Although triptolide exerts multiple biological activities and shows promising efficacy in treating inflammatory-related diseases,its well-known safety issues,especially reproductive toxicity has aroused concerns.However,a comprehensive dissection of triptolide-associated testicular toxicity at single cell resolution is still lacking.Here,we observed testicular toxicity after 14 days of triptolide exposure,and then constructed a single-cell transcriptome map of 59,127 cells in mouse testes upon triptolide-treatment.We identified triptolide-associated shared and cell-type specific differentially expressed genes,enriched pathways,and ligand-receptor pairs in different cell types of mouse testes.In addition to the loss of germ cells,our results revealed increased macrophages and the inflammatory response in triptolide-treated mouse testes,suggesting a critical role of inflammation in triptolide-induced testicular injury.We also found increased reactive oxygen species(ROS)signaling and downregulated pathways associated with spermatid development in somatic cells,especially Leydig and Sertoli cells,in triptolide-treated mice,indicating that dysregulation of these signaling pathways may contribute to triptolide-induced testicular toxicity.Overall,our high-resolution single-cell landscape offers comprehensive information regarding triptolide-associated gene expression profiles in major cell types of mouse testes at single cell resolution,providing an invaluable resource for understanding the underlying mechanism of triptolide-associated testicular injury and additional discoveries of therapeutic targets of triptolide-induced male reproductive toxicity.

Assessment of Nephro-, Hepato-, and Sex-Dependent Toxicity of Carmoisine Exposure in Albino Rats

Aim: To evaluate chronic exposure of carmoisine at ADI doses on some hepatocellular and renal parameters of male and female albino rats as well as to determine sex-dependent toxicity. Study Design: The study involves treatment for 30, 60, and 90 days. Each phase consists of 40 rats, divided into treatment and control groups. The treated groups were orally administered with 4.0 mg/kg of carmoisine daily for the periods of 30, 60, and 90 days. Methodology: At the end of the treatment, the rats were allowed to fast for 18 hours followed by the collection of 5 ml of whole blood specimens by means of cardiac puncture into Lithium Heparin bottles and fluoride oxalate bottles (for glucose only). Plasma obtained was analyzed for glucose (GLU), AST, ALT, ALP, creatinine (CRT), and urea. Hepatic and Renal tissues collected were fixed in 10% formol saline and later examined histologically using H&E stain. Statistical data analysis was done using GraphPad Prism version 9.02. Results: Glucose indicated significant increases after 30, 60, and 90 days of chronic treatment at ADI doses. Urea, Creatinine, AST, ALT and ALP showed significantly higher values after 60 and 90 days of treatment (except creatinine in male rats and ALP in female rats after 60 and 90 days respectively). Hepatic distortions, vacuolation, compression of central vein were seen in the liver section while distortion of proximal and distal tubules, and inflammation of the glomerulus were observed in the renal tissue of the treated rats. Conclusion: The administration of camoisine over a period of 30 days at ADI dose did not indicate hepatocellullar and renal derangements as well histological distortions in liver, and kidneys. However, after 60 and 90 days, mild hepatocellular, and renal derangements were seen. No sex-dependent toxicity was observed.

Prevalence of Acute Myocardial and Brain Toxicity in Emergency Department Patients Exposed to Carbon Monoxide

Introduction: Due to its severe toxicity, carbon monoxide poisoning is an emergency that leads to cardiac and brain involvement, and emergency physicians should aim to master this diagnosis. This study is intended to describe the expected prevalence of these severe toxicities in the emergency department. Materials and Methods: A retrospective cohort of consecutive patients over 16 years of age presenting with carbon monoxide poisoning to the emergency department of the Hospital Universitario Austral, Argentina, during the period from January 2018 to June 2022. The prevalence of myocardial and brain toxicity was assessed regarding percentage, continuous variables with mean and standard deviation, categorical variables with percentage and absolute frequency. Positive findings of acute neurological toxicity included seizures, syncope and coma, while cardiovascular toxicity encompassed acute myocardial infarction (MI) diagnosed by electrocardiogram or elevated troponin levels, arrhythmias, and the development of pulmonary edema/ congestive heart failure (CHF) confirmed by chest X-ray with suggestive signs or clinically compatible symptoms. Patients were followed-up for 90 days to estimate hospitalization and mortality. Results: A total of 67 patients were evaluated;44.77% of them were males with a mean age of 38.5 ± 14.97 years. The prevalence of acute myocardial toxicity was 7.46% (n: 5). Among these patients, 3 had overweight as a risk factor, and 3 showed ECG abnormalities with negative T-waves. The prevalence of acute brain toxicity was 8.9% (n: 6). In total, 37% (n: 25) of patients met the criteria for hyperbaric oxygen therapy, of which 32% (n: 8) underwent more than one session. A total of 7.46% of patients (n: 5) required hospitalization. Mortality at 90 days was 0%. Conclusion: Among the patients who presented to the emergency department, the prevalence of acute myocardial toxicity was 7.46% (n: 5), which is lower than the prevalence reported in other studies to date. The prevalence of acute brain toxicity was 8.9% (n: 6), and there are no studies describing the prevalence of acute brain toxicity in the emergency department to date. There were no fatalities in our series.

Plant-derived natural compounds in the treatment of arsenic-induced toxicity

Arsenic toxicity,imposed mainly by arsenic-contaminated groundwater,is considered a critical threat to global communal health,as there is no specific and proven conventional therapy for chronic arsenic toxicity,i.e.,arsenicosis,which is an insidious global public health menace affecting 50 countries.Alternative options should,therefore,be explored for the mitigation of arsenicosis.Literature survey reveals several natural compounds from plants possess significant protective efficacy against arsenic toxicity in chiefly preclinical and few clinical investigations.The studies on the ameliorative effects of plant-derived natural compounds against arsenic toxicity published in the last 25 years are collated.Forty-eight plant-based natural compounds possess alleviative effects on experimental arsenic-induced toxicity in animals,six of which have been reported to be clinically effective in humans.A potential nutraceutical or therapeutic candidate against arsenicosis for humans may thus be developed with the help of recent advancements in research in this area,along with the currently available treatments.