Toxicology Research最新文献_第6页

Liquid chromatography-high-resolution mass spectrometry-based metabolomics revealing the effects of zearalenone and alpha-zearalenol on human endometrial cancer cells. 基于液相色谱-高分辨质谱的代谢组学揭示玉米赤霉烯酮和α-玉米赤霉烯醇对人类子宫内膜癌细胞的影响

IF 2.2 4区医学

Toxicology Research Pub Date : 2024-10-15 eCollection Date: 2024-10-01 DOI: 10.1093/toxres/tfae169

Marhaba Marhaba, Narendra Kumar Nagendla, Saria Anjum, Sireesha Ganneru, Varsha Singh, Saurabh Pal, Mohana Krishna Reddy Mudiam, Kausar Mahmood Ansari

{"title":"Liquid chromatography-high-resolution mass spectrometry-based metabolomics revealing the effects of zearalenone and alpha-zearalenol on human endometrial cancer cells.","authors":"Marhaba Marhaba, Narendra Kumar Nagendla, Saria Anjum, Sireesha Ganneru, Varsha Singh, Saurabh Pal, Mohana Krishna Reddy Mudiam, Kausar Mahmood Ansari","doi":"10.1093/toxres/tfae169","DOIUrl":"https://doi.org/10.1093/toxres/tfae169","url":null,"abstract":"Human exposure to mycotoxins through food involve a mixture of compounds, which can be harmful to human health. The Fusarium fungal species are known to produce zearalenone (ZEN), a non-steroidal estrogenic mycotoxin, and its metabolite alpha-zearalenol (α-ZEL), both of which possess endocrine-disruptive properties. Given their potential harm to human health through food exposure, investigating the combined effects of ZEN and α-ZEL becomes crucial. Hence, the combined impact of ZEN and α-ZEL study hold significant importance. This in vitro study delves into the critical area, examining their combined impact on the proliferation and metabolic profile of endometrial cancer Ishikawa cells via sulforhodamine, clonogenic, proliferating cell nuclear antigen (PCNA) and liquid chromatography-high resolution mass spectrometry (LC-HRMS) based untargeted metabolomics. Low concentrations of ZEN (25 nm), α-ZEL (10 nm), or a combination of both were observed to significantly enhance cell proliferation of Ishikawa cells, as evidenced by PCNA immunostaining, immunoblotting as well and clonogenic assays. The metabolomics revealed the perturbations in glycerophospholipid metabolism, nicotinate and nicotinamide metabolism and phenylalanine, tyrosine, tryptophan biosynthesis provides valuable insights into potential mechanism by which these mycotoxins may facilitate cell proliferation. However, further investigations are warranted to comprehensively understand the implications of these findings and their possible implications for human health.","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 5","pages":"tfae169"},"PeriodicalIF":2.2,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11474235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453741","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}

引用次数: 0

Liver toxicity and repair evaluated by histopathology and electric modulus. 通过组织病理学和电模量评估肝脏毒性和修复。

IF 2.2 4区医学

Toxicology Research Pub Date : 2024-10-15 eCollection Date: 2024-10-01 DOI: 10.1093/toxres/tfae175

