Toxicology and Industrial Health最新文献_第2页

Activation of Ferroptosis and NF-κB/NLRP3/MAPK Pathways in Methylmercury-Induced Hepatotoxicity. 甲基汞诱导的肝毒性中铁下垂和NF-κB/NLRP3/MAPK通路的激活

IF 1.7 4区医学

Toxicology and Industrial Health Pub Date : 2025-03-01 Epub Date: 2024-12-13 DOI: 10.1177/07482337241307067

Yueqing Xie, Hongsen Yu, Yingrong Ye, Jingjing Wang, Zhengtao Yang, Ershun Zhou

{"title":"Activation of Ferroptosis and NF-κB/NLRP3/MAPK Pathways in Methylmercury-Induced Hepatotoxicity.","authors":"Yueqing Xie, Hongsen Yu, Yingrong Ye, Jingjing Wang, Zhengtao Yang, Ershun Zhou","doi":"10.1177/07482337241307067","DOIUrl":"10.1177/07482337241307067","url":null,"abstract":"Methylmercury (MeHg) is a potent hepatotoxin with a complex mechanism of inducing liver injury. Ferroptosis, an iron-dependent form of non-apoptotic cell death, is implicated in various toxicological responses, but its role in MeHg-induced liver damage remains under investigation. In this study, we established an acute liver injury (ALI) model in mice via gavage of MeHg (0, 40, 80, 160 μmol/kg). Histopathological analysis revealed dose-dependent liver damage, corroborated by elevated serum biochemical markers, confirming MeHg-induced hepatotoxicity. MeHg exposure raised MDA levels, inhibited SOD and GSH activity, and downregulated CAT expression. Increased iron accumulation and elevated transferrin receptor expression were observed, alongside decreased GPX4 and SLC7A11 levels, indicating ferroptosis involvement. Additionally, inflammation in MeHg-exposed livers was markedly intensified, as evidenced by increased MPO activity, upregulation of pro-inflammatory cytokines, and activation of the NF-κB/NLRP3 signaling pathway. The Keap1/NRF2/HO-1 oxidative stress response pathway was significantly activated, and p38/ERK1/2 MAPK signaling was notably increased. These findings suggested that MeHg induced acute liver injury through the interplay of ferroptosis, oxidative stress, inflammation, and MAPK signaling pathways, providing a scientific basis for future exploration of the mechanisms underlying MeHg-induced hepatotoxicity and potential therapeutic strategies.","PeriodicalId":23171,"journal":{"name":"Toxicology and Industrial Health","volume":" ","pages":"131-139"},"PeriodicalIF":1.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822567","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

Case series and clinical analysis of acute hydrogen sulfide poisoning: Experience from 10 cases at a hospital in Zhoushan. 舟山某医院急性硫化氢中毒10例病例分析及临床分析

IF 1.7 4区医学

Toxicology and Industrial Health Pub Date : 2025-03-01 Epub Date: 2024-12-20 DOI: 10.1177/07482337241308388

Yuechuan Shen, Guangfen Zhao, Jingkai Lin, Junyan Wang, Bin Luo, Jingye Liu, Yini Zhang, Junhua Huang

{"title":"Case series and clinical analysis of acute hydrogen sulfide poisoning: Experience from 10 cases at a hospital in Zhoushan.","authors":"Yuechuan Shen, Guangfen Zhao, Jingkai Lin, Junyan Wang, Bin Luo, Jingye Liu, Yini Zhang, Junhua Huang","doi":"10.1177/07482337241308388","DOIUrl":"10.1177/07482337241308388","url":null,"abstract":"This study investigated the etiology, clinical features, and management of acute hydrogen sulfide (H2S) poisoning in Zhoushan. A retrospective analysis was conducted on 10 patients admitted to our hospital between August and September 2023 due to two incidents of acute H2S poisoning. The first incident involved fishermen working in a fishing cabin (6 patients), while the second involved sanitation workers during sewer maintenance (4 patients). Among the patients, 4 had severe poisoning, 3 had moderate poisoning, and 3 had mild poisoning. Corneal chemical injuries were observed in 4 severe patients, and chest CT scans showed bilateral infiltrative changes in 7 patients. Elevated lactate concentrations, and low oxygenation indices were noted in all severe patients. Severe cases received intensive care, including tracheal intubation, mechanical ventilation, corticosteroids, methylene blue, ulinastatin, and hyperbaric oxygen therapy. Patients with mild to moderate symptoms received supportive treatments, including oxygen therapy and hyperbaric oxygen therapy. With the exception of one fatality, all other patients were discharged after successful treatment. Fishing boat cabins and decomposed sewage channels in island areas are common sites for acute H2S poisoning. Rapid identification of H2S poisoning and evaluation are crucial. Early airway management is essential for severe cases to prevent vital organ hypoxia.","PeriodicalId":23171,"journal":{"name":"Toxicology and Industrial Health","volume":" ","pages":"151-162"},"PeriodicalIF":1.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865506","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

