Toxicology Mechanisms and Methods最新文献_第5页

Enhanced anti-cancer efficacy of Sorafenib and Pioglitazone via VEGF inhibition in DMBA-induced breast cancer model. 索拉非尼和吡格列酮通过抑制VEGF在dba诱导的乳腺癌模型中的抗癌作用。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2025-07-28 DOI: 10.1080/15376516.2025.2537889

Kinal Soni, Jigna Shah

{"title":"Enhanced anti-cancer efficacy of Sorafenib and Pioglitazone via VEGF inhibition in DMBA-induced breast cancer model.","authors":"Kinal Soni, Jigna Shah","doi":"10.1080/15376516.2025.2537889","DOIUrl":"10.1080/15376516.2025.2537889","url":null,"abstract":"Breast cancer remains the most prevalent cancer among women and a significant cause of mortality, partly due to treatment resistance and adverse effects. Sorafenib, a tyrosine kinase inhibitor, and Pioglitazone, a PPAR-γ agonist, exhibit anti-cancer properties. This study explores improved anti-cancer effects of combination of Sorafenib and Pioglitazone for breast cancer treatment. Protein-ligand molecular docking was performed to identify interactions of both drugs with various proteins. Cytotoxic effects of Sorafenib and Pioglitazone, individually and in combination, were evaluated on MCF-7 cells using MTT assay. DMBA-induced breast cancer model in female Sprague-Dawley rats assessed tumor volume, survival rates, oxidative stress markers, cytokines, tumor markers, and histopathology. Rats were divided into six groups, including control, individual treatments, combination therapy, and a doxorubicin standard group. Sorafenib demonstrated dose-dependent cytotoxicity. Pioglitazone exhibited limited cytotoxic effects when used alone but showed significant cytotoxicity when combined with Sorafenib. Combination therapy resulted in reduced tumor volume, enhanced survival rates, and restored body weight in DMBA-induced treatment animals. It significantly lowered oxidative stress parameters and pro-inflammatory cytokines, including IL-6, IL-1β, and TNF-α, as well as phosphorylated Akt levels. It inhibited tumor angiogenic markers VEGFR2 and VEGFR3 and promoted tumor suppressor p53 levels. Histopathological analysis confirms a reduction in tumor cell invasion and inflammation. The combination of Sorafenib and Pioglitazone exhibited enhanced anti-cancer effects by suppressing oxidative stress, inflammatory markers, pAkt, VEGF2, and VEGF3, as well as upregulating p53 levels, highlighting the promising potential of this combination for breast cancer treatment.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-20"},"PeriodicalIF":3.2,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

5-Hydroxymethylfurfural causes reproductive toxicity in male mice by increasing oxidative stress and apoptosis through the Nrf2/HO-1 signaling pathway. 5-羟甲基糠醛通过Nrf2/HO-1信号通路增加氧化应激和细胞凋亡，引起雄性小鼠生殖毒性。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2025-07-28 DOI: 10.1080/15376516.2025.2537319