Azhar M Elwan, Ibrahim M Farag, Mohamed M M Elnasharty

{"title":"Liver toxicity and repair evaluated by histopathology and electric modulus.","authors":"Azhar M Elwan, Ibrahim M Farag, Mohamed M M Elnasharty","doi":"10.1093/toxres/tfae175","DOIUrl":"https://doi.org/10.1093/toxres/tfae175","url":null,"abstract":"Detoxification is one of the most important liver functions. Therefore, liver is the front line of defense when the biosystem faces drug overdose, toxins, and anything that may cause harm. Some famous antibiotics are known for their side effects on liver; one of them is amoxicillin, AM. This work has investigated the toxic effect of amoxicillin on rat's liver with overdose (90 mg/kg) and has studied the ameliorative role of protective and therapeutic Ashwagandha seeds extract (ASE) at doses (100, 200, and 300 mg/kg) against this toxicity. To achieve this work, the authors used two modalities; the first is liver histopathology to figure out the amoxicillin and ASE effects and to detect the sensitivity of another modality; the electric modulus, and its related thermodynamic parameters of liver tissue. Histopathological examination showed that the role of therapeutic ASE in reducing amoxicillin (AM) toxicity was more effective than the protective one. Also, most dielectric and thermodynamic results achieved the same result. Histopathology confirmed the liver injury by amoxicillin and the partial repair by the biosystem using ASE. Moreover, electric modulus, related dielectric parameters, and their thermodynamic state functions showed different changes in their values under the effect of amoxicillin. Using ASE helped the biosystem to restore these changes near their control values.","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 5","pages":"tfae175"},"PeriodicalIF":2.2,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11474245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453742","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}

引用次数: 0

4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP) exposure induces hepatotoxicity and nephrotoxicity - role of oxidative stress, mitochondrial dysfunction and pathways of cytotoxicity. 暴露于 4-甲基-2,4-双（4-羟基苯基）戊烯（MBP）会诱发肝毒性和肾毒性--氧化应激、线粒体功能障碍和细胞毒性途径的作用。

IF 2.2 4区医学

Toxicology Research Pub Date : 2024-10-15 eCollection Date: 2024-10-01 DOI: 10.1093/toxres/tfae173

Gobichettipalayam Balasubramaniam Maadurshni, Manikandan Nagarajan, Balamurali Mahalakshmi, Jeganathan Sivasubramanian, Vedagiri Hemamalini, Jeganathan Manivannan

{"title":"4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP) exposure induces hepatotoxicity and nephrotoxicity - role of oxidative stress, mitochondrial dysfunction and pathways of cytotoxicity.","authors":"Gobichettipalayam Balasubramaniam Maadurshni, Manikandan Nagarajan, Balamurali Mahalakshmi, Jeganathan Sivasubramanian, Vedagiri Hemamalini, Jeganathan Manivannan","doi":"10.1093/toxres/tfae173","DOIUrl":"https://doi.org/10.1093/toxres/tfae173","url":null,"abstract":"Objective: Bisphenol A (BPA) is a ubiquitous pollutant worldwide and 4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP) is considered a major active metabolite of BPA with a wide range of potent toxicological properties. However, its adverse outcome pathway (AOP) on the hepatic and renal system has not yet been explored.Methods: Hence, the current study evaluated its effect on cell survival, oxidative stress, and apoptosis. In addition, the influence of signalling pathways on cytotoxicity and ROS generating enzymes (NOX2 and XO) on oxidative stress was explored by siRNA knockdown experiments. Further, its molecular interaction with SOD, CAT, and HSA (molecular docking and dynamics) was evaluated and validated with spectroscopy (fluorescence and FTIR) based methods.Results: The outcome indicates that MBP exposure dose dependently increased the cytotoxic response, oxidative stress, and apoptosis in both hepatocytes and kidney cells. Further, MAPK signalling pathways and oxidative stress influenced the overall cytotoxic response in both cells. In addition, the stimulatory (NOX2 and XO) and inhibitory (SOD and CAT) effects of MBP were observed, along with a robust interaction with HSA.Conclusions: The overall observation illustrates that MBP exposure adversely impacts hepatic and renal cells through oxidative stress and relevant molecular pathways which may connect the missing links during risk assessment of BPA.","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 5","pages":"tfae173"},"PeriodicalIF":2.2,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11474237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453735","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}

引用次数: 0

Design and computational analysis of a novel Leptulipin-p28 fusion protein as a multitarget anticancer therapy in breast cancer. 设计和计算分析新型 Leptulipin-p28 融合蛋白作为乳腺癌的多靶点抗癌疗法。

IF 2.2 4区医学

Toxicology Research Pub Date : 2024-10-13 eCollection Date: 2024-10-01 DOI: 10.1093/toxres/tfae174

