Toxicology Mechanisms and Methods最新文献_第10页

The investigation of the toxicity of organophosphorus flame retardants (OPFRs) by using in silico toxicity prediction platform ProTox- 3.0. 利用硅学毒性预测平台 ProTox- 3.0 研究有机磷阻燃剂 (OPFR) 的毒性。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2025-01-01 Epub Date: 2024-07-25 DOI: 10.1080/15376516.2024.2382815

Priyanka Banerjee, Onur Ulker, Irem Ozkan, Ozge Cemiloglu Ulker

{"title":"The investigation of the toxicity of organophosphorus flame retardants (OPFRs) by using in silico toxicity prediction platform ProTox- 3.0.","authors":"Priyanka Banerjee, Onur Ulker, Irem Ozkan, Ozge Cemiloglu Ulker","doi":"10.1080/15376516.2024.2382815","DOIUrl":"10.1080/15376516.2024.2382815","url":null,"abstract":"From the past to the present, many chemicals have been used for the purpose of flame retardant. Due to PBDEs' (Polybrominated diphenyl ether) lipophilic and accumulative properties, some of them are banned from the market. As an alternative to these chemicals, OPFRs (organophosphorus flame retardants) have started to be used as flame retardants. In this article, acute toxicity profiles, mutagenicity, carcinogenicity, blood-brain barrier permeability, ecotoxicity and nutritional toxicity as also AHR, ER affinity and MMP, aromatase affinity, CYP2C9, CYP3A4 interaction of the of 16 different compounds of the OPFRs were investigated using a computational toxicology method; ProTox- 3.0. According to our results, eight compounds were found to be active in terms of carcinogenic effect, whereas two compounds were found to be active for mutagenicity. On the other hand, all compounds were found to be active in terms of blood-barrier permeability. Fourteen compounds and four compounds are found to have ecotoxic and nutritional toxic potency, respectively. Eight compounds were determined as active to AhR, and four chemicals were found to be active in Estrogen Receptor alpha. Eight chemicals were found to be active in terms of mitochondrial membrane potency. Lastly, three chemicals were found to be active in aromatase enzymes. In terms of CYP interaction potencies, eight compounds were found to be active in both CYP2C9 and CYP3A4. This research provided novel insights into the potential toxic effects of OPFRs. However, further studies are needed to evaluate their toxicity. Moreover, these findings lay the groundwork for in vitro and in vivo toxicity research.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"32-42"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141761069","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

Temporal and dosage impact of magnesium oxide nanoparticles on grass carp: unveiling oxidative stress, DNA damage, and antioxidant suppression. 纳米氧化镁颗粒对草鱼的时间和剂量影响：揭示氧化应激、DNA 损伤和抗氧化剂的抑制作用

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2025-01-01 Epub Date: 2024-07-30 DOI: 10.1080/15376516.2024.2382801

Riaz Hussain, Saima Naz, Sana Alam, Hafiz Muhammad Ali, Arooj Ali, Muhammad Shahid Khan, Dalia Fouad, Farid Shokry Ataya, Ayaz Mammadov, Kun Li

