Food and Chemical Toxicology最新文献

{"title":"A 90-day oral toxicity study evaluation of azaphilone derived from Talaromyces amestolkiae: A natural food colorant.","authors":"Talita Cristina Mena Segato, Erika Leão Ajala Caetano, Rafaella de Barros Mott, Natasha Lien de Almeida Ibanez, Camila da Cunha Frattes, Caio de Azevedo Lima, Mônica Rodrigues Alves, Valéria Carvalho Santos-Ebinuma, Denise Grotto","doi":"10.1016/j.fct.2025.115394","DOIUrl":"10.1016/j.fct.2025.115394","url":null,"abstract":"<p><p>Colorants are widely used in the food industry, especially artificial ones, due to their practicality and low cost. However, some artificial colorants can be harmful to human health. In order to substitute the artificial sources, some microorganisms such as fungi has been highlighted for its production and variety of colorants. The fungus Talaromyces amestolkiae is capable of producing, through its metabolism, colorants classified as azaphilone compounds. The objective of this work was study the sub-chronic (90-day oral) safety evaluation of the novel azaphilone colorant produced by T. amestolkiae in male and female Wistar rats. After a preliminary acute toxicity test, the animals were treated with doses of 250, 500 and 1000 mg/kg body weight via gavage for 90 days. Hematological and biochemical parameters as well as histological examinations were carried out. Oxidative stress was also assessed. Liver damage was observed through an increase in ALT and ALP and confirmed with histological analysis and renal alterations were identified by increased sodium levels and confirmed through histological examination in highest doses, both possibly caused by compounds from the culture medium. Lipid dysregulation, including an increase in triglycerides, was observed at the highest concentrations. Alterations in the Purkinje cells were observed, probably as a consequence of oxidative stress caused by the colorant, but the brain tissue was unaltered. The findings of this study show that the extract containing azaphilone colorants at concentrations higher than 500 mg/mL poses challenges for safe application in food products. However, since the amount of colorant used as a food additive is typically low and tailored to the target color, these results indicate that the extract obtained after cultivation should undergo extraction and purification steps. The dose of 250 mg/kg/bw proved to be safe for both male and female rats, with no or few adverse effects observed.</p>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"115394"},"PeriodicalIF":3.9,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sinomenine synergistically enhances 5-Fu anticancer effects in oral cancer through modulating the miR-140-5p-PDK1-anaerobic glycolysis pathway","authors":"Dongmei Wang ,&nbsp;Rui Wang ,&nbsp;Hui Sun ,&nbsp;Zhi Wen","doi":"10.1016/j.fct.2025.115385","DOIUrl":"10.1016/j.fct.2025.115385","url":null,"abstract":"<div><div>Oral squamous cell carcinoma (OSCC) is a type of human malignancy with a high mortality rate worldwide. Sinomenine (SIN), an active component of sinomenium acutum, has shown potential antitumor activities in various types of cancers. This study discovered that the combination of 5-Fu and SIN treatments had synergistic inhibitory effects on OSCC cells (CI &lt; 1). Moreover, miRNA-140-5p was significantly downregulated in OSCC tumors and cell lines. Treatment with sinomenine upregulated miR-140-5p and suppressed anaerobic glycolysis of OSCC cells. We established a 5-Fu resistant OSCC cell line (CAL33 5-Fu R), which showed elevated anaerobic glycolysis and downregulated miR-140-5p. Through western blot, luciferase assay, and rescue experiments, we identified the pyruvate dehydrogenase kinase 1 (PDK1), a key enzyme in anaerobic glycolysis, as a direct target of miR-140-5p, overexpression of which led to anaerobic glycolysis suppression and 5-Fu sensitization in OSCC cells. Furthermore, blocking the SIN-induced miR-140-5p successfully overcame the SIN-inhibited anaerobic glycolysis and 5-Fu resistance in OSCC cells. Meaningfully, results from <em>in vivo</em> mice xenograft experiments validated that sinomenine enhanced anti-cancer effects of 5-Fu treatment. Our findings reveal that the combination of sinomenine and 5-Fu synergistically enhances the cytotoxicity of OSCC cells by regulating the miR-140-5p-PDK1 axis.