Sania Khalid, Hafiz Muhammad Rehman, Yasamin Al-Qassab, Irfan Ahmad, Tehreem Fatima, Mian Muhammad Mubasher, Maria Kalsoom, Tariq Nadeem, Hamid Bashir

{"title":"Design and computational analysis of a novel Leptulipin-p28 fusion protein as a multitarget anticancer therapy in breast cancer.","authors":"Sania Khalid, Hafiz Muhammad Rehman, Yasamin Al-Qassab, Irfan Ahmad, Tehreem Fatima, Mian Muhammad Mubasher, Maria Kalsoom, Tariq Nadeem, Hamid Bashir","doi":"10.1093/toxres/tfae174","DOIUrl":"https://doi.org/10.1093/toxres/tfae174","url":null,"abstract":"The search for novel therapeutic agents to treat breast cancer has compelled the development of fusion proteins that synergize the functional benefits of different bioactive peptides. Leptulipin, derived from scorpion venom, exhibits antitumor properties. On the other hand, p28, a peptide from the bacterial protein azurin, enhances cell penetration. The current study investigated the design and computational evaluation of a Leptulipin-p28 fusion protein for breast cancer treatment. The amino acid sequences of Leptulipin and p28 were joined via a rigid linker to maintain structural and functional integrity. Secondary and tertiary structure predictions were performed using online servers of GOR-IV and I-TASSER. Physicochemical properties and solubility were analyzed using ProtParam and Protein-Sol. Validation and quality assessment of the fusion protein were confirmed through Rampage and ERRAT2. Finally, the fusion protein was docked with 2 receptors (VEGFR and Cadherin) and docked complexes were simulated on GROMACS. The Leptulipin-p28 fusion protein exhibited a stable structure exhibiting a high quality score of 92 on ERRAT and Ramachandran plot analysis highlighting 76.3% of residues in the favorable region. Docking studies with VEGFR and Cadherin receptors followed by 100 ns simulations on GROMACS showed stable complex formation. Molecular dynamics simulations confirmed the stability and robust interaction of the fusion protein-receptor complexes over time. The computational analysis indicates that the Leptulipin-p28 fusion protein holds promise as a multitarget therapeutic agent in breast cancer. The current findings warrant further investigation through in vitro and in vivo studies to validate the current outcomes.","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 5","pages":"tfae174"},"PeriodicalIF":2.2,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11471314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453737","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}

引用次数: 0

HDAC10 inhibits non-small-cell lung cancer cell ferroptosis through the microRNA-223-5p-SLC7A11 axis. HDAC10通过microRNA-223-5p-SLC7A11轴抑制非小细胞肺癌细胞的铁突变。

IF 2.2 4区医学

Toxicology Research Pub Date : 2024-10-13 eCollection Date: 2024-10-01 DOI: 10.1093/toxres/tfae164

