Toxicology Research最新文献

{"title":"SARM1 in the pathogenesis of immune-related disease.","authors":"Yihan Ye, Fuyong Song","doi":"10.1093/toxres/tfae208","DOIUrl":"10.1093/toxres/tfae208","url":null,"abstract":"<p><strong>Background: </strong>Sterile alpha and toll interleukin receptor motif-containing protein 1 (SARM1) are primarily expressed in the mammalian nervous system, with their presence in neurons being associated with mitochondrial aggregation. SARM1 functions as a mediator of cell death and morphological changes, while also regulating Waller degeneration in nerve fibers and influencing glial cell formation.</p><p><strong>Purpose: </strong>Recent reports demonstrate SARM1 serves as a connector in the Toll-like receptor (TLR) pathway and plays a role in regulating inflammation during periods of stress such as infection, trauma, and hypoxia. These findings offer new insights into pathogenesis research and the prevention and treatment of neurodegenerative diseases and pathogen infections.</p><p><strong>Methods: </strong>This review synthesizes recent findings on the immune-related mechanisms of SARM1, emphasizing its roles in inflammation and its functional impact on the nervous system and other bodily systems.</p><p><strong>Conclusions: </strong>Understanding the multifaceted roles of SARM1 in immune regulation and neuronal health provides novel insights into its involvement in disease pathogenesis. These insights hold promise for advancing research into the prevention and treatment of neurodegenerative diseases and pathogen-induced conditions.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 6","pages":"tfae208"},"PeriodicalIF":2.2,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811591","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":"Cancer-associated fibroblasts affect breast cancer cell sensitivity to chemotherapeutic agents by regulating NRBP2.","authors":"Xiaoyan Jin, Yong Chen, Gui Wang","doi":"10.1093/toxres/tfae204","DOIUrl":"10.1093/toxres/tfae204","url":null,"abstract":"<p><strong>Objective: </strong>To uncover the role of nuclear receptor-binding protein 2 (NRBP2) in cancer-associated fibroblasts (CAFs), and CAFmediated TAM sensitivity in breast cancer (BC).</p><p><strong>Methods: </strong>10 pairs of matched tumor tissues and adjacent normal tissues were collected and CAFs and normal fibroblasts (NFs) were isolated. CCK-8 as well as colony formation assays showed the effects on cell growth. qPCR and Immunoblot showed the expression of NRBP2 in CAFs. FCM as well as Immunoblot assays exhibited the effects on cell apoptosis. Immunoblot further confirmed the mechanism.</p><p><strong>Results: </strong>CAFs contributed to BC cell growth. In addition, the expression of NRBP2 is downregulated in CAFs. NRBP2 suppressed CAF-induced resistance in BC cells. Further, NRBP2 expression in CAF group increased TAM induced apoptosis. Mechanically, NRBP2 in CAFs inhibited Akt pathway, therefore suppressed resistance in BC cells.</p><p><strong>Conclusion: </strong>CAFs affected BC cell sensitivity to TAM by regulating NRBP2.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 6","pages":"tfae204"},"PeriodicalIF":2.2,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811512","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":"Ferulic acid improves palmitate-induced insulin resistance by regulating IRS-1/Akt and AMPK pathways in L6 skeletal muscle cells.","authors":"Jae Eun Park, Ji Sook Han","doi":"10.1093/toxres/tfae197","DOIUrl":"10.1093/toxres/tfae197","url":null,"abstract":"<p><strong>Objective: </strong>Increased plasma-free fatty acid (FFA) induced by obesity can trigger insulin resistance and it is a significantly dangerous constituent in the progression of diabetes. Although ferulic acid has various physiological functions, no studies have examined ferulic acid's effects on insulin-resistant muscle cells. This study investigated the effect of ferulic acid on improving palmitic acid-induced insulin resistance in L6 skeletal muscle cells.</p><p><strong>Methods: </strong>Palmitic acid induces insulin resistance by inhibiting the phosphorylation of IRS-1_tyr and stimulating the phosphorylation of IRS-1_ser in diabetes. Thus, palmitic acid (0.75 mM) was used as an insulin resistance inducer and ferulic acid was treated at various concentrations (2, 5, 10, and 20 uM) in L6 skeletal muscle cells.