Toxicology Mechanisms and Methods最新文献

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Toxicological impact of copper nanoparticles on rainbow trout: hematological, biochemical, antioxidant, and histopathological responses with oxidative gene expression. 纳米铜颗粒对虹鳟鱼的毒理学影响:血液学、生物化学、抗氧化和组织病理学反应以及氧化基因表达。
IF 3.2 4区 医学
Toxicology Mechanisms and Methods Pub Date : 2024-12-09 DOI: 10.1080/15376516.2024.2438120
Saba Khursheed Khan, Joydeep Dutta, Mohd Ashraf Rather, Ishtiyaq Ahmad, Junaid Nazir, Arun Karnwal
{"title":"Toxicological impact of copper nanoparticles on rainbow trout: hematological, biochemical, antioxidant, and histopathological responses with oxidative gene expression.","authors":"Saba Khursheed Khan, Joydeep Dutta, Mohd Ashraf Rather, Ishtiyaq Ahmad, Junaid Nazir, Arun Karnwal","doi":"10.1080/15376516.2024.2438120","DOIUrl":"https://doi.org/10.1080/15376516.2024.2438120","url":null,"abstract":"<p><p>Copper nanoparticles (CuNPs) are increasingly used across various industries due to their catalytic, antimicrobial, and electrical properties. However, their potential toxicity in aquatic environments, particularly to non-target organisms like fish, remains poorly understood. This study investigated the effects of CuNP exposure on rainbow trout (<i>Oncorhynchus mykiss</i>) by comprehensively evaluating hematological, biochemical, antioxidant, molecular, and histopathological parameters. Rainbow trout fingerlings were exposed to varying concentrations of CuNPs (0.2 mg/L, 0.6 mg/L, and 1.0 mg/L) for 7, 14, and 21 days. The results revealed significant dose-dependent declines in hemoglobin (Hb) and red blood cell (RBC) counts, alongside increases in white blood cell (WBC) counts, indicating an immune response to CuNPs-induced stress. Serum biochemistry showed disruptions in albumin, globulin, cholesterol, and triglycerides, suggesting impaired liver function and altered lipid metabolism. Antioxidant enzyme activity, including catalase (CAT), increased significantly, reflecting oxidative stress, while lipid peroxidation (LPO) levels unexpectedly decreased, suggesting possible activation of compensatory mechanisms. Histopathological analysis confirmed severe gill and liver damage, including hypertrophy, hyperplasia, lamellar fusion, necrosis, and cellular degeneration. Molecular analysis showed upregulation of oxidative and, inflammatory genes, and signs of apoptosis. These findings underscore the toxic potential of CuNPs in aquatic environments and highlight the need for careful regulation and environmental monitoring to mitigate their impact.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-16"},"PeriodicalIF":3.2,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802176","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
Thirty-day oral exposure to acetamiprid induces biochemical and histological alterations in rat pancreas: protective effects of carnosine supplementation. 口服乙酰氨脒30天可诱导大鼠胰腺生化和组织学改变:肌肽补充的保护作用。
IF 3.2 4区 医学
Toxicology Mechanisms and Methods Pub Date : 2024-12-03 DOI: 10.1080/15376516.2024.2435350
Imen Benchikh, Kaddour Ziani, Abdelkrim Benalia, Ahmed Abdelhammid Djebbar, Hayat Argoub, Méghit Boumediène Khaled
{"title":"Thirty-day oral exposure to acetamiprid induces biochemical and histological alterations in rat pancreas: protective effects of carnosine supplementation.","authors":"Imen Benchikh, Kaddour Ziani, Abdelkrim Benalia, Ahmed Abdelhammid Djebbar, Hayat Argoub, Méghit Boumediène Khaled","doi":"10.1080/15376516.2024.2435350","DOIUrl":"https://doi.org/10.1080/15376516.2024.2435350","url":null,"abstract":"<p><p>Acetamiprid is a neonicotinoid insecticide used against various insect pests. Serious concerns are emerging regarding their adverse effects on non-target organisms and organs. This study aimed to investigate the mechanistic toxic effect of oral administration of acetamiprid at 21.7 and 43.4 mg/kg body weight on