{"title":"Temporal and dosage impact of magnesium oxide nanoparticles on grass carp: unveiling oxidative stress, DNA damage, and antioxidant suppression.","authors":"Riaz Hussain, Saima Naz, Sana Alam, Hafiz Muhammad Ali, Arooj Ali, Muhammad Shahid Khan, Dalia Fouad, Farid Shokry Ataya, Ayaz Mammadov, Kun Li","doi":"10.1080/15376516.2024.2382801","DOIUrl":"10.1080/15376516.2024.2382801","url":null,"abstract":"Magnesium oxide nanoparticles (MgO NPs) have gained significant importance in biomedicine and variety of nanotechnology-based materials used in the agriculture and biomedical industries. However, the release of different nanowastes in the water ecosystem becomes a serious concern. Therefore, this study was executed to evaluate the toxic impacts of MgO NPs on grass carp. A total of 60 grass carp were randomly divided in three groups (G0, G1, and G2). Fish reared in group G0 were kept as control while fish of groups G1 and G2 were exposed to 0.5 mg/L and 0.7 mg/L MgO NPs, respectively, mixed in water for 21 days. The 96h median lethal concentration (LC50) of MgO NPs was found to be 4.5 mg/L. Evaluation of oxidative stress biomarkers, antioxidant enzymes, DNA damage in different visceral organs and the presence of micronuclei in erythrocytes were determined on days 7, 14, and 21 of the trial. Results revealed dose- and time-dependent significantly increased values of reactive oxygen species, lipid peroxidation product, DNA damage in multiple visceral organs and formation of micronuclei in the erythrocytes of treated fish (0.7 mg/L). The results on antioxidant profile exhibited significantly lower amounts of total proteins, catalase, superoxide dismutase, and peroxidase in visceral organs of the fish exposed to MgO NPs (0.5 and 0.7 mg/L) at day 21 of trial compared to control group. In conclusion, it has been recorded that MgO NPs severely influence the normal physiological functions of the grass carp even at low doses.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"19-31"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141735062","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

Optimization of long-term incubation of precision-cut kidney slices. 优化精密切割肾切片的长期培养。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2025-01-01 Epub Date: 2024-07-31 DOI: 10.1080/15376516.2024.2382797

C Hoeffner, F Worek, G Horn, N Amend

{"title":"Optimization of long-term incubation of precision-cut kidney slices.","authors":"C Hoeffner, F Worek, G Horn, N Amend","doi":"10.1080/15376516.2024.2382797","DOIUrl":"10.1080/15376516.2024.2382797","url":null,"abstract":"Precision-cut kidney slices (PCKS) provide a powerful model to close the gap between in vivo and in vitro research. Publications by various authors favor different incubation conditions, media, and antibiotics, that have not yet been compared in a standardized manner. After preparation, rat-PCKS were incubated in a total of nine combinations of incubation media and antibiotics for four days. We found that a combination of DMEM/F-12 and gentamicin showed the highest levels of viability. Utilizing both qualitative and quantitative methods, we observed stable levels of cellular viability for 10 days when incubated in the most suitable medium combination of DMEM and gentamicin. Additionally, a calcein acetoxymethyl/ethidium homodimer-1 based live/dead staining, analysis of total protein content and lactate dehydrogenase (LDH) were explored to assess both short- and long-term tissue viability. PCKS showed a significant decrease in total protein content, leveling off at around 60% over the duration of 10 days. To be able to evaluate viability irrespective of decreases in total protein detected, we chose to utilize the alamarBlue Cell Viability Assay. Quantifying both intra- and extracellular activity of LDH, while using different concentrations of ethanol as a positive control, we explored enzyme content as a parameter for cell membrane damage and cytotoxicity in PCKS. Overall, we showed that PCKS are suitable for both short- and long-term observation by optimizing incubation parameters, with numerous possibilities for other assays and methods in future studies.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"11-18"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141735061","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

Undifferentiated versus retinoic acid-differentiated SH-SY5Y cells in investigation of markers of neural function in toxicological research. 在毒理学研究中，未分化与维甲酸-分化的 SH-SY5Y 细胞在神经功能标志物研究中的对比。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2025-01-01 Epub Date: 2024-08-05 DOI: 10.1080/15376516.2024.2385968