Perfluorooctane sulfonate causes HK-2 cell injury through ferroptosis and endoplasmic reticulum stress pathways. 全氟辛烷磺酸通过铁突变和内质网应激途径导致 HK-2 细胞损伤

IF 1.7 4区医学

Toxicology and Industrial Health Pub Date : 2025-02-01 Epub Date: 2024-11-19 DOI: 10.1177/07482337241300722

Shuqi Yan, Haoyan Ma, Yuwan Ren, Pingwei Wang, Dongge Liu, Na Ding, Yanping Liu, Qianqian Chen, Shuping Ren, Yan Mou

{"title":"Perfluorooctane sulfonate causes HK-2 cell injury through ferroptosis and endoplasmic reticulum stress pathways.","authors":"Shuqi Yan, Haoyan Ma, Yuwan Ren, Pingwei Wang, Dongge Liu, Na Ding, Yanping Liu, Qianqian Chen, Shuping Ren, Yan Mou","doi":"10.1177/07482337241300722","DOIUrl":"10.1177/07482337241300722","url":null,"abstract":"Perfluorooctane sulfonate (PFOS) is a synthetic persistent organic compound that is widely used in industrial products. Studies have shown that PFOS can accumulate in environment and pose a threat to human health. As the kidney is the main excretory organ for PFOS, it is important to study PFOS damage to the kidney to investigate its toxicity. Human proximal tubular epithelial cells (HK-2) were treated with 200 μM PFOS or 1 μM Fer-1. Cell viability, the levels of MDA, GSH, intracellular iron ion, and GPX-4 were determined. The expression of KIM-1 and endoplasmic reticulum stress (ERS) related proteins were determined. The expression levels of KIM-1, a marker of renal tubular injury, and ERS-related proteins, GRP78, ATF6, IRE1, and PERK, were significantly increased in HK-2 cells exposed to PFOS. The levels of MDA and intracellular total iron ion also were significantly increased in HK-2 cells exposed to PFOS and the levels of GSH and GPX-4 were significantly decreased. PFOS can damage HK-2 cells through ferroptosis and endoplasmic reticulum stress, which provides a theoretical foundation for exploring the toxicity of PFOS to the kidney.","PeriodicalId":23171,"journal":{"name":"Toxicology and Industrial Health","volume":" ","pages":"73-82"},"PeriodicalIF":1.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668049","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

Wnt5a promotes Kupffer cell activation in trichloroethylene-induced immune liver injury. 在三氯乙烯诱导的免疫性肝损伤中，Wnt5a促进了Kupffer细胞的活化。

IF 1.7 4区医学

Toxicology and Industrial Health Pub Date : 2025-02-01 Epub Date: 2024-11-26 DOI: 10.1177/07482337241300953

Lei Gao, Ya-Ni Ding, Peng-Cheng Zhou, Luo-Lun Dong, Xin-Yu Peng, Yi-Ru Tang, Qi-Xing Zhu, Jia-Xiang Zhang

