{"title":"Gene expression profiles related to apoptosis and levels of DNA oxidative damage in primary dermal fibroblast cells (ATCC® PCS-201-012TM) treated with zirconium oxide nanoparticles","authors":"Gizem Barut , Ayla Çelik","doi":"10.1016/j.fct.2025.115446","DOIUrl":"10.1016/j.fct.2025.115446","url":null,"abstract":"<div><div>Nanoparticles have attracted growing interest in recent years. They are small and can easily penetrate into cells. We investigated the genotoxic, cytotoxic, and apoptotic effects of zirconium nanoparticles on dermal fibroblast cells, the comet assay, Xcelligence system, and apoptotic gene expression, respectively. The comet assay analysis showed a non-signifcant increase in the genetic damage index and the percentage of damaged cells in the groups exposed to 10 and 20-nm zirconium oxide nanoparticles. Xcelligence system analysis observed a decrease in the indices of cells exposed to 10 and 20 nm zirconium oxide nanoparticles in the 48th-hour, 72nd-hour, and 96th-hour data. It was observed that caspase 3 and caspase 8 gene expression levels were suppressed in cells exposed to 10 and 20 nm zirconium oxide nanoparticles. Compared to the negative control group, this suppression was significant in the 10 nm groups (p < 0.01) while it was not significant in the 20 nm groups. Although zirconium oxide nanoparticles do not show toxicity and genotoxicity at a given concentration, but the overall mechanism is still not clear regarding the consequences of these nanoparticles use and its efect on living system. However, our apoptotic gene expression studies concluded that the nanoparticle size, particularly 10 nm, had an impact on gene expression.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"201 ","pages":"Article 115446"},"PeriodicalIF":3.9,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143873959","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}
A.M. Api , A. Bartlett , D. Belsito , D. Botelho , M. Bruze , A. Bryant-Friedrich , G.A. Burton , M.A. Cancellieri , H. Chon , M. Cronin , S. Crotty , M.L. Dagli , W. Dekant , C. Deodhar , K. Farrell , A.D. Fryer , L. Jones , K. Joshi , A. Lapczynski , D.L. Laskin , Y. Thakkar
{"title":"Update to RIFM fragrance ingredient safety assessment, amyl hexanoate, CAS registry number 540-07-8","authors":"A.M. Api , A. Bartlett , D. Belsito , D. Botelho , M. Bruze , A. Bryant-Friedrich , G.A. Burton , M.A. Cancellieri , H. Chon , M. Cronin , S. Crotty , M.L. Dagli , W. Dekant , C. Deodhar , K. Farrell , A.D. Fryer , L. Jones , K. Joshi , A. Lapczynski , D.L. Laskin , Y. Thakkar","doi":"10.1016/j.fct.2025.115463","DOIUrl":"10.1016/j.fct.2025.115463","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"201 ","pages":"Article 115463"},"PeriodicalIF":3.9,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143867744","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}
Laura Lis Ricardi , Felipe Zecchinati , Virginia Gabriela Perdomo , Cecilia Lorena Basiglio , Fabiana García , Maite Rocío Arana , Silvina Stella Maris Villanueva
{"title":"Oxidative stress promotes post-translational down-regulation of MRP2 in Caco-2 cells: Involvement of proteasomal degradation and toxicological implications","authors":"Laura Lis Ricardi , Felipe Zecchinati , Virginia Gabriela Perdomo , Cecilia Lorena Basiglio , Fabiana García , Maite Rocío Arana , Silvina Stella Maris Villanueva","doi":"10.1016/j.fct.2025.115459","DOIUrl":"10.1016/j.fct.2025.115459","url":null,"abstract":"<div><div>The intestinal tract is highly susceptible to oxidative stress (OS), which impairs gut barrier function. Multidrug Resistance-Associated Protein 2 (MRP2) is a key efflux pump in the intestinal transcellular barrier, regulating toxicant and drug disposition. We here evaluated the effects of OS on MRP2 in Caco-2 cells treated with <em>tert</em>-butyl hydroperoxide (TBH). After 24 h, TBH 250 μM increased ROS production and lipid peroxidation while decreasing GSH content and SOD activity, confirming OS induction. Under these conditions, total