Irina Vulin, Dina Tenji, Ivana Teodorovic, Sonja Kaisarevic

{"title":"Undifferentiated versus retinoic acid-differentiated SH-SY5Y cells in investigation of markers of neural function in toxicological research.","authors":"Irina Vulin, Dina Tenji, Ivana Teodorovic, Sonja Kaisarevic","doi":"10.1080/15376516.2024.2385968","DOIUrl":"10.1080/15376516.2024.2385968","url":null,"abstract":"The SH-SY5Y human neuroblastoma cell line is a standard in vitro experimental model of neuronal-like cells used in neuroscience and toxicological research. These cells can be differentiated into mature neurons, most commonly using retinoic acid (RA). Despite differences in characteristics, both undifferentiated and differentiated SH-SY5Y cells are used in research. However, due to uncertainties regarding the expression of specific markers of neural function in each culture, there is no definite conclusion on which culture is better suited for (neuro)toxicological and/or neuroscience investigations. To address this dilemma, we investigated the basal expression/activity of the key elements of acetylcholine, dopamine, serotonin, and GABA neurotransmitter pathways, along with the elements involved in exocytosis of neurotransmitters, and neuron electrophysiological activity in undifferentiated and in RA-differentiated SH-SY5Y cells using a six-day differentiation protocol. Our findings revealed that both SH-SY5Y cell types are functionally active. While undifferentiated SH-SY5Y cells exhibited greater multipotency in the expression of tested markers, most of those markers expressed in both cell types showed higher expression levels in RA-differentiated SH-SY5Y cells. Our results suggest that the six-day differentiation protocol with RA induces maturation, but not differentiation of the cells into specific neuron phenotype. The greater multipotency of undifferentiated cells in neural markers expression, together with their higher sensitivity to xenobiotic exposure and more simple cultivation protocols, make them a better candidate for high throughput toxicological screenings. Differentiated neurons are better suited for neuroscience researches that require higher expression of more specific neural markers and the specific types of neural cells.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"53-63"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141793561","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

Fifteen day repeat air: liquid Interface air-only exposures can cause respiratory epithelium injury in MucilAir^™ nasal respiratory epithelial cells that parallels chemically induced cytotoxicity. 在 MucilAir™ 鼻呼吸道上皮细胞中，15 天重复接触空气：仅接触液体界面空气会造成呼吸道上皮细胞损伤，这种损伤与化学诱导的细胞毒性相似。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2025-01-01 Epub Date: 2024-07-30 DOI: 10.1080/15376516.2024.2382794

Leslie Recio, Raymond Samuel, Susan A Elmore, Jamie Scaglione

{"title":"Fifteen day repeat air: liquid Interface air-only exposures can cause respiratory epithelium injury in MucilAir™ nasal respiratory epithelial cells that parallels chemically induced cytotoxicity.","authors":"Leslie Recio, Raymond Samuel, Susan A Elmore, Jamie Scaglione","doi":"10.1080/15376516.2024.2382794","DOIUrl":"10.1080/15376516.2024.2382794","url":null,"abstract":"New Approach Methodologies (NAMs) are being widely used to reduce, refine, and replace, animal use in studying toxicology. For respiratory toxicology, this includes in silico and in vitro alternatives using air:liquid interface (ALI) exposures to replace traditional in vivo inhalation studies. In previous studies using 1,3-dichloropropene (1,3-DCP), a 5-day 4 h repeat exposures of MucilAir™ nasal cell culture models caused, dose-dependent cytotoxicity, depletion of GSH, changes in differential gene expression and histopathological transitions in cellular morphology from pseudostratified columnar epithelium to squamous epithelium. In this report we attempted to extend these studies using 15-day 1,3-DCP 4 h exposures to using MucilAir™ nasal cultures as outlined by an US EPA recent task order (US EPA 2023). For the 15-day repeat exposure, there were severe histopathologic changes in the MucilAir™ nasal mock-treatment (air-only) VITROCELL® chamber controls compared to incubator controls preventing any further analysis. The histopathological transitions in cellular morphology from pseudostratified columnar epithelium to squamous epithelium observed in the air only control in this study and previously with 1,3-DCP in MucilAir™ nasal cultures is also a hallmark of chemically induced cytotoxic responses in vivo in the respiratory tract. Histopathology assessments of 3D respiratory tract models used in ALI exposures can provide the linkage between in vitro to in vivo outcomes as part of the validation efforts of ALI use in regulatory toxicology. This report indicates that importance of histopathological assessments of incubator and mock-treatment (air-only) controls from each ALI exposure experiment along with exposed cell based model.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"81-87"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141793560","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 investigation the effects of iodinated contrast media on endothelial cell viability, cell cycle, and apoptosis. 体外研究含碘造影剂对内皮细胞活力、细胞周期和凋亡的影响。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2025-01-01 Epub Date: 2024-07-31 DOI: 10.1080/15376516.2024.2386605