{"title":"Wnt5a promotes Kupffer cell activation in trichloroethylene-induced immune liver injury.","authors":"Lei Gao, Ya-Ni Ding, Peng-Cheng Zhou, Luo-Lun Dong, Xin-Yu Peng, Yi-Ru Tang, Qi-Xing Zhu, Jia-Xiang Zhang","doi":"10.1177/07482337241300953","DOIUrl":"10.1177/07482337241300953","url":null,"abstract":"Trichloroethylene (TCE) is a volatile, colorless liquid that is widely used as a chlorinated organic vehicle in industrial production and processing industries. Many workers exposed to trichloroethylene may develop trichloroethylene hypersensitivity syndrome (THS). However, the underlying mechanism of THS is still unclear, especially liver injury. The present study aimed to investigate whether Wnt5a/c-Jun N-terminal kinase (JNK) is involved in and regulates liver injury caused by TCE exposure and to provide new directions for the prevention and treatment in clinical settings of liver injury caused by TCE exposure. We used 6- to 8-week-old SPF-grade BALB/c female mice to establish a TCE sensitization model and explored the mechanism through inhibitor intervention. We found that the expression of Wnt5a/JNK was significantly elevated in the liver of TCE sensitization-positive mice. Inhibitors of Wnt Production 2 (IWP-2) are known antagonists of the Wnt pathway. TCE-sensitization mice treated with IWP-2 showed downregulated Wnt5a/JNK expression, reduced Kupffer cell activation, and decreased liver injury. At the same time, we found that phosphorylated JNK in TCE-sensitization mouse livers and extracted Kupffer cells showed a significant downward trend after inhibition of Wnt5a function. We also found that a specific JNK inhibitor, SP600125, decreased the secretion of cytokines and chemokines and decreased Kupffer cell activation. We demonstrated that Wnt5a/JNK was involved in the regulation of liver injury in TCE-sensitization mice and that it exacerbated liver injury by activating Kupffer cells and releasing chemokines. We therefore hypothesized that Kupffer cell activation was affected by JNK, which reduced chemokine and cytokine secretion and attenuated liver injury in TCE-sensitization mice.","PeriodicalId":23171,"journal":{"name":"Toxicology and Industrial Health","volume":" ","pages":"83-96"},"PeriodicalIF":1.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142717161","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

Metabolomics reveals that phosphatidylethanolamine can alleviate the toxicity of silica nanoparticles in human lung A549 cells. 代谢组学研究表明，磷脂酰乙醇胺可减轻二氧化硅纳米颗粒对人肺A549细胞的毒性。

IF 1.7 4区医学

Toxicology and Industrial Health Pub Date : 2025-02-01 Epub Date: 2024-11-29 DOI: 10.1177/07482337241304166

Shuang Chen, Chengzhi Liu, Yifan Yang, Jiangliang Chu, Beilei Yuan, Zhe Wang

{"title":"Metabolomics reveals that phosphatidylethanolamine can alleviate the toxicity of silica nanoparticles in human lung A549 cells.","authors":"Shuang Chen, Chengzhi Liu, Yifan Yang, Jiangliang Chu, Beilei Yuan, Zhe Wang","doi":"10.1177/07482337241304166","DOIUrl":"10.1177/07482337241304166","url":null,"abstract":"Silica nanoparticles (SiNPs) are widely utilized in occupational settings where they can cause lung damage through inhalation. The objective of this research was to explore the metabolic markers of SiNPs-induced toxicity on A549 cells by metabolomics and provide a foundation for studying nanoparticle-induced lung toxicity. Metabolomics analysis was employed to analyze the metabolites of SiNPs-treated A549 cells. LASSO regression was applied for selection, and protective measure experiments were conducted to validate the efficacy of selected potential toxicity mitigators. After SiNPs treatment, 23 differential metabolites were identified, including lipids, nucleotides, and organic oxidants. Pathway analysis revealed involvement in various biological processes. LASSO regression further identified six metabolites significantly associated with SiNPs toxicity. Notably, phosphatidylethanolamine (PE (14:1(9Z)/14:0)) showed enrichment in six significant metabolic pathways and with an AUC of 1 in the ROC curve. Protective measure experiments verified its protective effect on A549 cells and demonstrated its considerable inhibition of SiNPs-induced cytotoxicity. This study elucidated SiNPs-induced cytotoxicity on A549 cells and identified PE as a potential toxicity mitigator. These findings contribute to understanding the mechanisms of nanoparticle-induced lung toxicity and inform occupational health preventive strategies.","PeriodicalId":23171,"journal":{"name":"Toxicology and Industrial Health","volume":" ","pages":"97-107"},"PeriodicalIF":1.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755636","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

Transcriptome analysis reveals the molecular mechanisms of neonicotinoid acetamiprid in Leydig cells. 转录组分析揭示了新烟碱啶虫脒在睾丸细胞中的分子机制。

IF 1.7 4区医学

Toxicology and Industrial Health Pub Date : 2025-02-01 Epub Date: 2024-11-11 DOI: 10.1177/07482337241300215

Xun Liu, Ce Wang, Yue Ma, Linxiang Fu, Wanji Luo, Changjie Xu, Ying Tian, Mingyue Ma, Yaping Mao