</p><p><strong>Results: </strong>Palmitic acid significantly reduced the cell viability of L6 skeletal muscle cells, whereas ferulic acid treatment significantly increased cell viability in a concentration-dependent manner. Palmitic acid significantly reduced glucose uptake due to insulin resistance in the muscle cells; however, ferulic acid treatment remarkably increased glucose uptake. Ferulic acid promoted the phosphorylation of IRS-1_tyr that palmitic acid inhibited, while also suppressing the palmitic acid-induced phosphorylation of IRS-1_ser. Ferulic acid activated PI3K and then stimulated the phosphorylation of Akt, which increased PM-GLUT4 expression, thereby stimulating glucose uptake into insulin-resistant muscle cells. Ferulic acid also increased glycogen synthesis by phosphorylating GSK3β via the Akt pathway. Additionally, ferulic acid significantly promoted phosphorylation of AMPK, enhancing PM-GLUT4 levels and glucose uptake.</p><p><strong>Conclusions: </strong>These results suggest that ferulic acid may improve palmitate-induced insulin resistance by regulating IRS-1/ Akt and the AMPK pathway in L6 skeletal muscle cells.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 6","pages":"tfae197"},"PeriodicalIF":2.2,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811519","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":"Optimization of concentrations and exposure durations of commonly used positive controls in the in vitro alkaline comet assay.","authors":"Seda İpek Tekneci, Aylin Üstündağ, Yalçın Duydu","doi":"10.1093/toxres/tfae195","DOIUrl":"10.1093/toxres/tfae195","url":null,"abstract":"<p><p>Endogenous and exogenous factors cause DNA damage through chemical changes in the genomic DNA structure. The comet assay is a versatile, rapid, and sensitive method for evaluating DNA integrity at the individual cell level. It is used in human biomonitoring studies, the identification of DNA lesions, and the measurement of DNA repair capacity. Despite its widespread application, variations between studies remain problematic, often due to the lack of a common protocol and appropriate test controls. Using positive controls is essential to assess inter-experimental variability and ensure reliable results. Hydrogen peroxide (H₂O₂) is the most commonly used positive control, while potassium bromate (KBrO₃), methyl methanesulfonate (MMS), ethyl methanesulfonate (EMS), <i>N</i>-ethyl-<i>N</i>-nitrosourea (ENU), and etoposide are used less frequently. However, differences in concentrations and exposure durations prevent the confirmation of test method efficacy. This study investigates the dose-response relationship for H₂O₂, KBrO₃, MMS, EMS, ENU and etoposide in the comet assay for 30 and 60-minute exposure durations in 3T3 cell lines. Accordingly recommended concentrations and exposure durations were found to be 50 μM 30 minutes (H₂O₂); 500 μM 60 min. (MMS); 10 μM 30 min. (Etoposide); 0.2 mM 30 min. and 2 mM 60 min. (EMS); 2 mM 30 min. (ENU); 500 μM 30 min. and 50 μM 60 min. (KBrO₃). Our findings will contribute to reducing inter-laboratory variability by offering guidance on selecting doses and exposure durations for positive controls in the <i>in vitro</i> alkaline comet assay.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 6","pages":"tfae195"},"PeriodicalIF":2.2,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805656","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":"Impact of micro-nano plastics in daily life on human health: toxicological evaluation from the perspective of normal tissue cells and organoids.","authors":"Jie Wang, Lan-Gui Xie, Xian-Fu Wu, Zong-Ge Zhao, Yong Lu, Hui-Min Sun","doi":"10.1093/toxres/tfae205","DOIUrl":"10.1093/toxres/tfae205","url":null,"abstract":"<p><p>Plastics are the most frequently used materials in people's daily life, and the primary and secondary microplastics generated from them may harm the health of adults. This paper focuses on the summary of the existence of microplastics in many objects most closely related to people in daily