the histological structure and pancreatic function of male Wistar rats and the potential effect of carnosine in mitigating this toxicity for 30 consecutive days. Thirty-six animals were divided into six groups: the control group received distilled water, the second group received 200 mg/kg body weight of carnosine, two groups received 21.7 and 43.4 mg/kg of acetamiprid, and two groups received 21.7 and 43.4 mg/kg + 200 kg/kg body weight of acetamiprid and carnosine, respectively. Acetamiprid caused a significant decrease in body weight (<i>p</i> < 0.001), pancreatic somatic index (<i>p</i> < 0.001), and amylase level (<i>p</i> ≤ 0.0001) and increased lipase level (<i>p</i> ≤ 0.0001), blood glucose level (<i>p</i> ≤ 0.0001), histological scores (<i>p</i> ≤ 0.01), and malondialdehyde level (0.01<<i>p</i> < 0.0001). Administration of carnosine led to a slight improvement in the increase of lipase (<i>p</i> ≤ 0.01) and the decrease of amylase (<i>p</i> ≤ 0.001) secretions and prevention of histopathological features induced by acetamiprid. Our results pointed out for the first time the toxic effect of acetamiprid and the preventive effect of carnosine on rat pancreatic structure and function.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-11"},"PeriodicalIF":3.2,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772594","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
Human stromal cell-based protocol to generate astrocytes: a straightforward in vitro predictive strategy in neurotoxicology. 基于人类基质细胞生成星形胶质细胞的方案:神经毒理学中一种直接的体外预测策略。
IF 3.2 4区 医学
Toxicology Mechanisms and Methods Pub Date : 2024-12-03 DOI: 10.1080/15376516.2024.2435351
Uliana De Simone, Francesca Caloni, Patrizia Pignatti, Carlo Gaetano, Carlo Alessandro Locatelli, Teresa Coccini
{"title":"Human stromal cell-based protocol to generate astrocytes: a straightforward <i>in vitro</i> predictive strategy in neurotoxicology.","authors":"Uliana De Simone, Francesca Caloni, Patrizia Pignatti, Carlo Gaetano, Carlo Alessandro Locatelli, Teresa Coccini","doi":"10.1080/15376516.2024.2435351","DOIUrl":"https://doi.org/10.1080/15376516.2024.2435351","url":null,"abstract":"<p><p>The inherent adaptability of human mesenchymal stromal cells (hMSCs) to differentiate into neural lineages provides a valuable resource for investigating potential neurotoxicity in humans. By harnessing the ability of hMSCs to transform into astrocytes, we can evaluate the effects of various agents on these vital cells. Our protocol employs hMSCs sourced from umbilical cord tissue, ensuring a readily available supply of high-quality cells. The hMSC-to-neural workflow encompasses six essential steps: hMSC culture, followed by the generation of embryoid bodies (EBs) from these cells on specialized surfaces. Next, EBs and cells are expanded in a growth-promoting medium, directing them toward neural lineages. Subsequent differentiation into immature astrocytes is achieved through the use of specific factors. The process continues with the maturation of EBs/cells into astrocyte-like cells (hALCs) under optimized conditions, culminating in the final development of hALCs in a specialized medium. This methodology yields cells that display astrocyte morphology and express characteristic markers such as GFAP and S100β. The protocol is efficient, requiring roughly 6 weeks to generate hALCs from primary hMSCs without genetic manipulation. The application of hMSCs in evaluating cell damage triggered by neurotoxicants like MeHg and MGO underscores their potential as a valuable component within a more extensive battery of neurotoxicity tests.