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"200 ","pages":"Article 115385"},"PeriodicalIF":3.9,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sildenafil abrogates radiation-induced hepatotoxicity in animal model: The impact of NF-κB-p65, P53, Nrf2, and SIRT 1 pathway","authors":"Waleed A.I. Khallaf ,&nbsp;Abd Elmoneim A.H. Taha ,&nbsp;Ahmed S. Ahmed ,&nbsp;Mohamed I.A. Hassan ,&nbsp;Amira M. Abo-youssef ,&nbsp;Ramadan A.M. Hemeida","doi":"10.1016/j.fct.2025.115373","DOIUrl":"10.1016/j.fct.2025.115373","url":null,"abstract":"<div><div>Ionizing radiation has both beneficial and harmful effects on human health, prompting researchers to find ways to protect organs from its adverse impacts. Sildenafil (SIL) has gained attention in protective medicine due to its antioxidant, anti-inflammatory, and anti-apoptotic properties.</div></div><div><h3>Aim</h3><div>This study aimed to investigate SIL's protective mechanisms against radiation-induced liver damage.</div></div><div><h3>Method</h3><div>Forty adult male Wistar rats were divided into: control group, SIL group (2.5 mg/kg,p.o), irradiation group (rats were exposed to single shot at a dose of 10 Gy to induce liver damage), and SIL + irradiation group. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were evaluated. Liver samples were used to evaluate oxidative stress indicators, reduced glutathione (GSH), malondialdehyde (MDA), nitric oxide(NO), Hepatic antioxidant nuclear factor erythroid 2-related factor 2(Nrf2), and apoptoticp53 upregulated modulator of apoptosis(P53) gene expression were determined by Western blot analysis. Immunohistochemical analysis for hepatic nuclear factor-kappa B (NF-κB) and silent information regulator-1(SIRT1) were performed along with histopathological examination.</div></div><div><h3>Results</h3><div>SIL effectively diminished inflammation by reducing p–NF–κB-p65 and increasing Nrf2 and SIRT 1 expression. Additionally, SIL restrained apoptosis by reducing P53 protein expressions. Moreover, SIL significantly improved radiation-induced histopathological changes.</div></div><div><h3>Significance</h3><div>SIL preventing hepatotoxicity associated with radiation exposure.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"200 ","pages":"Article 115373"},"PeriodicalIF":3.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of toxic metals and trace elements in breast milk of mothers and their health risks to infants: A cross-sectional study in Ardabil, Northwest Iran","authors":"Abdollah Dargahi ,&nbsp;Hamed Zandian ,&nbsp;Fateme Samiee ,&nbsp;Shahla Farzipour ,&nbsp;Negin Sheikhmemari ,&nbsp;Salva Kazemipour-Khabbazi","doi":"10.1016/j.fct.2025.115389","DOIUrl":"10.1016/j.fct.2025.115389","url":null,"abstract":"<div><div>This research aimed to assess the potential health risks for infants and measure the concentrations of heavy metal substances in the breast milk of mothers residing in Ardabil, Iran. The study was descriptive and cross-sectional in nature. Ten health centers in Ardabil City were selected for the research. The ages of participating mothers ranged from 19 to 39 years, and breast milk samples were collected from those who were 1–12 months postpartum. A 25-item questionnaire was used to evaluate the participants' exposure to heavy metals in their environment and diet. Data analysis was performed using the non-parametric Mann-Whitney <em>U</em> test, resulting in a p-value greater than 0.05. The average body mass index (BMI) of breastfeeding mothers was 26.26 ± 3.73. Spike recovery values ranged from 92 % to 106 %, indicating reliable performance within the ICP-MS range. The limit of detection (LOD) during routine sample analysis was 0.001 μg/L. The daily intake (DI) of lead (Pb), arsenic (As), and chromium (Cr) for infants was calculated. According to the findings, copper (Cu) had the highest average concentration in breast milk at 803.94 μg/L, while cadmium (Cd) had the lowest at 1.87 μg/L. Additionally, potassium (K) exhibited the highest average concentration at 490.49 mg/L, whereas molybdenum (Mo) had the lowest at 0.8 μg/L. The average daily intake of Pb, As, and Cr through breastfeeding was measured at 3.39, 0.799, and 3.47 μg/kg-bw/day, respectively. The results confirmed the presence of mercury (Hg), As, and Pb in every milk sample collected from lactating mothers in Ardabil, indicating potential exposure of infants to elevated levels of toxic heavy metals.