life, the toxicological influences it causes in cultured human normal cells and organoids, and the prospects for future research directions. Micro- and nano-plastics (MNPs) are found in almost all of our everyday products, such as food, drink, and daily necessities, etc. It can enter the digestive tract, respiratory system, and body fluids of the human body, and at lower or equal environment concentrations exhibits obvious cytotoxicity and genotoxicity toward cells and organoids, probably becoming a kind of toxin affecting human health. In addition, due to MNPs can be transferred from the placenta to the embryo, long-term growth-tracking studies of newborns should be done vitally. Besides, due to their wide usability in daily products and the ability to penetrate cytomembranes, the toxicological effects of polyethylene and polypropylene nanoplastic particles equal to or lower than environmental (normal exposure to human body) concentrations are recommended to be studied on human health in the future. Finally, for those individuals who carry MNPs, long-term health evaluation must be performed.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 6","pages":"tfae205"},"PeriodicalIF":2.2,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11645661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826762","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":"Predicting the molecular mechanisms of cardiovascular toxicity induced by per- and polyfluoroalkyl substances: an In Silico network toxicology perspective.","authors":"Fuat Karakuş, Burak Kuzu","doi":"10.1093/toxres/tfae206","DOIUrl":"10.1093/toxres/tfae206","url":null,"abstract":"<p><strong>Background: </strong>Per- and polyfluoroalkyl substances (PFAS) are human-made chemicals that accumulate in the human body and the environment over time. Humans are primarily exposed to PFAS through drinking water, food, consumer products, and dust. These exposures can have many adverse health effects, including cardiovascular diseases (CVDs) and factors contributing to CVDs. This study identified the molecular mechanisms of CVDs caused by PFAS.</p><p><strong>Methods: </strong>For this purpose, various computational tools, such as the Comparative Toxicogenomic Database, ShinyGO, ChEA3, MIENTURNET, GeneMANIA, STRING, and Cytoscape, were used to conduct in silico analyses.</p><p><strong>Results: </strong>The results showed that 10 genes were common between PFAS and CVDs, and among these common genes, the PPAR signaling pathway, fatty acid metabolic processes, and lipid binding were the most significantly associated gene ontology terms. Among the top 10 transcription factors (TFs) related to these common genes, peroxisome proliferator-activated receptor gamma and androgen receptor were the most prominent. Additionally, hsa-miR-130b-3p, hsa-miR-130a-3p, and hsa-miR-129-5p were featured microRNAs involved in PFAS-induced CVDs. Finally, <i>PPARA</i> and <i>PPARG</i> were identified as core genes involved in PFAS-induced CVDs.</p><p><strong>Conclusion: </strong>These findings may contribute to a better understanding of the molecular mechanisms and reveal new potential targets in PFAS-induced CVDs.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 6","pages":"tfae206"},"PeriodicalIF":2.2,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11645662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826794","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":"The impact of Benzophenone-3 on osteoarthritis pathogenesis: a network toxicology approach.","authors":"Yongji Li, Geqiang Wang, Peiran Liu, Lin Zhang, Hai Hu, Xiangjun Yang, Hongpeng Liu","doi":"10.1093/toxres/tfae199","DOIUrl":"10.1093/toxres/tfae199","url":null,"abstract":"<p><strong>Background: </strong>Arthritis is a degenerative joint disease influenced by various environmental factors, including exposure to Benzophenone-3 (BP3), a common UV filter. This study aims to elucidate the toxicological impact of BP3 on arthritis pathogenesis using network toxicology approaches.