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-16"},"PeriodicalIF":3.2,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772653","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":"<i>Inonotus obliquus</i> aqueous extract inhibits intestinal inflammation and insulin metabolism defects in <i>Drosophila</i>.","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":"<p><p>In biomedical research, the fruit fly (<i>Drosophila melanogaster</i>) is among the most effective and flexible model organisms. Through the use of the <i>Drosophila</i> model, molecular mechanisms of human diseases can be investigated and candidate pharmaceuticals can be screened. White rot fungus <i>Inonotus obliquus</i> is a member of the family <i>Hymenochaetaceae</i>. Due to its multifaceted pharmacological effects, this fungus has been the subject of scientific investigation. Nevertheless, the precise mechanisms by which <i>Inonotus obliquus</i> treats diseases remain unclear. In this study, we prepared an aqueous extract derived from <i>Inonotus obliquus</i> 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 <i>Inonotus obliquus</i> aqueous extract, suggesting that this extract inhibited intestinal inflammation. Additionally, <i>Inonotus obliquus</i> 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 <i>chico</i> mutants. In addition, we determined the composition of <i>Inonotus obliquus</i> aqueous extract and conducted a network pharmacology analysis in order to identify prospective key compounds and targets. In brief, <i>Inonotus obliquus</i> 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 <i>Inonotus obliquus</i>.</p>","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":"<p><p>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 MnCl<sub>2</sub> (30 days, 5 mg/kg/day, intranasally), group 2 received MnCl<sub>2</sub> (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 MnCl<sub>2</sub>, 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.</p>","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":"<p><p>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 <i>in vitro</i> 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.</p>","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
Hesperetin protects against rotenone-induced motor disability and neurotoxicity via the regulation of SIRT1/NLRP3 signaling. 橙皮素通过调节SIRT1/NLRP3信号传导,防止鱼藤酮诱发的运动障碍和神经毒性。
IF 3.2 4区 医学
Toxicology Mechanisms and Methods Pub Date : 2024-11-01 Epub Date: 2024-08-14 DOI: 10.1080/15376516.2024.2390646
Hayam Ateyya, Huda M Atif, Noha M Abd El-Fadeal, Eman Abul-Ela, Rania I Nadeem, Nermin I Rizk, Fatma Alzahraa M Gomaa, Sozan M Abdelkhalig, Afaf A Aldahish, Manal S Fawzy, Bassant M Barakat, Sawsan A Zaitone
{"title":"Hesperetin protects against rotenone-induced motor disability and neurotoxicity via the regulation of SIRT1/NLRP3 signaling.","authors":"Hayam Ateyya, Huda M Atif, Noha M Abd El-Fadeal, Eman Abul-Ela, Rania I Nadeem, Nermin I Rizk, Fatma Alzahraa M Gomaa, Sozan M Abdelkhalig, Afaf A Aldahish, Manal S Fawzy, Bassant M Barakat, Sawsan A Zaitone","doi":"10.1080/15376516.2024.2390646","DOIUrl":"10.1080/15376516.2024.2390646","url":null,"abstract":"<p><p>Rotenone is a pesticide that causes complex I inhibition and is widely known to induce motor disability and experimental Parkinson's disease (PD) in rodents. Evidence suggests a crucial role for sirtuin/nuclear factor-kappaB/nod-like receptor family, pyrin domain-containing 3 (SIRT1/NFκB/NLRP3) signaling and inflammation in PD and rotenone neurotoxicity. Hesperetin (C16H14O6) is a citrus flavonoid with documented anti-inflammatory activity. We investigated the value of hesperetin in delaying rotenone-induced PD in mice and the possible modulation of inflammatory burden. PD was induced in mice <i>via</i> rotenone injections. Groups were assigned as a vehicle, PD, or PD + hesperetin (50 or 100 mg/kg) and compared for the motor function, protein level (by ELISA), and gene expression (by real-time PCR) of the target proteins, histopathology, and immunohistochemistry for tyrosine hydroxylase enzyme. Hesperetin (50 or 100 mg/kg) alleviated the motor disability and the striatal dopamine level and decreased the expression of <i>NLRP3</i> and <i>NF-κB</i> but increased <i>SIRT1</i> expression (<i>p</i> < 0.05). Further, it enhanced the neural viability and significantly decreased neural degeneration in the substantia nigra, hippocampus, and cerebral cortex (<i>p</i> < 0.05). Taken together, we propose that hesperetin mediates its neuroprotective function <i>via</i> alleviating modulation of the SIRT1/NFκB/NLRP3 pathway. Therefore, hesperetin might delay the PD progression.