MRP2 protein levels decreased, while P-gp levels remained unchanged. Correspondingly, MRP2 efflux activity decreased, impairing barrier function against ochratoxin A (OTA), a substrate of MRP2, and exacerbating OTA toxicity. Localization analysis revealed reduced apical MRP2 signal in TBH 250 group, with unchanged mRNA levels, indicating post-transcriptional regulation. Mechanistically, TBH induced rapid MRP2 internalization (30 min), mediated by cPKC and clathrin, without microtubule involvement, followed by proteasomal degradation at 24 h. Both processes were dependent on GSH depletion, as treatment with N-Acetyl-<span>l</span>-Cysteine (NAC) restored GSH levels, MRP2 localization, and activity. We provide here the first evidence that human intestinal MRP2 is post-translationally downregulated under specific OS conditions, highlighting its potential role in exacerbating xenobiotic absorption and toxicity in OS-related human diseases.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"201 ","pages":"Article 115459"},"PeriodicalIF":3.9,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143869413","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}
A.M. Api , A. Bartlett , D. Belsito , D. Botelho , M. Bruze , A. Bryant-Friedrich , G.A. Burton Jr. , M.A. Cancellieri , H. Chon , M. Cronin , S. Crotty , M.L. Dagli , W. Dekant , C. Deodhar , K. Farrell , A.D. Fryer , L. Jones , K. Joshi , A. Lapczynski , D.L. Laskin , Y. Thakkar
{"title":"Update to RIFM fragrance ingredient safety assessment, 4,4a,6,7,8,8a-hexahydro-1,4-methanonaphthalen-5(1H)-one, CAS Registry Number 51519-65-4","authors":"A.M. Api , A. Bartlett , D. Belsito , D. Botelho , M. Bruze , A. Bryant-Friedrich , G.A. Burton Jr. , M.A. Cancellieri , H. Chon , M. Cronin , S. Crotty , M.L. Dagli , W. Dekant , C. Deodhar , K. Farrell , A.D. Fryer , L. Jones , K. Joshi , A. Lapczynski , D.L. Laskin , Y. Thakkar","doi":"10.1016/j.fct.2025.115464","DOIUrl":"10.1016/j.fct.2025.115464","url":null,"abstract":"<div><div>4,4a,6,7,8,8a-Hexahydro-1,4-methanonaphthalen-5(1H)-one was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, photoirritation/photoallergenicity, skin sensitization, and environmental safety. Data show that 4,4a,6,7,8,8a-hexahydro-1,4-methanonaphthalen-5(1H)-one is not genotoxic. The repeated dose, reproductive, and local respiratory toxicity endpoints were evaluated using the Threshold of Toxicological Concern (TTC) for a Cramer Class III material, and the exposure to 4,4a,6,7,8,8a-hexahydro-1,4-methanonaphthalen-5(1H)-one is below the TTC (0.0015 mg/kg/day, 0.0015 mg/kg/day, and 0.47 mg/day, respectively). Data from read-across analog octahydro-7-methyl-1,4-methanonaphtalen-6(2H)-one (CAS # 41724-19-0) provide 4,4a,6,7,8,8a-hexahydro-1,4-methanonaphthalen-5(1H)-one a No Expected Sensitization Induction Level (NESIL) of 5300 μg/cm<sup>2</sup> for the skin sensitization endpoint. The photoirritation/photoallergenicity endpoints were evaluated based on data and ultraviolet/visible (UV/Vis) spectra; 4,4a,6,7,8,8a-hexahydro-1,4-methanonaphthalen-5(1H)-one is not photoirritating/photoallergenic. The environmental endpoints were evaluated; 4,4a,6,7,8,8a-hexahydro-1,4-methanonaphthalen-5(1H)-one was found not to be Persistent, Bioaccumulative, and Toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use (VoU) in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"201 ","pages":"Article 115464"},"PeriodicalIF":3.9,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143843300","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}
Jiaqi Shi , Ying Ma , Nairui Yu , Yi Zhang , Zongfu Cao , Li Guan , Xiaodong Liu , Zhangjian Chen , Guang Jia