Yasemin Aydin, Iremnur Sarialioglu, Gulsah Armut, Ertan Calmaz, Banu Orta Yilmaz

{"title":"5-Hydroxymethylfurfural causes reproductive toxicity in male mice by increasing oxidative stress and apoptosis through the Nrf2/HO-1 signaling pathway.","authors":"Yasemin Aydin, Iremnur Sarialioglu, Gulsah Armut, Ertan Calmaz, Banu Orta Yilmaz","doi":"10.1080/15376516.2025.2537319","DOIUrl":"10.1080/15376516.2025.2537319","url":null,"abstract":"5-Hydroxymethylfurfural (HMF) is a furan derivative compound commonly found in heat-treated carbohydrate-rich foods. Although its toxicological properties are well-studied, its effects on the male reproductive system at cellular and molecular levels remain unclear. This study is one of the first to evaluate the toxicity of HMF on the male reproductive system by conducting comprehensive analyses in both in vitro and in vivo models. In the in vitro model, TM3 Leydig cells were divided into four groups: control, 0.1, 1, and 10 mM HMF for 24 h. The study evaluated cell cytotoxicity and proliferation, oxidative stress levels, and antioxidant enzyme activity. The mRNA expression levels of oxidative stress- and apoptosis-related genes (Sod1, Gpx1, Nrf2, Ho1, Keap1, Bax, Bcl-2, Casp3, Trp53, and Parp1) were analyzed by RT-qPCR. In the in vivo model, BALB/c mice were divided into three groups: control, 30 mg/kg, and 300 mg/kg HMF administered orally for 21 days, and testicular tissues were evaluated with similar biochemical and genetic analyses. HMF significantly increased cytotoxicity, suppressed proliferation, and caused a significant increase in ROS levels in TM3 cells (p < 0.05). Moreover, HMF increased lipid peroxidation, suppressed antioxidant enzyme activities, and altered the expression of oxidative stress- and apoptosis-related genes in both TM3 cells and testicular tissue (p < 0.05). These statistically significant findings demonstrate that HMF induces oxidative damage and impairs cellular defense and survival mechanisms. In summary, our results highlight the potential reproductive risks associated with dietary HMF exposure and support the need for reassessing its toxicological safety limits.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-17"},"PeriodicalIF":3.2,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ontogenetic development of metabolic and detoxification genes in Seriola rivoliana larvae. 小孢子虫幼虫代谢和解毒基因的个体发育。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2025-07-17 DOI: 10.1080/15376516.2025.2534373

Danitzia A Guerrero-Tortolero, Rafael Campos-Ramos

{"title":"Ontogenetic development of metabolic and detoxification genes in Seriola rivoliana larvae.","authors":"Danitzia A Guerrero-Tortolero, Rafael Campos-Ramos","doi":"10.1080/15376516.2025.2534373","DOIUrl":"https://doi.org/10.1080/15376516.2025.2534373","url":null,"abstract":"The early larval stages in marine organisms have evolved to possess a genomic response ensuring survival and protection against environmental stressors, defined as the 'chemical defensome'. The larval fish defensome consists of genes transcribed and upregulated after hatching to form detoxification proteins, catalyzing enzymes, transporters, transcription factors, and antioxidant proteins. Therefore, we aimed to analyze the timing of transcription and upregulation of metabolic, protective and detoxification genes during the ontogenetic development in Seriola rivoliana larvae up to the onset of exogenous feeding. Larvae samples from each experimental replicate were taken after hatching (day zero), day one (24 h post-hatching), day two (48 h post-hatching), day three (72 h post-hatching), and day four (96 h post-hatching). We used RNA-seq followed by gene annotation to identify these genes and to evaluate differential gene expression. From day one after hatching, results showed the upregulation of cytochrome P450 and other genes that coded for enzymes capable of bio-transform xenobiotic compounds such as reductases, hydrolases, transferases and dehydrogenases. Additionally, a set of genes of the superfamily of ATP-binding cassette transporters became upregulated for cholesterol homeostasis and many others involved in detoxification and multidrug resistance of xenobiotics. We also analyzed genes involved in stress-responses (transcription factors) and genes that code for antioxidants proteins. However, none of them showed differential expression. Our study suggests an orchestrated and organized ontogenetic sequential upregulation of the defensome as a natural process to adapt to the environment, the regulation process of macronutrients, and a defensive metabolic response in case of encountering harmful xenobiotic compounds or toxins in food and water at the onset of exogenous feeding, which contributes to the understanding of the chemical defensome in early marine larval development.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-15"},"PeriodicalIF":3.2,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In vitro effects of environmentally relevant concentrations of nonylphenol and selected pyrethroid metabolites on a mouse sertoli cell line (TM4). 壬基酚和拟除虫菊酯代谢物的环境相关浓度对小鼠支持细胞系（TM4）的体外影响。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2025-07-10 DOI: 10.1080/15376516.2025.2528100

Nthabiseng Kgabele Matjomane, Lisa Repsold, Sean Mark Patrick, Magdalena Catherina van Zijl, Michelle Helen Visagie, Natalie Hildegard Aneck-Hahn