</p><p><strong>Method: </strong>We integrated data from the Comparative Toxicogenomics Database (CTD) and Gene Expression Omnibus (GEO) to identify differentially expressed BP3-related toxicological targets in osteoarthritis (OA). Enrichment analyses were conducted to determine the implicated biological processes, cellular components, and molecular functions. Further, the involvement of the PI3K-Akt signaling pathway was investigated, along with correlations with immune cell infiltration and immune-related pathways. Molecular docking analysis was performed to examine BP3 interactions with key PI3K-Akt pathway proteins.</p><p><strong>Results: </strong>A total of 74 differentially expressed BP3-related targets were identified. Enrichment analysis revealed significant pathways, including PI3K-Akt, MAPK, and HIF-1 signaling. The PI3K-Akt pathway showed notable dysregulation in OA, with reduced activity and differential expression of key genes such as ANGPT1, ITGA4, and PIK3R1. Correlation analysis indicated significant associations between PI3K-Akt pathway activity and various immune cell types and immune pathways. Molecular docking highlighted strong interactions between BP3 and proteins like AREG, suggesting potential disruptions in signaling processes.</p><p><strong>Conclusions: </strong>BP3 exposure significantly alters the expression of toxicological targets and disrupts the PI3KAkt signaling pathway, contributing to OA pathogenesis. These findings provide insights into the molecular mechanisms of BP3-induced OA and identify potential therapeutic targets for mitigating its effects.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 6","pages":"tfae199"},"PeriodicalIF":2.2,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11645663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826798","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":"Nanoliposomal system for augmented antibacterial and antiproliferative efficacy of <i>Melissa officinalis</i> L. extract.","authors":"Nagihan Nizam, Gokce Taner, Munevver Muge Cagal","doi":"10.1093/toxres/tfae198","DOIUrl":"10.1093/toxres/tfae198","url":null,"abstract":"<p><strong>Objective: </strong>This study focused on the nanoliposomal encapsulation of bioactive compounds extracted from <i>Melissa officinalis</i> L. (ME) using ethanol as a strategy to improve the antibacterial activity, anticytotoxic, and antiproliferative properties.</p><p><strong>Methods: </strong>Nanoliposomes loaded with ME (MEL) were characterized for total phenolic content, particle size, polydispersity, and encapsulation efficiency. The minimum inhibitory concentration (MIC) values for MEL and ME were determined to evaluate antibacterial activity. To examine the toxicity profiles of ME and MEL, tests were conducted on the A549 and BEAS-2B cell lines using the MTT assay. Furthermore, an <i>in vitro</i> sctrach assay was conducted to evaluate the antiproliferative effects of ME and MEL on A549 cells.</p><p><strong>Results: </strong>Nanoliposomes presented entrapment efficiency higher than 80%, nanometric particle size, and narrow polydispersity. The MIC values for MEL and ME were observed as 93.75 μg/μL against E. coli. MIC values for MEL and ME were achieved as 4.68 μg/μL and 9.375 μg/mL against S. aureus, respectively. The IC50 values for ME were determined to be 1.13 mg/mL and 0.806 mg/mL, while the IC50 values for MEL were found to be 3.5 mg/mL and 0.868 mg/mL on A549 and BEAS-2B cell lines, respectively. Additionally, The MEL showed an antiproliferative effect against A549 cells at 500 μg/mL concentration.</p><p><strong>Conclusion: </strong>All experimental findings unequivocally demonstrate that the novel nanoliposomal system has effectively augmented the antibacterial activities and antiproliferative effects of ME. The initial findings indicate that nanoliposomes could effectively serve as carriers for ME in pharmaceutical applications.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 6","pages":"tfae198"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11645532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826763","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":"Comparative study of cytotoxic Signaling pathways in H1299 cells exposed to alternative Bisphenols: BPA, BPF, and BPS.","authors":"Ji-Young Kim, Geun-Seup Shin, Mi-Jin An, Hyun-Min Lee, Ah-Ra Jo, Yuna Park, Jinho Kim, Yujeong Hwangbo, Chul-Hong Kim, Jung-Woong Kim","doi":"10.1093/toxres/tfae200","DOIUrl":"10.1093/toxres/tfae200","url":null,"abstract":"<p><strong>Background: </strong>Bisphenols are prevalent in food, plastics, consumer goods, and industrial products. Bisphenol A (BPA) and its substitutes, bisphenol F (BPF) and bisphenol S (BPS), are known to act as estrogen mimics, leading to reproductive disorders, disruptions in fat metabolism, and abnormalities in brain development.