{"title":"Key toxic pathways of hepatotoxicity induced by titanium dioxide nanoparticles through multi-omics analysis","authors":"Jiaqi Shi , Ying Ma , Nairui Yu , Yi Zhang , Zongfu Cao , Li Guan , Xiaodong Liu , Zhangjian Chen , Guang Jia","doi":"10.1016/j.fct.2025.115457","DOIUrl":"10.1016/j.fct.2025.115457","url":null,"abstract":"<div><div>The liver is considered a target organ for the accumulation and toxic effects of nanomaterials exposed to the body, especially after oral exposure, but the key toxic pathways have not been fully defined. This study focused on the hepatotoxicity of titanium dioxide nanoparticles (TiO<sub>2</sub> NPs) <em>in vivo</em> and <em>in vitro</em>, and tried to identify key toxic pathways using the concept of systems biology and multi-omics methods. <em>In vivo</em>, protein and metabolomic sequencing were performed on the liver of SD rats (0, 50 mg/kg, 90 days), and 386 differential proteins and 29 differential metabolites were screened out, respectively, and the joint analysis found that they were significantly enriched in alanine, aspartate and glutamate metabolism, and butanoate metabolism. <em>In vitro</em>, exposure to TiO<sub>2</sub> NPs could induce cytotoxicity and omics changes at different molecular levels in human hepatocellular carcinoma cells. Single omic analysis showed that differentially expressed proteins and metabolites were 80 and 222, respectively. The enriched pathways related to steroid biosynthesis, cholesterol metabolism at the combine levels of proteome and metabolome. KEGG enrichment analysis showed that PI3K-Akt signaling pathway and PPAR signaling pathway were both significantly affected <em>in vitro</em> and <em>in vivo</em>. Through multi-omics analysis, this work offered fresh perspectives and avenues for research on the toxicity mechanism of TiO<sub>2</sub> NPs.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"201 ","pages":"Article 115457"},"PeriodicalIF":3.9,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143865090","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}
Kai Liu , Meng Shi , Xin Li , Xiaoli Zeng , Xiaoju Liu
{"title":"Curcumin modulates the PTEN/PI3K/AKT pathway to alleviate inflammation and oxidative stress in PM2.5-Induced chronic obstructive pulmonary disease","authors":"Kai Liu , Meng Shi , Xin Li , Xiaoli Zeng , Xiaoju Liu","doi":"10.1016/j.fct.2025.115460","DOIUrl":"10.1016/j.fct.2025.115460","url":null,"abstract":"<div><div>Ambient fine particulate matter (PM2.5) contributes to the onset and escalation of chronic obstructive pulmonary disease (COPD) through the induction of inflammatory reactions and oxidative stress. Curcumin is a natural polyphenolic compound renowned for the potent antioxidant and anti-inflammatory properties. This research utilized a PM2.5-induced COPD mouse model and BEAS-2B cell line to explore the protective mechanisms of curcumin. The results showed that PM2.5 impaired pulmonary function, exacerbated airway inflammation, and caused structural damage to lung tissue. Elevated levels of inflammatory cytokines such as IL-6, IL-1β, and TNF-α, increased malondialdehyde, and reduced activities of antioxidant enzymes catalase and superoxide dismutase were observed in both mice and BEAS-2B cell line. PM2.5 exposure also suppressed PTEN expression and activated PI3K/AKT signal, and the downstream molecule NF-κB was activated and FoxO1 activity was inhibited. PTEN overexpression partially reversed PM2.5-induced inflammation and oxidative stress <em>in vitro</em>. Curcumin enhanced PTEN expression, inhibited PI3K/AKT and NF-κB activation, and restored FoxO1 activity, alleviating airway inflammation and oxidative stress, while PTEN inhibition attenuated the ameliorating effects of curcumin <em>in vitro</em> and <em>in vivo</em>. In summary, PM2.5 exposure induces COPD inflammation and oxidative stress by disrupting PTEN/PI3K/AKT signaling and curcumin significantly alleviates these effects partially through PTEN/PI3K/AKT signal.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"201 ","pages":"Article 115460"},"PeriodicalIF":3.9,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143874075","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}
Anthia C. Govender, Anil A. Chuturgoon, Terisha Ghazi