{"title":"In vitro effects of environmentally relevant concentrations of nonylphenol and selected pyrethroid metabolites on a mouse sertoli cell line (TM4).","authors":"Nthabiseng Kgabele Matjomane, Lisa Repsold, Sean Mark Patrick, Magdalena Catherina van Zijl, Michelle Helen Visagie, Natalie Hildegard Aneck-Hahn","doi":"10.1080/15376516.2025.2528100","DOIUrl":"10.1080/15376516.2025.2528100","url":null,"abstract":"Advances in the chemical industry and increased environmental pollution have contributed to declining reproductive health. Many pollutants act as endocrine-disrupting chemicals (EDCs), with (anti-)estrogenic and (anti-)androgenic properties that disrupt hormonal balance and contribute to male reproductive dysfunction. Mouse Sertoli cells, which closely resemble human Sertoli cells, are targets for various environmental contaminants, making the cell line an ideal model for male reproductive toxicological studies. Sertoli cells (TM4) were exposed to environmentally relevant concentrations of EDCs, including cypermethrin, deltamethrin, rac-trans permethrinic acid, 3-phenoxybenzoic acid and para-nonylphenol (p-NP), for 24 h in vitro. Cytotoxicity was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, oxidative stress via an intracellular total reactive oxygen species (ROS) activity assay kit, and morphological changes via hematoxylin & eosin staining. The MTT assay revealed a moderate decrease (approximately 20% cell death) in cell viability. ROS levels were significantly higher in EDC-treated cells than in controls, with small effect sizes confirmed through Cohen's d analysis. Morphological changes, including membrane elongation, cytoplasmic vesicles, and reduced cell density, were most pronounced in p-NP-exposed cells. These findings suggest that exposure to pyrethroids and nonylphenol may induce toxicity in mouse Sertoli cells.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-10"},"PeriodicalIF":3.2,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144561256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Behavioral pharmacology and toxicology of dimethyl sulfoxide in artemia nauplii: vehicle or positive control? 二甲基亚砜对青蒿的行为药理学和毒理学：载体还是阳性对照？

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2025-07-08 DOI: 10.1080/15376516.2025.2527160

Areeha Khalid, Matthew Pytynia, Sheila Cazares, Desiree K Batangan, Cassandra Repole, Andrew B Hawkey

{"title":"Behavioral pharmacology and toxicology of dimethyl sulfoxide in artemia nauplii: vehicle or positive control?","authors":"Areeha Khalid, Matthew Pytynia, Sheila Cazares, Desiree K Batangan, Cassandra Repole, Andrew B Hawkey","doi":"10.1080/15376516.2025.2527160","DOIUrl":"10.1080/15376516.2025.2527160","url":null,"abstract":"Dimethyl sulfoxide (DMSO) is a routinely used solvent in toxicology studies that are focused on toxicants with low natural solubility in water. However, prior research suggests that DMSO can alter neurological and behavioral outcomes under some circumstances, which could affect its suitability for neurotoxicology research. The current study evaluated the suitability of DMSO vehicles in an aquatic invertebrate model, Artemia nauplii. Subjects were exposed to solutions of 0.01-1% DMSO and assessed for mortality, motility, morphology, and recovery. In Experiment 1, 1-hr exposures significantly decreased swimming speed and increased rotation rates (0.01%, 1%) (slow, spiral swimming). In Experiment 2, 48-hr exposures suppressed swimming speed (0.1%, 1%), and path rotation (1%) (slower, non-spiral swimming), as well as body length (1%). In Experiment 3, following either 1-hr or 48-hr exposures to 1% DMSO, swimming speed and rotation rate persisted through 4-hr post-treatment, and recovered after a 24-hr washout period. Our results indicate that DMSO does affect motility and related behaviors in Artemia after 1- or 48-hr exposures, that these effects are reversible, and that progressive exposure to DMSO can alter the profile of effects. Consideration must be taken when determining what solvent to use when studying toxicants in aquatic species like Artemia.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-19"},"PeriodicalIF":3.2,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evaluation of polyethylene microplastics toxicity using Nrf2/ARE and MAPK/Nrf2 signaling pathways. 利用Nrf-2/ARE信号通路评价聚乙烯微塑料的毒性。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2025-07-06 DOI: 10.1080/15376516.2025.2527154

