Toxicology Research最新文献

{"title":"Immune modulatory potential of <i>Carica papaya</i> against asbestos-induced acute lung injury through down-regulation of NF-kB and MAPK pathways.","authors":"Usman Haider, Bilal Aslam, Shamshad Ul Hassan, Zia Ud Din Sindhu","doi":"10.1093/toxres/tfaf140","DOIUrl":"https://doi.org/10.1093/toxres/tfaf140","url":null,"abstract":"<p><p>Inflammation is the primary response to any sort of injury that provokes an immune system and release of inflammatory mediators. The aim of current study is to explore the anti-inflammatory and therapeutic potential of <i>Carica papaya</i> against inflammation caused by environmental particles i.e. silica, dust, and asbestos in rats. The study included four groups (G1 NC, G2 PC, G3 M.T and G4 H.T) with each having eight male albino rats raised for the period of 14 days. Rats were decapitated on day 14^th and sampling was done for CBC, serum analysis, qTR PCR, and histopathology. Data analysis was done through ANOVA and Tukey's Test. There was significant <i>(P ≤ 0.05)</i> decrease of diffrential leucoctyic cells count in H.T group as compared to PC group. Serum lipid profile showed siginificant <i>(P ≤ 0.05)</i> reduction of choltesrol, triglyceride, and LDL, while enhanced HDL concentration in H.T and M.T groups as comparision to PC group. Heat map was generated for gene expression through qRT PCR which revealed the significant <i>(P ≤ 0.05)</i> up-regulation of IL-1 beta, IL-6, IL-33, IL-17, INF-gamma, TNF alpha, TLR-4, Traf-4 and Traf-6. Whereas IL-4, IL-10, and IGF-1 were being significantly <i>(P ≤ 0.05)</i> down- regulated in PC and increased in M.T and H.T groups. Microscopic examination exhibits distorted parenchyma and destructed walls of alveoli in PC while restoration of parenchyma and alveolar structure was seen in treatment groups. It was concluded that <i>C. papaya</i> has potent anti-inflammatory and mitigate the oxidative stress due to inflammation.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 5","pages":"tfaf140"},"PeriodicalIF":2.1,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative In vitro and In Silico analysis of marine Actinobacterium, <i>Streptomyces rubrogriseus</i>-derived metabolites as quorum sensing inhibitors against <i>Chromobacterium violaceum</i>.","authors":"Ambily Balakrishnan, Kottayath G Nevin, Arunkumar Gangadharan, V P Limnamol","doi":"10.1093/toxres/tfaf142","DOIUrl":"https://doi.org/10.1093/toxres/tfaf142","url":null,"abstract":"<p><p>Quorum-sensing (QS), a bacterial communication mechanism regulating virulence, biofilm formation, and environmental adaptation, represents a promising target for antivirulence therapies. Unlike conventional antibiotics, QS inhibition disrupts bacterial coordination without promoting antimicrobial resistance. Marine actinobacteria, well adapted to extreme habitats, are a rich source of bioactive quorum-sensing inhibitors (QSI). This study evaluates the QSI activity of ethyl acetate (EA) extract from a marine actinobacterium, <i>Streptomyces rubrogriseus</i>, against <i>Chromobacterium violaceum</i> 12472, a QS model organism. Marine actinobacteria were isolated from Kochi coastal sediments, and the most potent strain was identified via 16S rDNA sequencing. Crude extract was prepared through solid-state fermentation and solvent extraction. Antivirulence assays included MIC determination, violacein inhibition, biofilm suppression, AHL quantification, and swarming motility tests. Gene expression changes were analyzed by RT-qPCR, while bioactive metabolites were fractionated using silica gel chromatography and characterized by HR-LC-MS. In silico approaches, including molecular docking and molecular dynamics (MD) simulations, were applied to predict compound-receptor interactions. The extract showed a MIC of 128 μg/mL. At 64 μg/mL (sub-MIC), it inhibited biofilm formation (92%), violacein production (78%), and AHL levels (74%), while impairing motility. RT-qPCR confirmed downregulation of the QS-regulated <i>cviR</i> gene. HR-LC-MS profiling identified several metabolites, among which 3-dehydrosphinganine exhibited the highest docking affinity for the CviR receptor (Glide score - 9.688 kcal/mol). MD simulations further validated binding stability of 3-dehydrosphinganine and hexadecasphinganine. These findings highlight marine actinobacteria-derived metabolites as potent QS inhibitors with significant antivirulence potential.