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"200 ","pages":"Article 115389"},"PeriodicalIF":3.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interaction of environmental fluoride exposure and gut microbes: Potential implication in the development of fluorosis in human subjects.","authors":"Neha Rawat, Saravanadevi Sivanesan, Gajanan Sitaramji Kanade, Amit Bafana","doi":"10.1016/j.fct.2025.115388","DOIUrl":"10.1016/j.fct.2025.115388","url":null,"abstract":"<p><p>Fluoride exposure primarily occurs through contaminated water and leads to fluorosis, which is a global health concern. After ingestion, fluoride is absorbed via gastrointestinal tract, where it interacts with the gut microbiota. While animal studies have explored fluoride's effects on gut microbiota, no human studies have yet been conducted. Most research emphasizes metagenomic diversity, neglecting isolation and characterization of pure cultures for further applications. Additionally, the association between gut microbiota with fluorosis outcomes in fluoride-exposed populations is unexplored. This study characterizes and compares the cultivable gut microbiota in the fluoride-exposed population with (symptomatic, group II) or without (asymptomatic, group I) signs of skeletal fluorosis along with unexposed control (group III). Group I displayed higher abundance of Firmicutes (58.58 %), group II had predominance of Proteobacteria (61.25 %) while group III showed similar abundance of Proteobacteria (50.38 %) and Firmicutes (49.51 %). On analyzing short-chain fatty acid (SCFA) profiles, group I isolates produced higher isobutyric acid (1.31 ± 0.9 mM) than group II (0.71 ± 0.35 mM), while group II produced more isovaleric acid (0.8 ± 0.41 mM) than group I (0.61 ± 0.08 mM) (p < 0.05). These findings suggest that gut microbiota and SCFAs alteration may influence bone metabolism, affecting the fluorosis progression.</p>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"115388"},"PeriodicalIF":3.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigallocatechin-3-gallate as an effective inhibitor of vascular endothelial dysfunction induced by endothelial-localized myeloperoxidase","authors":"Rong Tian,&nbsp;Ya-Di Yang,&nbsp;Naihao Lu","doi":"10.1016/j.fct.2025.115392","DOIUrl":"10.1016/j.fct.2025.115392","url":null,"abstract":"<div><div>In inflammatory vasculature, the leukocyte-released myeloperoxidase (MPO) is internalized by endothelial cells and this enzyme promotes endothelial dysfunction by catalytically producing strong oxidant, hypochlorous acid (HOCl). Herein, we developed epigallocatechin-3-gallate (EGCG, the main polyphenolic flavonoid found in green tea) as a novel endothelial-targeted MPO inhibitor. It was shown that culture of MPO and EGCG with vascular endothelial cells could result in their transport into the sub-endothelial space. EGCG significantly suppressed the consumption of enzyme's substrate H₂O₂ and generation of HOCl catalyzed by endothelial-transcytosed MPO. The binding of EGCG to the hydrophobic domain near the distal active heme cavity of enzyme was proposed by molecular docking and was suggested for the inhibitive effect of flavonoid on MPO activity. In vivo, EGCG attenuated lipopolysaccharide (LPS)-induced endothelial dysfunction in mouse aortas, while it inhibited the infiltration of active MPO into vascular walls. Furthermore, MPO-deficient mice were resistant to the protective effects of EGCG on LPS-induced vascular dysfunction, as compared to wild-type mice. These studies showed that EGCG effectively inhibited local oxidative reactions and endothelial dysfunction catalyzed by vascular-bound MPO. EGCG represents a versatile class of natural antioxidant drugs applicable to target endothelial-transcytosed MPO in inflammatory vasculature.