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1045-1060"},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907721","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
Metformin attenuates PM2.5-induced oxidative stress by inhibiting the AhR/CYP1A1 pathway in proximal renal tubular epithelial cells. 二甲双胍通过抑制近端肾小管上皮细胞中的AhR/CYP1A1通路减轻PM2.5诱导的氧化应激。
IF 3.2 4区 医学
Toxicology Mechanisms and Methods Pub Date : 2024-11-01 Epub Date: 2024-07-22 DOI: 10.1080/15376516.2024.2378296
Jing Cui, Weilin Chen, Dongdong Zhang, Mengqiu Lu, Zhijun Huang, Bin Yi
{"title":"Metformin attenuates PM<sub>2.5</sub>-induced oxidative stress by inhibiting the AhR/CYP1A1 pathway in proximal renal tubular epithelial cells.","authors":"Jing Cui, Weilin Chen, Dongdong Zhang, Mengqiu Lu, Zhijun Huang, Bin Yi","doi":"10.1080/15376516.2024.2378296","DOIUrl":"10.1080/15376516.2024.2378296","url":null,"abstract":"<p><p>The harmful effects of PM<sub>2.5</sub> on human health, including an increased risk of chronic kidney disease (CKD), have raised a lot of attention, but the underlying mechanisms are unclear. We used the Shanghai Meteorological and Environmental Animal Exposure System (Shanghai-METAS) to simulate the inhalation of PM<sub>2.5</sub> in the real environment and established an animal model by exposing C57BL/6 mice to filtered air (FA) and Particulate Matter (PM<sub>2.5</sub>) for 8 weeks. PM<sub>2.5</sub> impaired the renal function of the mice, and the renal tubules underwent destructive changes. Analysis of NHANES data showed a correlation between reduced kidney function and higher blood levels of PM<sub>2.5</sub> components, polychlorinated biphenyls (PCBs) and dioxins, which are Aryl hydrocarbon Receptor (AhR) ligands. PM<sub>2.5</sub> exposure induced higher levels of AhR and CYP1A1 and oxidative stress as evidenced by the higher levels of ROS, MDA, and GSSG in kidneys of mice. PM<sub>2.5</sub> exposure led to AhR overexpression and nuclear translocation in proximal renal tubular epithelial cells. Inhibition of AhR reduced CYP1A1 expression and PM<sub>2.5</sub>-increased levels of ROS, MDA and GSSG. Our study suggested metformin can mitigate PM<sub>2.5</sub>-induced oxidative stress by inhibiting the AhR/CYP1A1 pathway. These findings illuminated the role of AhR/CYP1A1 pathway in PM<sub>2.5</sub>-induced kidney injury and the protective effect of metformin on PM<sub>2.5</sub>-induced cellular damage, offering new insights for air pollution-related renal diseases.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1022-1034"},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141735060","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
Assessment of genotoxic damage induced by exposure to binary mixtures of polycyclic aromatic hydrocarbons and three heavy metals in male mice. 评估雄性小鼠暴露于多环芳烃和三种重金属的二元混合物诱发的基因毒性损伤。
IF 3.2 4区 医学
Toxicology Mechanisms and Methods Pub Date : 2024-11-01 Epub Date: 2024-06-11 DOI: 10.1080/15376516.2024.2365434
Norberto Alarcón-Herrera, Sandra Gómez-Arroyo, Saúl Flores-Maya, Ana Rosa Flores-Márquez, Paulina Abrica-González