{"title":"A review on fumonisin B1-induced mitochondrial dysfunction and its impact on mitophagy and DNA methylation","authors":"Anthia C. Govender, Anil A. Chuturgoon, Terisha Ghazi","doi":"10.1016/j.fct.2025.115458","DOIUrl":"10.1016/j.fct.2025.115458","url":null,"abstract":"<div><div>Fumonisin B<sub>1</sub> (FB<sub>1</sub>) is a food-borne mycotoxin synthesized by <em>Fusarium verticillioides</em> and has been identified as a group 2B carcinogen. Recent research shows that the mitochondria and DNA in cells are targets of FB<sub>1</sub>. Mitophagy is a form of autophagy that functions to break down impaired mitochondria to preserve the overall functionality of the cell. DNA methylation is an epigenetic process that involves the enzymatic transfer of methyl groups from S-adenosylmethionine (SAM) to the C-5 region of the DNA cytosine ring by DNA methyltransferases (DNMTs). DNA methylation plays a key role in maintaining DNA integrity and FB<sub>1</sub> disrupts DNA methylation via FB<sub>1</sub>-induced folate deficiency. However, there is limited research available on the impact of FB<sub>1</sub> on mitophagy as well as FB<sub>1</sub>-induced oxidative stress and its influence on DNA methylation regulation. In this review, we aim to combine and summarize the current information on FB<sub>1</sub>-induced mitochondrial dysfunction, its impact on mitophagy as well as its DNA methylation effects.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"201 ","pages":"Article 115458"},"PeriodicalIF":3.9,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143865089","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}
Shiwen Li , Jingguang Li , Yongning Wu , Xin Liu , Lei Zhang
{"title":"Bayesian benchmark dose assessment of per- and polyfluorinated substances exposure-associated thyroid function disruption during pregnancy","authors":"Shiwen Li , Jingguang Li , Yongning Wu , Xin Liu , Lei Zhang","doi":"10.1016/j.fct.2025.115456","DOIUrl":"10.1016/j.fct.2025.115456","url":null,"abstract":"<div><div>Epidemiological evidence on maternal thyroid function disruption by prenatal exposure to perfluorinated and polyfluorinated substances (PFASs) is limited and inconsistent. The study examined the effects of PFASs exposure during early pregnancy on maternal thyroid function [free thyroxine (FT4), thyroid stimulating hormone (TSH), thyroid peroxidase antibodies (TPOAb) and FT4/TSH ratio]. The associations were evaluated using both single and mixed pollutant models, statistical analyses were further utilized in benchmark dose (BMD) estimations to offer critical references for human health risk assessment. Linear regression was used and then Bonferroni correction adjustment was set up to correct for multiple comparisons. The results revealed a significant association between PFHxS exposure and TSH (β = 0.473; 95 % CI: 0.180, 0.767). According to BKMR mixed-effects models, PFHxS was significantly positively correlated with TSH at the 25th percentile. PFASs were associated with the FT4/TSH ratio at the 25th to 40th percentile. The BMD value of the increasing FT4 effect induced by PFBA and PFPeA in pregnant women were 6.68 ng/mL and 1.37 ng/mL, respectively. The BMDs were obtained for TSH in the case of PFBA (0.33 ng/mL), PFHxS (0.28 ng/mL). Although BMDL<sub>10</sub> is higher than observed for maternal TSH elevation in animal studies, both studies agree that thyroid homeostasis is the sensitive target. The fact that BMD results at this stage are lower than current exposure levels to PFHxS underscores the urgency of prioritizing endocrine end points in PFASs risk assessment.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"201 ","pages":"Article 115456"},"PeriodicalIF":3.9,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847632","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}
Hazim M. Ali , Amr A. Essawy , Ahmed Hamad Alanazi , Arafa Musa , Ahmed Emad F. Abbas , Ibrahim Bayoumi Abdel-Farid , Mohammed Gamal