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"200 ","pages":"Article 115392"},"PeriodicalIF":3.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in mycotoxin detection techniques and the crucial role of reference material in ensuring food safety. A review","authors":"Tiisetso Colleen Maphaisa ,&nbsp;Oluwakamisi Festus Akinmoladun ,&nbsp;Oluwasola Abayomi Adelusi ,&nbsp;Mulanda Mwanza ,&nbsp;Fabian Fon ,&nbsp;Emmanuel Tangni ,&nbsp;Patrick Berka Njobeh","doi":"10.1016/j.fct.2025.115387","DOIUrl":"10.1016/j.fct.2025.115387","url":null,"abstract":"<div><div>Mycotoxins, toxic secondary metabolites produced by fungi, pose a significant threat to food safety and human health. The occurrence of mycotoxins in food commodities necessitates accurate and reliable detection methods. Advanced detection techniques, such as chromatographic techniques and immunochemical assays, have improved sensitivity and specificity. However, the lack of standardized reference material, particularly in less privileged countries, hinders method validation and proficiency testing, ultimately affecting mycotoxin testing and regulation. Moreover, these techniques are complex as they require specialized equipment, and well-trained personnel, thus limiting their practical applications. This comprehensive review provides an up-to-date overview of the occurrence of mycotoxins and recent advancements in detection methods. It examines the crucial role of mycotoxin standards as reference materials for ensuring reliable results in mycotoxins analysis in agriculture commodities. The review addresses emerging challenges, knowledge gaps, and future research directions in mycotoxin detection and reference material development. By synthesizing existing literature, this review aims to provide valuable resources for researchers, policymakers, and other stakeholders in food safety, highlighting the importance of integrated approaches to mitigate mycotoxin contamination and ensuring food safety.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"200 ","pages":"Article 115387"},"PeriodicalIF":3.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"20-Week toxicity study of rotigotine behenate extended-release microspheres for intramuscular injection in sprague dawley rats","authors":"Wenjing Lv ,&nbsp;Hong Zhang ,&nbsp;Yumeng Chen ,&nbsp;Mengting Wu ,&nbsp;Caiyi Qin ,&nbsp;Zhicong Yin ,&nbsp;Xinyu Zhao ,&nbsp;Wei Guo ,&nbsp;Xiaobo Cen ,&nbsp;Xin Yu ,&nbsp;Jingwei Tian","doi":"10.1016/j.fct.2025.115384","DOIUrl":"10.1016/j.fct.2025.115384","url":null,"abstract":"<div><div>Based on the concept of continuous dopaminergic stimulation (CDS), Rotigotine Behenate extended-release microspheres for injection (RBEM) are currently under development. To support human clinical trials of RBEM, a 20-week repeat-dose toxicity study was conducted. SD rats intramuscularly received RBEM (60, 180, and 540 mg/kg) once every 4 weeks for 5 repeated doses followed by a 12-week recovery period, no clear sex difference was noted in the plasma exposure of rotigotine in rats, and the exposure generally increased in a dose-proportional manner. No obvious systemic toxicity occurred. Ovarian corpus luteum and breast acinar hypertrophy in rats were believed to be associated with the activation of dopamine receptors by RBEM and decreased prolactin levels. The reversible vacuolar degeneration or foamy macrophage infiltration at the injection site, adjacent tissues, and alveoli of rats were associated with local inflammation and foreign body removal reaction caused by PLGA and SCMC. In this study, the non-observed-adverse-effect-level (NOAEL) in rats was 540 mg/kg (based on rotigotine), which was equivalent to 24 times the maximum clinical recommended dose of RBEM, 448 mg/person/28 days (expressed as the dose of rotigotine behenate). In conclusion, RBEM exhibited a good safety margin and can be used in phase I clinical trials. <strong>Keywords</strong>: Parkinson's disease; RBEM; Continuous dopaminergic stimulation; Repeated dose toxicity.