Zhihua Shi, Tao Jiang, Xusheng Sun, Liangbiao Peng, Bingji Cao, Yi Wang

{"title":"HDAC10 inhibits non-small-cell lung cancer cell ferroptosis through the microRNA-223-5p-SLC7A11 axis.","authors":"Zhihua Shi, Tao Jiang, Xusheng Sun, Liangbiao Peng, Bingji Cao, Yi Wang","doi":"10.1093/toxres/tfae164","DOIUrl":"https://doi.org/10.1093/toxres/tfae164","url":null,"abstract":"Objective: Non-small-cell lung cancer (NSCLC) is a leading attributor to cancer deaths. High HDAC10 and low microRNA (miR)-223-5p levels have been observed in NSCLC. But their roles remain elusive. This study illustrated their roles in NSCLC cell ferroptosis and the mechanism.Methods: HDAC10, miR-223-5p, and solute carrier family 7 member 11 (SLC7A11) levels in cells were determined by RT-qPCR. Iron ion content, reactive oxygen species (ROS), and glutathione (GSH) levels were tested using reagent kits, and levels of SLC7A11 and Acyl-CoA synthesis long chain family (ACSL4) were examined using Western blot. Chromatin immunoprecision was performed to analyze the enrichment of HDAC10 and acetylated lysine 9 of histone H3 (H3K9ac) on the miR-223-5p promoter. The targeted binding of miR-223-5p and SLC7A11 was analyzed by dual-luciferase assay. Joint experiments were designed to identify the role of miR-223-5p/SLC7A11 axis in HDAC10-regulated ferroptosis in NSCLC cells.Results: HDAC10 was highly expressed in NSCLC cells. Silencing HDAC10 significantly reduced GSH and SLC7A11 levels, upregulated iron ion content, ROS levels, and ACSL4 expression, promoting cell ferroptosis. Mechanically, HDAC10 inhibited miR-223-5p expression through H3K9ac deacetylation of the miR-223-5p promoter, thereby targeting SLC7A11. The joint experimental results showed that overexpression of SLC7A11 or downregulation of miR-223-5p alleviated the promoting effect of silencing HDAC10 on ferroptosis in NSCLC cells.Conclusion: HDAC10 inhibits miR-223-5p expression through H3K9ac deacetylation of the miR-223-5p promoter, thereby promoting SLC7A11 expression and inhibiting ferroptosis in NSCLC cells.","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 5","pages":"tfae164"},"PeriodicalIF":2.2,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11471316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453740","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}

引用次数: 0

Reproductive safety of STING agonists MSA-2 and manganese-MSA-2. STING 激动剂 MSA-2 和锰-MSA-2 的生殖安全性。

IF 2.2 4区医学

Toxicology Research Pub Date : 2024-10-13 eCollection Date: 2024-10-01 DOI: 10.1093/toxres/tfae172

Ya Cai, Tian He, Tao Yang, Yating Li, Lirong Yi, Wenqing Li, Peng Zhou

引用次数: 0

Ephedrine attenuates LPS-induced M1 polarization of alveolar macrophages via the PKM2-mediated glycolysis. 麻黄碱可通过 PKM2 介导的糖酵解减轻 LPS 诱导的肺泡巨噬细胞 M1 极化。

IF 2.2 4区医学

Toxicology Research Pub Date : 2024-10-10 eCollection Date: 2024-10-01 DOI: 10.1093/toxres/tfae166

Yijin Xiang, Zaifeng Jiang, Zhigang Yang, Shaomin Gong, Weiran Niu

{"title":"Ephedrine attenuates LPS-induced M1 polarization of alveolar macrophages via the PKM2-mediated glycolysis.","authors":"Yijin Xiang, Zaifeng Jiang, Zhigang Yang, Shaomin Gong, Weiran Niu","doi":"10.1093/toxres/tfae166","DOIUrl":"https://doi.org/10.1093/toxres/tfae166","url":null,"abstract":"Background: Asthma is one of chronic inflammatory lung diseases in world. The important role of macrophage polarization and glycolysis in lung inflammation has attracted considerable attention. Ephedrine (EP) is a compound isolated from Ephedra and plays a regulatory role in inflammatory response, but its role in asthma and mechanism involved are not clear. Therefore, the purpose of this study was to investigate the molecular mechanism and effect of EP on lipopolysaccharide (LPS)-induced alveolar macrophage polarization and glycolysis.Methods: We investigated the expression of Tnf-a, Nos2, Il10, and Arg1 using RT-PCR, as well as PKM2 and LDHA protein expression with Western blot. A CCK-8 assay was performed to determine the viability of the cells. The extracellular acidification rate (ECAR), ATP and lactate level were detected using commercial kits.Results: The results revealed that EP alleviated LPS-induced NR8383 cell glycolysis and M1 polarization. Further studies found that EP enhanced the effect of 2-DG on NR8383 cell glycolysis and M1 polarization. More importantly, PKM2 inhibitor alleviated LPS-induced NR8383 cell glycolysis and M1 polarization. In addition, EP alleviated LPS-induced NR8383 cell glycolysis and M1 polarization by targeting PKM2.Conclusion: It is suggested that EP alleviates LPS-induced glycolysis and M1 polarization in NR8383 cells by regulating PKM2, thereby alleviating lung injury, suggesting the involvment of alveolar macrophage polarization and glycolysis in the role of EP in asthma.","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 5","pages":"tfae166"},"PeriodicalIF":2.2,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453738","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}