Gunjanaporn Tochaikul, Krai Daowtak, Chalermchai Pilapong, Nutthapong Moonkum

{"title":"In vitro investigation the effects of iodinated contrast media on endothelial cell viability, cell cycle, and apoptosis.","authors":"Gunjanaporn Tochaikul, Krai Daowtak, Chalermchai Pilapong, Nutthapong Moonkum","doi":"10.1080/15376516.2024.2386605","DOIUrl":"10.1080/15376516.2024.2386605","url":null,"abstract":"In medical practice, iodine contrast media are necessary for diagnostic techniques. However, it comes with a potential risk to the patient in the form of allergic reactions. The aim of this research is to study the effects of iodine contrast media on endothelial cells in an in vitro system at various concentrations, specifically investigating their impact on cell viability, cell cycle, and apoptosis in the treated cells within the field of diagnostic radiology. Our results showed that in iodine contrast media, when the concentration was within the range of 2.5-50 mgI/ml, cell viability decreased by 50%. Conversely, exposure to ioversol at concentrations between 12.5 and 50.0 mgI/ml resulted in a notable increase in the percentage of total apoptotic cells, including both early and late apoptosis. In conclusion, our in vitro investigation sheds light on the effect of iodinated contrast media on endothelial cell viability, cell cycle progression, and apoptosis. These findings contribute valuable insights to ensure the safety of their use, aligning with guidelines in radiological procedures. Further research and adherence to established guidelines are crucial for refining our understanding and promoting the safe application of iodinated contrast media in the field of radiology.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"64-71"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141856564","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

Using machine learning to classify the immunosuppressive activity of per- and polyfluoroalkyl substances. 利用机器学习对全氟化烷基和多氟化烷基物质的免疫抑制活性进行分类。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2025-01-01 Epub Date: 2024-08-05 DOI: 10.1080/15376516.2024.2387733

Yuxin Xuan, Yulu Wang, Rui Li, Yuyan Zhong, Na Wang, Lingyin Zhang, Qian Chen, Shuling Yu, Jintao Yuan

{"title":"Using machine learning to classify the immunosuppressive activity of per- and polyfluoroalkyl substances.","authors":"Yuxin Xuan, Yulu Wang, Rui Li, Yuyan Zhong, Na Wang, Lingyin Zhang, Qian Chen, Shuling Yu, Jintao Yuan","doi":"10.1080/15376516.2024.2387733","DOIUrl":"10.1080/15376516.2024.2387733","url":null,"abstract":"Per- and polyfluoroalkyl substances (PFASs), one of the persistent organic pollutants, have immunosuppressive effects. The evaluation of this effect has been the focus of regulatory toxicology. In this investigation, 146 PFASs (immunosuppressive or nonimmunosuppressive) and corresponding concentration gradients were collected from literature, and their structures were characterized by using Dragon descriptors. Feature importance analysis and stepwise feature elimination are used for feature selection. Three machine learning (ML) methods, namely Random Forest (RF), Extreme Gradient Boosting Machine (XGB), and Categorical Boosting Machine (CB), were utilized for model development. The model interpretability was explored by feature importance analysis and correlation analysis. The findings indicated that the three models developed have exhibited excellent performance. Among them, the best-performing RF model has an average AUC score of 0.9720 for the testing set. The results of the feature importance analysis demonstrated that concentration, SpPosA_X, IVDE, R2s, and SIC2 were the crucial molecular features. Applicability domain analysis was also performed to determine reliable prediction boundaries for the model. In conclusion, this study is the first application of ML models to investigate the immunosuppressive activity of PFASs. The variables used in the models can help understand the mechanism of the immunosuppressive activity of PFASs, allow researchers to more effectively assess the immunosuppressive potential of a large number of PFASs, and thus better guide environmental and health risk assessment efforts.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"72-80"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141894332","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