</p><p><strong>Objectives: </strong>Despite numerous studies exploring the adverse effects of bisphenols both <i>in vitro</i> and <i>in vivo</i>, the molecular mechanisms by which these compounds affect lung cells remain poorly understood. This study aims to compare the effects of BPA, BPF, and BPS on the physiological behavior of human nonsmall cell lung cancer (NSCLC) cells.</p><p><strong>Materials and methods: </strong>Human non-small cell lung cancer (NSCLC) H1299 cells were treated with various concentration of BPA, BPF and BPS during different exposure time. Cellular physiology for viability and cell cycle was assessed by the staining with apoptotic cell makers such as active Caspase-3 and cyclins antibodies. Toxicological effect was quantitatively counted by using flow-cytometry analysis.</p><p><strong>Results: </strong>Our findings indicate that BPA induces apoptosis by increasing active Caspase-3 levels in H1299 cells, whereas BPF and BPS do not promote late apoptosis. Additionally, BPA was found to upregulate cyclin B1, causing cell cycle arrest at the G0/G1 phase and leading to apoptotic cell death through Caspase-3 activation. Conclusion: These results demonstrate that BPA, BPF, and BPS differentially impact cell viability, cell cycle progression, and cell death in human NSCLC cells.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 6","pages":"tfae200"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11645530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826759","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":"Role of vitamin D₃ in mitigating sodium arsenite-induced neurotoxicity in male rats.","authors":"Heba Mohamed Abdou, Alaa Mohamed Saad, Heba-Tallah Abd Elrahim Abd Elkader, Amina E Essawy","doi":"10.1093/toxres/tfae203","DOIUrl":"10.1093/toxres/tfae203","url":null,"abstract":"<p><p>Arsenic is associated with various neurological disorders, notably affecting memory and cognitive functions. The current study examined the protective effects of vitamin D₃ (Vit. D₃) in countering oxidative stress, neuroinflammation and apoptosis induced by sodium arsenite (SA) in the cerebral cortex of rats. Male Wistar rats were subjected to a daily oral administration of sodium arsenite (NaAsO₂, SA) at a dosage of 5 mg/kg, along with 500 IU/kg of Vit. D₃, and a combination of both substances for four weeks. The results indicated that Vit. D₃ effectively mitigated the SA-induced increase in oxidative stress markers, thiobarbituric acid reactive substances (TBARS) and nitric oxide (NO), the decrease in antioxidants (reduced glutathione; GSH, superoxide dismutase; SOD, catalase; CAT, and glutathione peroxidase; GPx), as well as the increase in pro-inflammatory markers including, tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and amyloid-beta (Aβ)1-42. Furthermore, Vit. D₃ reversed the alterations in the neurochemicals acetylcholinesterase (AchE), monoamine oxidase (MAO), dopamine (DA), and acetylcholine (Ach) and ameliorated the histopathological changes in the cerebral cortex. Moreover, immunohistochemical analyses revealed that Vit. D₃ reduced the SA-induced overexpression of cerebral cysteine aspartate-specific protease-3 (caspase-3) and glial fibrillary acidic protein (GFAP) in the cerebral cortex of male rats. Consequently, the co-administration of Vit. D₃ can protect the cerebral cortex against SA-induced neurotoxicity, primarily through its antioxidant, anti-inflammatory, anti-apoptotic, and anti-astrogliosis effects.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 6","pages":"tfae203"},"PeriodicalIF":2.2,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11602150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749453","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}