引用次数: 0

Cytotoxicity induced by three commercial neonicotinoid insecticide formulations in differentiated human neuroblastoma SH-SY5Y cells. 三种商用新烟碱类杀虫剂制剂在分化的人神经母细胞瘤 SH-SY5Y 细胞中诱导的细胞毒性。

IF 2.2 4区医学

Toxicology Research Pub Date : 2024-10-10 eCollection Date: 2024-10-01 DOI: 10.1093/toxres/tfae171

Karol Ferreira Honatel, Aline Mocellin Conte, Solange Cristina Garcia, Bruno Dutra Arbo, Marcelo Dutra Arbo

{"title":"Cytotoxicity induced by three commercial neonicotinoid insecticide formulations in differentiated human neuroblastoma SH-SY5Y cells.","authors":"Karol Ferreira Honatel, Aline Mocellin Conte, Solange Cristina Garcia, Bruno Dutra Arbo, Marcelo Dutra Arbo","doi":"10.1093/toxres/tfae171","DOIUrl":"https://doi.org/10.1093/toxres/tfae171","url":null,"abstract":"Background: Neonicotinoid insecticides are used worldwide for crop protection. They act as agonists at postsynaptic nicotinic acetylcholine receptors (nAChRs), disrupting normal neurotransmission in target insects. Human exposure is high due to the widespread use of neonicotinoids and their residues in food. This study aimed to evaluate the in vitro neurotoxicity of three neonicotinoid commercial formulations Much 600 FS® (imidacloprid 600 g L-1), Evidence 700 WG® (imidacloprid 700 g kg-1), and Actara 250 WG® (thiamethoxam 250 g kg-1) in differentiated human neuroblastoma SH-SY5Y cell line.Methods: Cells were incubated with the pesticides for 96 h, and the cytotoxicity was evaluated through the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium·bromide (MTT) reduction and neutral red (NR) uptake assays. Toxicological pathways such as reactive oxygen (ROS) and nitrogen species (RNS) production, mitochondrial membrane potential, cell death mode, and the expression of the pro-apoptotic protein Bax were also evaluated.Results: EC50 values of 266.4, 4,175, and 653.2 mg L-1 were found for Much®, Evidence® and Actara®, respectively. Significant increases in ROS and RNS generation were observed for all pesticides, while mitochondrial membrane potential and Bax protein expression showed no significant changes. Analysis of cell death mode revealed an increase in early apoptotic cells.Conclusion: Therefore, neonicotinoid insecticides are potentially neurotoxic, reinforcing concerns about human exposure to these commercial formulations.","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 5","pages":"tfae171"},"PeriodicalIF":2.2,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453736","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}

引用次数: 0

Repeated radon exposure induced ATM kinase-mediated DNA damage response and protective autophagy in mice and human bronchial epithelial cells. 反复氡照射诱导小鼠和人类支气管上皮细胞发生 ATM 激酶介导的 DNA 损伤反应和保护性自噬。

IF 2.2 4区医学

Toxicology Research Pub Date : 2024-10-07 eCollection Date: 2024-10-01 DOI: 10.1093/toxres/tfae165

Xiaoyu Chen, Shan Shan, Aiqing Wang, Cheng Tu, Jianmei Wan, Chengjiao Hong, Xiaohan Li, Xueying Wang, Jieyun Yin, Jian Tong, Hailin Tian, Lili Xin