Inonotus obliquus aqueous extract inhibits intestinal inflammation and insulin metabolism defects in Drosophila. 乌骨鸡水提取物可抑制果蝇肠道炎症和胰岛素代谢缺陷。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2024-11-01 Epub Date: 2024-06-27 DOI: 10.1080/15376516.2024.2368795

Shichao Yu, Zhixian Lai, Hongmei Xue, Jiahua Zhu, Guanhua Yue, Jiewei Wang, Li Hua Jin

{"title":"Inonotus obliquus aqueous extract inhibits intestinal inflammation and insulin metabolism defects in Drosophila.","authors":"Shichao Yu, Zhixian Lai, Hongmei Xue, Jiahua Zhu, Guanhua Yue, Jiewei Wang, Li Hua Jin","doi":"10.1080/15376516.2024.2368795","DOIUrl":"10.1080/15376516.2024.2368795","url":null,"abstract":"In biomedical research, the fruit fly (Drosophila melanogaster) is among the most effective and flexible model organisms. Through the use of the Drosophila model, molecular mechanisms of human diseases can be investigated and candidate pharmaceuticals can be screened. White rot fungus Inonotus obliquus is a member of the family Hymenochaetaceae. Due to its multifaceted pharmacological effects, this fungus has been the subject of scientific investigation. Nevertheless, the precise mechanisms by which Inonotus obliquus treats diseases remain unclear. In this study, we prepared an aqueous extract derived from Inonotus obliquus and demonstrated that it effectively prevented the negative impacts of inflammatory agents on flies, including overproliferation and overdifferentiation of intestinal progenitor cells and decreased survival rate. Furthermore, elevated reactive oxygen species levels and cell death were alleviated by Inonotus obliquus aqueous extract, suggesting that this extract inhibited intestinal inflammation. Additionally, Inonotus obliquus aqueous extract had an impact on the insulin pathway, as it alleviated growth defects in flies that were fed a high-sugar diet and in chico mutants. In addition, we determined the composition of Inonotus obliquus aqueous extract and conducted a network pharmacology analysis in order to identify prospective key compounds and targets. In brief, Inonotus obliquus aqueous extract exhibited considerable potential as a therapeutic intervention for human diseases. Our research has established a foundational framework that supports the potential clinical implementation of Inonotus obliquus.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"970-984"},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141318366","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

Spatial memory impairment is associated with decreased dopamine-β-hydroxylase activity in the brains of rats exposed to manganese chloride. 暴露于氯化锰的大鼠大脑中的空间记忆障碍与多巴胺-β-羟化酶活性降低有关。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2024-11-01 Epub Date: 2024-07-17 DOI: 10.1080/15376516.2024.2379012

Valentina Mikhailovna Kudrinskaya, Andrey Pavlovich Ivlev, Daria Alexeevna Obukhova, Viktoriya Aleksandrovna Maystrenko, Tatiana Valentinovna Tiutiunnik, Dmitrii Sergeevich Traktirov, Marina Nikolaevna Karpenko, Irina Sergeevna Ivleva