{"title":"GC-MS and HPLC-FLD for sensitive assay of toxic cyclohexylamine in artificial sweetener tablets and human biological fluids","authors":"Hazim M. Ali , Amr A. Essawy , Ahmed Hamad Alanazi , Arafa Musa , Ahmed Emad F. Abbas , Ibrahim Bayoumi Abdel-Farid , Mohammed Gamal","doi":"10.1016/j.fct.2025.115447","DOIUrl":"10.1016/j.fct.2025.115447","url":null,"abstract":"<div><div>Cyclohexylamine (CHA) is a precursor in the synthesis of artificial sweeteners cyclamate and its major metabolite. CHA is toxic to the nervous system, kidneys, and liver in animal studies. In the present work, gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography-fluorescence detection (HPLC-FLD) were introduced for the first time to the determination of nano-level concentration of CHA in artificial sweetener tablets and human biological fluids. According to the obtained results, HPLC-FLD and GC-MS of CHA exhibit a wide linear range from 1 to 1250 ng/mL and 5–1500 ng/mL within limits of detection of 0.49 and 1.55 ng/mL, respectively. Furthermore, both chromatographic techniques exhibited high accuracy and precision, yielding recovery estimates ranging from 95.85 % to 100.70 % for the HPLC-FLD method and 91.54 %–99.64 % for the other while the corresponding values of relative standard deviation (RSD%) range from 0.25 to 0.82 % and 1.25–3.97 %. The accuracies for HPLC-FLD and GC-MS method in serum and urine samples are within the range of 90.29–99.94 %. On the other hand, CHA was detected in all studied artificial sweetener tablets, its level ranged from 1.35 to 102.64 ng/tablet. Also, the results obtained from the HPLC-FLD and GC-MS methods were statistically compared, and no significant difference was found.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"201 ","pages":"Article 115447"},"PeriodicalIF":3.9,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143838502","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}
Abdulaziz Arif A. Alshammari , Minhajul Arfeen , Abdullah Saleh Alkhamiss , Mai B. Alwesmi , Vasudevan Mani
{"title":"Montelukast's potential as a neuroprotective agent against acrylamide induced neurotoxicity: In vivo and computational modelling","authors":"Abdulaziz Arif A. Alshammari , Minhajul Arfeen , Abdullah Saleh Alkhamiss , Mai B. Alwesmi , Vasudevan Mani","doi":"10.1016/j.fct.2025.115448","DOIUrl":"10.1016/j.fct.2025.115448","url":null,"abstract":"<div><div>Tobacco consumption, a leading cause of over 8 million deaths annually, exposes individuals to acrylamide (ACY), a neurotoxin in cigarette smoke that disrupts neurotransmitter function and induces oxidative stress, contributing to neurodegeneration. This study evaluated neuroprotective potential of montelukast (MTLU), a leukotriene receptor antagonist with anti-inflammatory and antioxidant properties, against ACY-induced neurotoxicity. Cognitive performance was assessed using elevated plus maze, novel object recognition, and Y-maze tests over 14 days. Biomarkers associated with neurodegeneration (BACE1, GSK-3β, AChE), neuroinflammation (COX-2, PGE2, TNF-α, NF-κB), oxidative stress (GSH, MDA, CAT), and apoptosis (Bcl-2, Caspase-3, Bax) were analyzed. Histopathological analyses of brain tissues were conducted to examine structural damage, and computational studies provided additional support for selected in vivo findings. MTLU significantly ameliorated ACY-induced cognitive deficits and reduced levels of GSK-3β, AChE, COX-2, PGE2, TNF-α, NF-κB, MDA, Bax, and Caspase-3 while enhancing antioxidant defenses (GSH) and upregulating Bcl-2. Histopathological analysis confirmed reduced structural brain damage, and molecular docking indicated strong binding potential for MTLU with AChE, COX-2, GSK-3β, BACE-1, and Caspase-3. While these findings suggest a protective role for MTLU in mitigating ACY-induced cognitive impairments, oxidative stress, neuroinflammation, and apoptosis, further research is needed to confirm its therapeutic potential and clinical relevance.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"201 ","pages":"Article 115448"},"PeriodicalIF":3.9,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143834881","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}