Mennatallah Mahmoud Ahmed Mohamed, Nada A Yousri, Noura Hassan Khamis, Shimaa Abdel Baset Abdel Hakim, Samar Hisham Elsayed, Elzahraa Ahmed Elrefaie Ali

{"title":"Evaluation of polyethylene microplastics toxicity using Nrf2/ARE and MAPK/Nrf2 signaling pathways.","authors":"Mennatallah Mahmoud Ahmed Mohamed, Nada A Yousri, Noura Hassan Khamis, Shimaa Abdel Baset Abdel Hakim, Samar Hisham Elsayed, Elzahraa Ahmed Elrefaie Ali","doi":"10.1080/15376516.2025.2527154","DOIUrl":"10.1080/15376516.2025.2527154","url":null,"abstract":"Microplastics (MPs) have emerged as a serious global environmental threat due to their resistance to degradation and persistence in ecosystems. Given their potential risks to human health, it is essential to thoroughly investigate the mechanisms of toxicity and associated health consequences. This study examined the toxicological and reproductive effects of varying doses of polyethylene microplastics (PE-MPs) in 120 male and female Sprague Dawley rats. A statistically significant, dose-dependent increase in malondialdehyde levels was observed, along with a reduction in catalase activity. Furthermore, alterations were detected in sexual hormone levels and disruptions were noted in both the Kelch-like ECH-associated protein 1 (Keap1)-Nrf2-ARE (antioxidant response element) and p38 MAPK-Nrf2 signaling pathways. PE-MP exposure also produced marked histopathological changes in the testes and ovaries. These findings indicate that reproductive toxicity from PE-MPs is associated with impairments in the Keap1-Nrf2-ARE and p38 MAPK-Nrf2 pathways. The results underscore the importance of limiting MP exposure to mitigate potential health hazards and provide new data on the potential mechanisms of toxicity of MPs.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-20"},"PeriodicalIF":3.2,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The effect of simvastatin induced neurotoxicity on mitochondrial function in human neuronal cells. 辛伐他汀诱导的神经毒性对人神经元细胞线粒体功能的影响。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2025-07-01 Epub Date: 2025-03-03 DOI: 10.1080/15376516.2025.2471807

Lauren Millichap, Nadia Turton, Razan Alomosh, Robert A Heaton, Amy Bateman, Nasser Al-Shanti, Adam P Lightfoot, Elisabetta Damiani, Fabio Marcheggiani, Patrick Orlando, Sonia Silvestri, Luca Tiano, Iain P Hargreaves

{"title":"The effect of simvastatin induced neurotoxicity on mitochondrial function in human neuronal cells.","authors":"Lauren Millichap, Nadia Turton, Razan Alomosh, Robert A Heaton, Amy Bateman, Nasser Al-Shanti, Adam P Lightfoot, Elisabetta Damiani, Fabio Marcheggiani, Patrick Orlando, Sonia Silvestri, Luca Tiano, Iain P Hargreaves","doi":"10.1080/15376516.2025.2471807","DOIUrl":"10.1080/15376516.2025.2471807","url":null,"abstract":"3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (HMGR) inhibitors, commonly known as statins, are drugs frequently used in the treatment of hypercholesterolemia and hyperlipidemia. However, the current study has demonstrated that simvastatin induces neurotoxicity and is associated with cellular coenzyme Q10 (CoQ10) depletion. CoQ10 has a significant role in the mitochondrial electron transport chain (ETC), in addition to being a fundamental lipid-soluble antioxidant. Depletion of CoQ10 is frequently associated with impaired mitochondrial function and increased oxidative stress. The aim of this study was to investigate the potential mechanisms of simvastatin-induced neurotoxicity assessing mitochondrial function and evidence of oxidative stress in an in vitro SH-SY5Y human neuronal cell line. Fluorescence studies assessed via flow cytometry determined significant increases in intracellular and mitochondrial reactive oxygen species production following SH-SY5Y treatment with simvastatin compared to control cells. Additionally, spectrophotometric enzyme studies determined a significant (p < 0.0001) inhibition of ETC complex I and II-III activities which accompanied a significant decrease in neuronal CoQ10 content (p < 0.005) and cell viability (p < 0.0001). The results of the present study have indicated evidence of mitochondrial dysfunction and increased oxidative stress, resulting in increased loss of neuronal viability following simvastatin treatment. Thus, these results demonstrate evidence of neurotoxicity associated with statin therapy.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"592-603"},"PeriodicalIF":3.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neodymium nitrate promotes the apoptosis of mouse liver cells via Bcl2l1/Caspase 3 pathway. 硝酸钕通过Bcl2l1/Caspase 3途径促进小鼠肝细胞凋亡。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2025-07-01 DOI: 10.1080/15376516.2025.2501253