{"title":"Spatial memory impairment is associated with decreased dopamine-β-hydroxylase activity in the brains of rats exposed to manganese chloride.","authors":"Valentina Mikhailovna Kudrinskaya, Andrey Pavlovich Ivlev, Daria Alexeevna Obukhova, Viktoriya Aleksandrovna Maystrenko, Tatiana Valentinovna Tiutiunnik, Dmitrii Sergeevich Traktirov, Marina Nikolaevna Karpenko, Irina Sergeevna Ivleva","doi":"10.1080/15376516.2024.2379012","DOIUrl":"10.1080/15376516.2024.2379012","url":null,"abstract":"Chronic exposure to manganese compounds leads to accumulation of the manganese in the basal ganglia and hippocampus. High levels of manganese in these structures lead to oxidative stress, neuroinflammation, imbalance of brain neurotransmitters, and hyperactivation of calpains mediating neurotoxicity and causing motor and cognitive impairment. The purpose of this work was to study the effect of excess manganese chloride intake on rats' spatial memory and on dopamine-β-hydroxylase (DβH) activity under conditions of calpain activity suppression. Rats were divided into 3 groups of 10 animals each. Group 1 received MnCl2 (30 days, 5 mg/kg/day, intranasally), group 2 received MnCl2 (30 days, 5 mg/kg/day, intranasally) and calpain inhibitor Cast (184-210) (30 days, 5 µg/kg/day, intranasally), and group 3 received sterile saline (30 days in a volume of 20 μl, intranasally). The spatial working memory was assessed using Morris water maze test. DβH activity was determined by HPLC. We have shown that in response to excessive intake of MnCl2, there was a development of cognitive impairments in rats, which was accompanied by a decrease in DβH activity in the hippocampus. The severity of cognitive impairment was reduced by inhibiting the activity of m-calpain. The protective effect of calpain inhibitors was achieved not through an effect on DβH activity. Thus, the development of therapeutic regimens for the treatment of manganism using dopaminomimetics and/or by inhibiting calpains, must be performed taking into account the manganese-induced decrease of DβH activity and the inability to influence this process with calpain inhibitors.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1035-1044"},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141634623","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

Naturally-derived phenethyl isothiocyanate modulates apoptotic induction through regulation of the intrinsic cascade and resulting apoptosome formation in human malignant melanoma cells. 天然萃取的异硫氰酸苯乙酯通过调节人恶性黑色素瘤细胞的内在级联和凋亡小体的形成来调节凋亡诱导。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2024-11-01 Epub Date: 2024-06-25 DOI: 10.1080/15376516.2024.2369666

Venetia Tragkola, Ioannis Anestopoulos, Sotiris Kyriakou, Tom Amery, Rodrigo Franco, Aglaia Pappa, Mihalis I Panayiotidis

{"title":"Naturally-derived phenethyl isothiocyanate modulates apoptotic induction through regulation of the intrinsic cascade and resulting apoptosome formation in human malignant melanoma cells.","authors":"Venetia Tragkola, Ioannis Anestopoulos, Sotiris Kyriakou, Tom Amery, Rodrigo Franco, Aglaia Pappa, Mihalis I Panayiotidis","doi":"10.1080/15376516.2024.2369666","DOIUrl":"10.1080/15376516.2024.2369666","url":null,"abstract":"Malignant melanoma is the most aggressive type of skin cancer with increasing incidence rates worldwide. On the other hand, watercress is a rich source of phenethyl isothiocyanate (PEITC), among others, which has been widely investigated for its anticancer properties against various cancers. In the present study, we evaluated the role of a watercress extract in modulating apoptotic induction in an in vitro model of human malignant melanoma consisting of melanoma (A375, COLO-679, COLO-800), non-melanoma epidermoid carcinoma (A431) and immortalized, non-tumorigenic keratinocyte (HaCaT) cells. Moreover, the chemical composition of the watercress extract was characterized through UPLC MS/MS and other analytical methodologies. In addition, cytotoxicity was assessed by the alamar blue assay whereas apoptosis was determined, initially, by a multiplex activity assay kit (measuring levels of activated caspases -3, -8 and -9) as well as by qRT-PCR for the identification of major genes regulating apoptosis. In addition, protein expression levels were evaluated by western immunoblotting. Our data indicate that the extract contains various phytochemicals (e.g. phenolics, flavonoids, pigments, etc.) while isothiocyanates (ITCs; especially PEITC) were the most abundant. In addition, the extract was shown to exert a significant time- and dose-dependent cytotoxicity against all malignant melanoma cell lines while non-melanoma and non-tumorigenic cells exhibited significant resistance. Finally, expression profiling revealed a number of genes (and corresponding proteins) being implicated in regulating apoptotic induction through activation of the intrinsic apoptotic cascade. Overall, our data indicate the potential of PEITC as a promising anti-cancer agent in the clinical management of human malignant melanoma.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"985-999"},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141451546","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