{"title":"Repeated radon exposure induced ATM kinase-mediated DNA damage response and protective autophagy in mice and human bronchial epithelial cells.","authors":"Xiaoyu Chen, Shan Shan, Aiqing Wang, Cheng Tu, Jianmei Wan, Chengjiao Hong, Xiaohan Li, Xueying Wang, Jieyun Yin, Jian Tong, Hailin Tian, Lili Xin","doi":"10.1093/toxres/tfae165","DOIUrl":"https://doi.org/10.1093/toxres/tfae165","url":null,"abstract":"Objective: Radon ( 222 Rn) is a naturally occurring radioactive gas that has been closely linked with the development of lung cancer. In this study, we investigated the radon-induced DNA strand breaks, a critical event in lung carcinogenesis, and the corresponding DNA damage response (DDR) in mice and human bronchial epithelial (BEAS-2B) cells.Methods: Biomarkers of DNA double-strand breaks (DSBs), DNA repair response to DSBs, ataxia-telangiectasia mutated (ATM) kinase, autophagy, and a cell apoptosis signaling pathway as well as cell-cycle arrest and the rate of apoptosis were determined in mouse lung and BEAS-2B cells after radon exposure.Results: Repeated radon exposure induced DSBs indicated by the increasing expressions of γ-Histone 2AX (H2AX) protein and H2AX gene in a time and dose-dependent manner. Additionally, a panel of ATM-dependent repair cascades [i.e. non-homologous DNA end joining (NHEJ), cell-cycle arrest and the p38 mitogen activated protein kinase (p38MAPK)/Bax apoptosis signaling pathway] as well as the autophagy process were activated. Inhibition of autophagy by 3-methyladenine pre-treatment partially reversed the expression of NHEJ-related genes induced by radon exposure in BEAS-2B cells.Conclusions: The findings demonstrated that long-term exposure to radon gas induced DNA lesions in the form of DSBs and a series of ATM-dependent DDR pathways. Activation of the ATM-mediated autophagy may provide a protective and pro-survival effect on radon-induced DSBs.","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 5","pages":"tfae165"},"PeriodicalIF":2.2,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11457374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386487","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}

引用次数: 0

Proteomic analysis of toxic effects of short-term cadmium exposure on goat livers. 短期镉暴露对山羊肝脏毒性效应的蛋白质组分析

IF 2.2 4区医学

Toxicology Research Pub Date : 2024-10-07 eCollection Date: 2024-10-01 DOI: 10.1093/toxres/tfae162

Guangyang Liu, Xiaoyun Shen, Yuanfeng Li

{"title":"Proteomic analysis of toxic effects of short-term cadmium exposure on goat livers.","authors":"Guangyang Liu, Xiaoyun Shen, Yuanfeng Li","doi":"10.1093/toxres/tfae162","DOIUrl":"https://doi.org/10.1093/toxres/tfae162","url":null,"abstract":"Food safety is closely related to environmental pollution. It is worth noting that the long-term accumulation of Cd, a toxic heavy metal, in animals may pose a threat to human health through food chain. Previous studies have found that Cd exposure may cause liver metabolic disorders of black goats, but the mechanism of its impact on liver proteome of goats has not been widely studied. Therefore, in this study, ten male goats (Nubian black goat × native black goat) were exposed to Cd via drinking water containing CdCl2 (20 mg Cd·kg - 1·BW) for 30 days (five male goats per group). Blood physiology and liver antioxidant indices in black goats were determined and differentially expressed proteins (DEPs) in the livers of Cd-exposed goats were profiled by using TMT-labelled proteomics. It was found that plasma Hb and RBC levels as well as PCV values were decreased, liver SOD, GSH-Px, T-AOC and CAT levels were decreased, and MDA level was increased in Cd-treated goats, and 630 DEPs (up 326, down 304) in the livers of Cd-treated goats. Proteomics analysis revealed that Cd exposure affected glutathione metabolism and drug metabolism-cytochrome P450. We identified GP×2, GSTM3, and TBXAS1 as potential protein markers of early Cd toxicity in goats. This study provided theoretical basis for early diagnosis of Cd poisoning in goats.","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 5","pages":"tfae162"},"PeriodicalIF":2.2,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11457375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386486","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}

引用次数: 0