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"200 ","pages":"Article 115384"},"PeriodicalIF":3.9,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effects of anthocyanins on the nervous system injury caused by fluoride-induced endoplasmic reticulum stress in rats","authors":"Dan Wei ,&nbsp;Shiwen Tan ,&nbsp;Shujuan Pang ,&nbsp;Bingshu Liu ,&nbsp;Qiong Zhang ,&nbsp;Siqi Zhu ,&nbsp;Guiyu Fu ,&nbsp;Dianjun Sun ,&nbsp;Wei Wei","doi":"10.1016/j.fct.2025.115386","DOIUrl":"10.1016/j.fct.2025.115386","url":null,"abstract":"<div><div>Long-term fluoride exposure can produce neurotoxicity. Anthocyanins, as antioxidants, have a certain protective effect in nerve damage. This study aimed to investigate the protective role of anthocyanins in fluoride-induced neurological damage due to endoplasmic reticulum stress (ERS). Using a fluoride-exposed Wistar rat model, we assessed learning memory capacity and pathologic and ultrastructural injury. The level of oxidative stress (OS) in vivo was detected by colorimetric method, the level of ERS was analyzed by immunohistochemistry, and the apoptosis of neuronal cells was observed by TUNEL staining. The results showed that fluoride exposure could decrease the learning and memory ability in rats, and led to histopathological and ultrastructural damage in the hippocampal CA1, CA3 and cortical regions. Fluoride exposure-induced OS in vivo, which further activates ERS, which was manifested by increased levels of ERS-related proteins GRP78, Caspase 12, and Caspase 3 in hippocampal CA1, CA3, and cortical regions, and eventually led to a significant increase in neuronal apoptosis rate. Notably, after anthocyanins treatment, pathological and ultrastructural damage was restored, the level of OS and ERS were significantly restored, and the apoptosis rate of neuronal cells was significantly reduced. In summary, as nutritional interventions, anthocyanins exert a protective role in fluoride-induced neurological injury.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"200 ","pages":"Article 115386"},"PeriodicalIF":3.9,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute ivermectin toxicity on skin and brain tissue of adult albino rats: Evaluation of the role of Flumazenil and Vitamin C as new treatment modalities","authors":"Fatma Nada Khalifa ,&nbsp;Sara Adel Hosny ,&nbsp;Lamiaa Mohammed Matter ,&nbsp;Dena Mohamed Naguib Abdel Moawed ,&nbsp;Basant Adel Al Dreny ,&nbsp;Hind A. Elsawi ,&nbsp;Asmaa Mohammad Moawad","doi":"10.1016/j.fct.2025.115383","DOIUrl":"10.1016/j.fct.2025.115383","url":null,"abstract":"<div><div>Ivermectin, a natural antiviral drug, has been recommended for treating various diseases, including Coronavirus Disease 2019. This study aimed to evaluate the potential histopathological and biochemical changes in the skin and brain of adult albino rats treated with ivermectin, as well as the effectiveness of Vitamin C and flumazenil in their treatment. Thirty rats were divided into five treatment groups, each containing six rats. After a week of acclimatization, different doses of ivermectin, Vitamin C, and flumazenil were administered to the rats. The rats were then euthanized. Histological and micro ribonucleic acid (miRNA) analysis of the skin and brain tissues, immunohistochemistry, and plasma collection from tail vein puncture were conducted to measure dopamine and interleukin 5 levels. The control group showed minimal acute toxicity, with an increase in hsa-miR535a-5p, dopamine, interleukin 5 (IL-5), and p-glycoprotein levels. In conclusion, the acute toxic effects of ivermectin in rats led to significant histological and morphological changes in both brain and skin tissues, along with oxidative stress and disruptions in P-glycoprotein, inflammatory cytokines, and the inflammatory response. Flumazenil and vitamin C may help normalize neuronal signaling, alleviate oxidative stress, and enhance dopamine release.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"200 ","pages":"Article 115383"},"PeriodicalIF":3.9,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}