{"title":"Assessment of genotoxic damage induced by exposure to binary mixtures of polycyclic aromatic hydrocarbons and three heavy metals in male mice.","authors":"Norberto Alarcón-Herrera, Sandra Gómez-Arroyo, Saúl Flores-Maya, Ana Rosa Flores-Márquez, Paulina Abrica-González","doi":"10.1080/15376516.2024.2365434","DOIUrl":"10.1080/15376516.2024.2365434","url":null,"abstract":"<p><strong>Introduction: </strong>Heavy metals (HM) and polycyclic aromatic hydrocarbons (PAHs) exposition has been associated with health problems. Therefore, this research evaluated genotoxicity induced in male mice strain CD-1 exposed to benzo[a]anthracene (B[a]A) and benzo[a]pyrene (B[a]P) and their interaction with Fe, Pb, and Al.</p><p><strong>Methods: </strong>Groups of animals were exposed intraperitoneally to HM, PAHs, and mixtures of both. Peripheral blood samples were taken from 0 to 96 h at 24 h intervals; genotoxicity was determined by micronucleus tests and comet assay. Additionally, toxicity and viability were evaluated.</p><p><strong>Results: </strong>HM and PAHs individually were genotoxic. About toxicity, only Al altered polychromatic erythrocytes number and did not change leukocytes viability. Concerning mixtures, Fe + B[a]P, Fe + B[a]A, Pb + B[a]P increased genotoxicity. There were no changes with Pb + B[a]A. Finally, Al mixtures with both PAHs damage was decreased.</p><p><strong>Conclusions: </strong>Exposure to HM and PAH caused genetic damage. Fe, Al, and B[a]A, established a genotoxic potential. Every metal can interact with PAHs in different ways. Also, the micronucleus test and the comet assay demonstrated their high capacity and reliability to determine the genotoxic potential of the compounds evaluated in this work.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"955-969"},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306933","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 evaluation of the toxicological effects of cooking oil fumes using a self-designed microfluidic chip. 利用自行设计的微流控芯片对食用油油烟的毒理效应进行体外评估。
IF 3.2 4区 医学
Toxicology Mechanisms and Methods Pub Date : 2024-11-01 Epub Date: 2024-06-30 DOI: 10.1080/15376516.2024.2369941
Boyang Feng, Xiang Li, Zezhi Li, Junwei Zhao, Kejian Liu, Fuwei Xie, Xiaobing Zhang
{"title":"<i>In vitro</i> evaluation of the toxicological effects of cooking oil fumes using a self-designed microfluidic chip.","authors":"Boyang Feng, Xiang Li, Zezhi Li, Junwei Zhao, Kejian Liu, Fuwei Xie, Xiaobing Zhang","doi":"10.1080/15376516.2024.2369941","DOIUrl":"10.1080/15376516.2024.2369941","url":null,"abstract":"<p><p>Cooking oil fumes (COFs) are widely acknowledged as substantial contributors to indoor air pollution, having detrimental effects on human health. Despite the existence of commercialized <i>in vitro</i> aerosol exposure platforms, assessment risks of aerosol pollutants are primarily evaluated based on multiwell plate experiments by trapping and redissolving aerosols to conduct comprehensive <i>in vitro</i> immersion exposure manner. Therefore, an innovative real-time exposure system for COF aerosol was constructed, featuring a self-designed microfluidic chip as its focal component. The chip was used to assess toxicological effects of <i>in vitro</i> exposure to COF aerosol on cells cultured at the gas-liquid interface. Meanwhile, we used transcriptomics to analyze genes that exhibited differential expression in cells induced by COF aerosol. The findings indicated that the MAPK signaling pathway, known for its involvement in inflammatory response and oxidative stress, played a crucial role in the biological effects induced by COF aerosol. Biomarkers associated with inflammatory response and oxidative stress exhibited corresponding alterations. Furthermore, the concentration of COF aerosol exposure and post-exposure duration exert decisive effects on these biomarkers. Thus, the study suggests that COF can induce oxidative stress and inflammatory response in BEAS-2B cells, potentially exerting a discernible impact on human health.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1000-1009"},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421018","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
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