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 5","pages":"tfaf142"},"PeriodicalIF":2.1,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heavy metal concentration and DNA damage in tilapia (<i>Oreochromis niloticus</i> linnaeus, 1758) and catfish (<i>Clarias gariepinus</i> Burchell, 1822) from contaminated Ala River, Akure, Nigeria.","authors":"Okunola Adenrele Alabi, Foyinsola Mabel Fatile, Michael Olufemi Ashamo","doi":"10.1093/toxres/tfaf141","DOIUrl":"https://doi.org/10.1093/toxres/tfaf141","url":null,"abstract":"<p><p>This study investigated heavy metal contamination in <i>Clarias gariepinus</i>, <i>Oreochromis niloticus,</i> and water from the polluted Ala River using atomic absorption spectroscopy. Carcinogenic and non-carcinogenic risks were assessed per USEPA guidelines. DNA damage in fish was evaluated via micronucleus assay and nuclear aberration analysis, with Alanine aminotransferase (ALT), Aspartate Aminotransferase (AST), and Alkaline Phosphatase (ALP) activities examined for potential mechanisms. Cadmium (Cd), Chromium (Cr), Nickel (Ni), and Lead (Pb) levels in fish and water exceeded WHO/FAO limits, with higher concentrations in <i>C. gariepinus</i>. Health risk assessments showed that estimated daily intake (EDI) of these metals in children and adults exceeded safe limits, particularly from <i>C. gariepinus</i> consumption. Consumption of Ala river water posed health risks, as Cd and Pb EDI values exceeded safe limits for adults and children. High hazard index levels in <i>C. gariepinus</i>, <i>O. niloticus</i>, and water indicated non-carcinogenic risks, while total cancer risk values surpassed the threshold (>10^-4), signifying significant cancer risks. DNA damage analysis showed a statistically significant (p ≤ 0.05) increase in micronuclei (MN) and other nuclear aberrations, with higher MN frequency in <i>C. gariepinus</i>. ALT, AST, and ALP levels were elevated, indicating physiological stress. The study underscores severe metal contamination in Ala River, urging stricter pollution control measures.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 5","pages":"tfaf141"},"PeriodicalIF":2.1,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational and experimental assessment of the toxicological effects of copper oxide nanoparticles on haematological and biochemical parameters in albino mice.","authors":"Muhammad Yasir Abbas, Ali Umar, Muhammad Waseem Aslam, Waseem Ul Ghafoor, Noman Nazeer, Misbah Ullah Khan, Komal Farghama, Muhammad Saleem Khan, Muhammad Wajid, Rashid Iqbal, Hayat Ullah, Gaber E Eldesoky, Mohammad Shahidul Islam, Hamid Ali","doi":"10.1093/toxres/tfaf139","DOIUrl":"https://doi.org/10.1093/toxres/tfaf139","url":null,"abstract":"<p><p>The investigation delves into biological interactions of CuO-NPs throughout study focusing on their synthetic structure together with their functional characteristics and their dangerous nature. The production of CuO-NPs happened when copper (II) sulfate pentahydrate underwent a chemical reduction process with D-glucose under NaOH conditions to stabilize pH levels. Structural and chemical evaluations used SEM, XRD and FTIR as their analytical techniques. Male albino mice received 15 mg/kg (low dose, NPS-L) and 30 mg/kg (high dose, NPS-H) for 28 days, through which researchers evaluated toxicological effects. The investigators measured blood cell counts together with serum lipids, liver and kidney enzyme assays. Significant dose-oriented toxic behavior of CuO-NPs led to substantial variations in WBCs, RBCs, and hemoglobin, along with organ function test results. The microscopic evaluation of high-dose groups showed necrosis together with glomerular destruction and inflammatory findings. Male albino mouse exposure to low and high doses for 28 days decreased both catalase and superoxide dismutase activity levels. Pharmacokinetic studies demonstrated that CuO-NPs exhibited moderate solubility together with small blood-brain barrier permeability and minimal metabolic enzyme disruption, thus indicating limited circulation and avoidance of neurotoxicity. Toxicity screenings demonstrated that substance produced negligible harm to liver tissues and hearts and had low toxicity for aquatic life while showing minimal impact on endocrine system. While CuO-NPs present opportunities in biomedical sector research, they prove toxic at different dosage levels and require additional research for safe medical deployment. Research shows that CuO-NPs require thorough preclinical evaluation regarding their biological accessibility and safety standards before biomedical and environmental applications can be employed.