Jing Leng, Ning Wang, Xiu-Li Chang, Xiao-Peng Zhang, Jing Xu, Zheng-Li Yang, Ke-Lei Qian, Zhi-Qing Zheng, Gong-Hua Tao, Xu-Dong Jia, Ping Xiao, Xin-Yu Hong

{"title":"Neodymium nitrate promotes the apoptosis of mouse liver cells via Bcl2l1/Caspase 3 pathway.","authors":"Jing Leng, Ning Wang, Xiu-Li Chang, Xiao-Peng Zhang, Jing Xu, Zheng-Li Yang, Ke-Lei Qian, Zhi-Qing Zheng, Gong-Hua Tao, Xu-Dong Jia, Ping Xiao, Xin-Yu Hong","doi":"10.1080/15376516.2025.2501253","DOIUrl":"10.1080/15376516.2025.2501253","url":null,"abstract":"Background: Neodymium, as a strategic rare earth element (REE), has demonstrated bioaccumulative potential and can permeate human systems through inhalation of airborne particulates, ingestion of contaminated food/water, and dermal absorption from soil matrices, ultimately eliciting multi-organ toxicological manifestations. However, the hepatotoxicological profile of neodymium species and their pathophysiological mechanisms remain inadequately characterized. Neodymium nitrate (Nd(NO3)3), the predominant water-soluble neodymium species, exhibits marked bioavailability with particular hepatic tropism.Objective: This study aims to investigate the effects of neodymium nitrate on apoptosis of mouse liver cells and its underlying molecular mechanisms.Results: Mouse liver cell line AML12 was treated with gradient concentrations of neodymium nitrate. The results showed that neodymium nitrate inhibited liver cell proliferation, induced apoptosis, and exhibited a dose-dependent relationship. Western blotting and quantitative real-time PCR (qRT-PCR) revealed that neodymium nitrate suppressed Bcl2l1 transcription and activated the proteolysis of Caspase 3. To further explore the molecular mechanism, Bcl2l1 protein was overexpressed in mouse liver cells. The findings indicated that overexpression of Bcl2l1 rescued neodymium nitrate-induced apoptotic phenotypes and attenuated Caspase 3 cleavage.Conclusion: The present data suggest that neodymium nitrate induces apoptosis of mouse liver cells through the Bcl2l1/Caspase 3 pathway. However, further studies are called for to substantiate this view, as the findings may provide critical mechanistic evidence for revising the toxicological risk assessment frameworks of rare earth elements.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-10"},"PeriodicalIF":3.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

New mechanistic approach of TiCN film-coated NiTi substrate toxicity: impairment in mitochondrial electron transfer in diabetic rat tooth gum cells. TiCN膜包覆NiTi底物毒性的新机制研究：糖尿病大鼠牙牙龈细胞线粒体电子转移损伤。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2025-07-01 Epub Date: 2025-04-28 DOI: 10.1080/15376516.2025.2479000

Abbas Razmi, Enayatollah Seydi, Behnaz Ashtari, Ali Neshasteh-Riz, Parvaneh Naserzadeh