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 5","pages":"tfaf139"},"PeriodicalIF":2.1,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Examination of the effects of polyunsaturated fatty acids on the alzheimer model caused by amiloid β_1-42 toxicity in human SHSY5Y cells by in vitro methods.","authors":"Mualla Pınar Elci, Sema Ören, Ece Miser-Salihoglu, Sevgi Yardim-Akaydin","doi":"10.1093/toxres/tfaf130","DOIUrl":"10.1093/toxres/tfaf130","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a progressive, chronic disease characterized by impaired cognitive function. Currently, there is no complete cure for ad; current treatments are aimed at reducing symptoms and slowing the progression of the disease. It is thought that the amount of fatty acid consumption and the balance between them may be protective against neurological diseases. In this study, it was aimed to determine the protective effects of Ω3/Ω6 polyunsaturated fatty acids ratios in Aβ_1-42-induced ad model in human neuroblastoma (SH-SY5Y) cells. The viability of cells was determined by MTT assay. The percentage of apoptotic cells was determined by FITC-conjugated Annexin-V/PI. ROS, MMP and cell cycle analysis were performed by flow cytometry. The amount of acetylcholinesterase enzyme was measured with a commercial kit. 48 h after the application, a statistically significant decrease was observed in the MTT test in the 1/1, 1/2 and 1/8 groups and in the amount of AChE in the 1/4, 1/8 and 1/16 groups. According to apoptosis findings, all ratios were observed to reduce cell viability compared to the control group. ROS and MMP levels were detected to decrease in all groups compared to the control group. The highest neuroprotective effect against oxidative stress was observed at 1/1 dose. Aβ_1-42 induced blockade of the cell cycle was observed to be partially corrected by 1/8 dose. As a result, it can be said that Ω6 and Ω3 fatty acids, when used in 1/4 and 1/8 doses can provide a protective effect against Alzheimer's disease.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf130"},"PeriodicalIF":2.1,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12392398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144936262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MiR-1291 mediates the protective effect of sevoflurane preconditioning against hypoxia/reoxygenation-induced myocardial cell injury.","authors":"Jingyi Shi, Shaoke Hou, Xinyu Yao","doi":"10.1093/toxres/tfaf122","DOIUrl":"10.1093/toxres/tfaf122","url":null,"abstract":"<p><p>The protective effects of sevoflurane (Sev) in cardiovascular disease have been well documented in studies. The investigation aimed to clarify the contribution of miR-1291 to the pathophysiological process of hypoxia-reoxygenation (H/R)-induced cardiomyocyte injury in the setting of Sev preconditioning. H/R cell models were constructed with AC16 cells and the cell models were pretreated with 1%, 1.5% and 2% concentrations of Sev. Quantitative reverse transcription polymerase chain reaction was performed to detect miR-1291 and NF2 expression in cells. Cell viability was assessed using the cell counting kit-8 assay. Apoptosis was evaluated via flow cytometry. Cellular cardiac troponin I (cTnI), lactate dehydrogenase (LDH), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels were detected by enzyme-linked immunosorbent assay. Dual luciferase reporter gene assay and RIP analysis were applied to validate the binding of miR-1291 to NF2. In the H/R cell model, miR-1291 was downregulated, and this was accompanied by reduced cell viability, increased apoptosis, and elevated levels of cTnI, LDH, IL-6 and TNF-α. In contrast, inhibition of miR-1291 expression impaired the protective effect of Sev on cardiomyocytes. NF2 was a downstream target gene of miR-1291, and miR-1291 negatively regulated the expression of NF2. Knockdown of NF2 expression alleviated the effects of miR-1291 inhibition on Sev-treated cells. Sev attenuates H/R-induced cardiomyocyte injury by regulating miR-1291/NF2 expression and inhibiting apoptosis and inflammatory responses. This study unveils a novel mechanism of Sev-mediated myocardial protection, offering theoretical support and potential therapeutic targets for myocardial injury prevention and treatment.