{"title":"New mechanistic approach of TiCN film-coated NiTi substrate toxicity: impairment in mitochondrial electron transfer in diabetic rat tooth gum cells.","authors":"Abbas Razmi, Enayatollah Seydi, Behnaz Ashtari, Ali Neshasteh-Riz, Parvaneh Naserzadeh","doi":"10.1080/15376516.2025.2479000","DOIUrl":"10.1080/15376516.2025.2479000","url":null,"abstract":"In recent years, researchers have focused on using new materials for screws in bone jaw tissue replacement. However, concerns regarding the cytotoxicity and biocompatibility of these materials for cells remain a subject of ongoing discussion. In this study, a novel implant for bone jaw tissue regeneration was fabricated by depositing the titanium carbo-nitride (TiCN) film on NiTi shape memory alloy substrate using the Cathodic Arc Physical Vapor Deposition (CAPVD) technique. Our study emphasized positive cellular responses of TiCN-coated NiTi substrate on diabetic rat tooth gum cells for 1, 15, and 30 days. Initially, the evaluation focused on the characterization and distribution of NiTi alloy in tissues. Then, the levels of factors such as components of White Blood Cells (WBC), ATP, oxidative stress parameters, cytochrome c release and damage to the lysosomal membrane were evaluated in all groups. The results indicated that in the group of diabetic rats with TiCN-coated NiTi substrate, the level of oxidative stress parameters decreased. In addition, the cell viability, glutathione (GSH) intracellular and ATP increased and the rate of cytochrome c release, and damage to the lysosome membrane decreased. It can be concluded that the TiCN-coated NiTi screw is a promising material for bone jaw tissue replacement in diabetic patients due to its low cytotoxicity.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"633-643"},"PeriodicalIF":3.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cytotoxic potential of an indole-conjugated Oleanolic acid analogue: suppression of NSCLC proliferation through modulation of mitochondrial apoptotic dynamics. 吲哚共轭齐墩果酸类似物的细胞毒性潜力：通过调节线粒体凋亡动力学抑制非小细胞肺癌增殖。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2025-07-01 Epub Date: 2025-03-25 DOI: 10.1080/15376516.2025.2481915

Srividya Subramanian, Sankar Pajaniradje, Suhail Ahmad Bhat, Sathyapriya Chandramohan, Parthiban Anaikutti, Rukkumani Rajagopalan

{"title":"Cytotoxic potential of an indole-conjugated Oleanolic acid analogue: suppression of NSCLC proliferation through modulation of mitochondrial apoptotic dynamics.","authors":"Srividya Subramanian, Sankar Pajaniradje, Suhail Ahmad Bhat, Sathyapriya Chandramohan, Parthiban Anaikutti, Rukkumani Rajagopalan","doi":"10.1080/15376516.2025.2481915","DOIUrl":"10.1080/15376516.2025.2481915","url":null,"abstract":"Pre-clinical toxicological investigations are pivotal in the development of safer and more efficacious chemotherapeutic agents. Oleanolic acid (OA), a naturally occurring pentacyclic triterpenoid, has demonstrated anticancer potential but is often limited by the toxic side effects of its derivatives. In the current study, we carried out the facile synthesis of a modified OA analogue, OD2, and studied its cytotoxicity and efficacy analysis across several cell lines. Mechanistic toxicology was explored through fluorescence-based assays. Annexin-V/Propidium Iodide (A-V/PI) staining and TUNEL assays were used to confirm apoptosis. OD2 exhibited dose-dependent cytotoxicity, with a pronounced effect on A549 lung cancer cells compared to other cancerous and non-cancerous cell lines. Apoptosis was found to be the predominant mode of cell death, evidenced by Fluorescence imaging analysis of chromatin condensation and mitochondrial dysfunction. This was further validated by an increase in Annexin-V-positive and TUNEL-positive cells in treated groups. OD2 activated the intrinsic mitochondrial apoptotic pathway as evidenced by increased Bax and decreased Bcl-2 protein abundance levels. While the current study showcases the therapeutic potential of the selective toxicological activity of OD2, future studies will focus on the deconvolution of its potential polypharmacological mode of action and decoding the basis of its selective action, so as to glean important lessons that can be applied in the development of chemotherapeutic agents with favorable toxicological profiles.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"668-681"},"PeriodicalIF":3.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0