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf122"},"PeriodicalIF":2.1,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12392403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144936272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Counteracting effects of Ethanolic extract of <i>allium Sativum</i> on Perfluorooctanoic acid-induced cardiotoxicity: insights into Keap1-Nrf2/PPARα pathways.","authors":"Eman El-Sayed Khayal, Hend S Eisa, Marwa Ahmed Abass, Shaimaa A Abdelrhman, Samar Sakr","doi":"10.1093/toxres/tfaf129","DOIUrl":"10.1093/toxres/tfaf129","url":null,"abstract":"<p><p>Perfluorooctanoic acid (PFOA) is a synthetic chemical belonging to per and poly-fluoroalkyl substances. It persists in the environment and accumulates in human bodies, leading to significant health concerns. <i>Allium sativum</i> (garlic) is acknowledged for its nutritional and anti-oxidative properties. Current research investigated the efficacy of <i>A. sativum</i> ethanolic extract against PFOA-induced cardiotoxicity. Fifty adult albino rats were grouped equally into five groups: control, vehicle, <i>A. sativum</i> (300 mg/kg), PFOA (25 mg/kg), and PFOA and <i>A. sativum</i>. Rats were daily gavaged with treatments for 8 weeks. Serum samples were used for measuring lactate dehydrogenase (LDH), total cholesterol, and triglycerides (TG) levels. Cardiac tissues were used for assessing oxidative stress biomarkers (heme oxygenase1 (HO1), catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA)), and nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB). Also, the gene expression for nuclear factor erythroid-derived 2-like 2 (Nrf2), Kelch-like ECH-associated protein1 (Keap1), and peroxisome proliferator-activated receptor α (PPAR α) was determined. Cardiac tissues had undergone histopathological and immunohistochemical examination for caspase-3. Results revealed that PFOA exposure decreased the anti-oxidant enzymes (HO1, CAT, SOD), and markedly elevated levels of both MDA and NF-κB. PFOA inhibited the Nrf2 pathway as presented by the downregulated Nrf2 and upregulated Keap1 genes. Additionally, PFOA disturbed lipid metabolism via PPAR α downregulation. These changes were supported by histopathological changes and increased caspase-3 immunoexpression. A combination of <i>A. sativum</i> extract with PFOA provided significant protection against the aforementioned changes. Results suggested that <i>A. sativum</i> is an effective natural product that can attenuate PFOA-induced cardiotoxicity.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf129"},"PeriodicalIF":2.1,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12381759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144936812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LPS mediated neuronal c-Fos activation: whole-brain mapping, site and time effect in intoxicated mice.","authors":"Mona N Hussein, Khalid S Alotaibi, Saed A Althobaiti, Shatha B Albattal, Xiao Ke, Jinxia Dai, Gang Cao, Mohamed Mohamed Soliman","doi":"10.1093/toxres/tfaf131","DOIUrl":"10.1093/toxres/tfaf131","url":null,"abstract":"<p><p>Lipopolysaccharide (LPS; a bacterial endotoxin) treatment causes acute inflammatory conditions. Acute inflammation causes the brain to activate neurons in some brain nuclei known as circumventricular organs. The c-Fos immunoreaction could be used to assess this neural activity. The current study aimed to check the activated neurons in time and site effect during toxicity and inflammation induced by LPS. The c-Fos antibody immunofluorescence labeling was checked at one, three, and six hours after LPS intoxication. Moreover, a retrograde viral tracing approach was employed to verify the neuronal connections among certain brain nuclei that were activated. The results indicated the activation of several brain nuclei in the hippocampus, epithalamus, thalamus, hypothalamus, basal ganglia, midbrain, and medulla oblongata. The type of brain nuclei and the number of neurons that were activated in relation to the duration of acute inflammation were clearly different. Furthermore, this research demonstrated that these active brain nuclei were connected neuronally. Ultimately, acute inflammatory responses induced by LPS treatment activated dorsal raphe serotonergic neurons. Twenty-two brain nuclei were shown to be involved in the neuroinflammatory response via whole-brain mapping. One hour after LPS administration, neurons in the dorsomedial hypothalamic nucleus (DM), lateral septal nucleus (LS), and solitary tract nucleus (SOL) were significantly activated. However, the sensory circumventricular organs (CVOs) were activated three hours after LPS treatment. It was also demonstrated that dorsal raphe serotonergic neurons play a vital role in the body's reaction to acute inflammation. This study confirmed the involvement of dorsal raphe serotonergic neurons in response to acute inflammation and toxicity induced by LPS.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf131"},"PeriodicalIF":2.1,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12381757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144936188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Flumetralin based plant growth regulator used in tobacco cultivation induces immune and cytotoxicity in vitro.","authors":"Aline Mocellin Conte, Fernanda Mocellin Conte, Larissa V Cestonaro, Maria Fernanda Nunes Ribeiro, Rodrigo F da Silva, Renata De Faveri, Larissa Benvenutti, Solange C Garcia, José Roberto Santin, Rodrigo Ligabue-Braun, Bruno Dutra Arbo, Marcelo Dutra Arbo","doi":"10.1093/toxres/tfaf118","DOIUrl":"10.1093/toxres/tfaf118","url":null,"abstract":"<p><p>Tobacco production lasts about 10 months and various pesticides are used, including growth inhibitors, which flumetralin is the most used. This is an herbicide that acts as a synthetic and plant growth regulator. Therefore, this work aimed to evaluate the toxicity of the growth regulator flumetralin in RAW 264.7 and 3T3 cell lines. Cytotoxicity was assessed by MTT reduction and neutral red uptake assays after 24 h of incubation with flumetralin. Mitochondrial integrity, production of reactive species and cytokine profile were evaluated in both cell lines. Furthermore, NO production was evaluated in RAW 264.7 cells, while comet assay was evaluated in 3T3 cells. An increase in reactive species production was observed in both cell lines. In RAW 264.7 cells were observed an increase in mitochondrial membrane potential, while 3T3 cells presented a mitochondrial depolarization. At all tested concentrations, flumetralin increased TNF-α levels and decreased IL-10 levels in RAW 264.7, and increased TNF and IL-1ß in 3T3 cells. In addition, at all tested concentrations, flumetralin induced DNA damage in 3T3 cells. It was possible to observe the cytotoxic effect of flumetralin on the tested cell lines, as well as a possible generation of an inflammatory response and immune deregulation.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf118"},"PeriodicalIF":2.1,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12371405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144936183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, in-vitro, <i>in-silico</i>, and global DNA methylation studies of curcumin-benzoquinone analog in triple-negative breast cancer (TNBC) cells.","authors":"Başak Günçer, Funda Özkök, Ebru Hacıosmanoğlu Aldoğan, Yasemin Oyacı, Esra Nazlıgül, Bilge Özerman Edis, Sama Akbarzadeh, Nihal Onul, Atilla Akdemir, Vildan Enisoğlu Atalay, Sacide Pehlivan","doi":"10.1093/toxres/tfaf128","DOIUrl":"10.1093/toxres/tfaf128","url":null,"abstract":"<p><p>Curcumin is a well-known anticancer agent used for many malignancies; however, its low bioavailability and solubility limit its use in clinical applications. To enhance its efficacy, we synthesized a novel curcumin-benzoquinone analog, JWB1 (3), and evaluated its anticancer potential against triple-negative breast cancer (TNBC) in vitro. We designed JWB1 (3) and structurally identified it using NMR, FTIR, MS, and UV-Vis techniques. The MTT assay was used to evaluate JWB1 (3) cytotoxicity in the MDA-MB-231, MCF-7, and HUVEC cell lines. Flow cytometry was used to examine apoptotic activation and reactive oxygen species (ROS) levels. Global DNA methylation was measured using an ELISA kit. Docking studies and molecular dynamics simulations revealed potential JWB1 (3) interactions with double-stranded DNA (dsDNA). JWB1 (3) showed selective cytotoxicity towards MDA-MB-231 cells (IC₅₀: 2.94 μg/mL, SI: 23.5 in 24 h), with minimal effects on HUVECs. Treatment with 10 μg/mL JWB1 (3) increased global DNA methylation levels in MDA-MB-231 cells (from 0.87% to 1.92%) more than in MCF-7 cells. The apoptosis assay showed that JWB1 (3) significantly induced MDA-MB-231 cells in the early apoptosis phase (early apoptosis: 45.65% vs. 2.95% in the controls). Furthermore, post-treatment, cancer cells showed a notable decrease in ROS levels. Supported by 100 ns molecular dynamics simulation, molecular docking investigations also showed a stable 3D structure and intercalation of JWB1 (3) with DNA. These findings imply that JWB1 (3) has notable anticancer potential against TNBC by inducing apoptosis, epigenetic modification, and DNA interaction.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf128"},"PeriodicalIF":2.1,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12365976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144936249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}