{"title":"Transcriptome analysis reveals the molecular mechanisms of neonicotinoid acetamiprid in Leydig cells.","authors":"Xun Liu, Ce Wang, Yue Ma, Linxiang Fu, Wanji Luo, Changjie Xu, Ying Tian, Mingyue Ma, Yaping Mao","doi":"10.1177/07482337241300215","DOIUrl":"10.1177/07482337241300215","url":null,"abstract":"At present, the reproductive toxicology of neonicotinoids has received greater attention, however, its potential mechanisms are still not fully understood. Acetamiprid (ACE) is a new-generation neonicotinoid and has become a ubiquitous contaminant in the environment. This study aimed to investigate the toxic effects of ACE in TM3 Leydig cells based on transcriptome analysis. The viability and apoptosis of TM3 cells exposed to different concentrations of ACE were assessed by CCK8 and flow cytometry, respectively. After ACE exposure, transcriptome analysis was performed to screen differential expression genes (DEGs), followed by qPCR verification. Results showed that ACE exposure resulted in a time- and dose-dependent decrease in the viability of TM3 cells (p < .05). ACE also exerted a dose-dependent pro-apoptotic effect on TM3 cells. Results of RNA-seq showed that 1477 DEGs were obtained, of which 539 DEGs were up-regulated and 938 DEGs were down-regulated. GO and KEGG analyses of DEGs showed that DNA replication and cell cycle might be the key mechanisms for the cytotoxicity of ACE. qPCR results demonstrated that Mdm2, Cdkn1a (p21) and Gadd45 were significantly increased, and Pcna, Ccna2 (CycA), Ccnb1 (CycB), Ccne1 (CycE), and Cdk1 were significantly decreased, indicating that ACE exposure might promote G1/S and G2/M cell cycle arrest. Additionally, FoxO, p53, and HIF-1 signaling pathways and ferroptosis might play important roles in ACE-induced reproductive toxicity. Collectively, this study provides new perspectives into the mechanism of ACE-induced reproductive toxicity and lays a theoretical foundation for the in-depth study of non-target toxicity mechanisms of neonicotinoid insecticides.","PeriodicalId":23171,"journal":{"name":"Toxicology and Industrial Health","volume":" ","pages":"61-72"},"PeriodicalIF":1.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628737","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

DEHP impairs the oxidative stress response and disrupts trace element and mineral metabolism within the mitochondria of detoxification organs. DEHP 会损害氧化应激反应，破坏解毒器官线粒体内微量元素和矿物质的新陈代谢。

IF 1.7 4区医学

Toxicology and Industrial Health Pub Date : 2025-02-01 Epub Date: 2024-12-09 DOI: 10.1177/07482337241306252

Duygu Aydemir, Gozde Karabulut, Nurhayat Barlas, Nuriye Nuray Ulusu

{"title":"DEHP impairs the oxidative stress response and disrupts trace element and mineral metabolism within the mitochondria of detoxification organs.","authors":"Duygu Aydemir, Gozde Karabulut, Nurhayat Barlas, Nuriye Nuray Ulusu","doi":"10.1177/07482337241306252","DOIUrl":"10.1177/07482337241306252","url":null,"abstract":"Di(2-ethylhexyl) phthalate (DEHP), a widely utilized plasticizer in various consumer products, is classified as an endocrine disruptor and has been implicated in numerous adverse health effects, including oxidative stress, inflammation, and metabolic disturbances. Despite the growing body of literature addressing the systemic effects of DEHP, the specific influence of DEHP-induced oxidative stress on mitochondrial function within detoxification organs, particularly the liver and kidneys, remains largely unexplored. This study evaluated the effects of DEHP exposure (0, 100, 200, and 400 mg/kg/day) on mitochondrial oxidative stress, trace elements, and mineral metabolism associated with signaling pathways in the liver and kidneys of rats. Altered mitochondrial oxidative stress status was indicated by impaired glucose 6-phosphate dehydrogenase (G6PD), 6-phosphoglucerate dehydrogenase (6-PGD), glutathione reductase (GR), glutathione s-transferase (GST), and glutathione peroxidase (GPx) activities, along with significant disruptions in essential minerals and trace elements, including Na, Mg, Cu, Zn, and Fe. Key oxidative stress signaling pathways, such as NF-κB, Akt, STAT3, and CREB, glucose, and tissue homeostasis, displayed dose-dependent responses to DEHP, indicating complex regulatory mechanisms. This study represents the first comprehensive investigation into DEHP-induced mitochondrial dysfunction, highlighting its effects on oxidative stress metabolism, trace element homeostasis, and cellular signaling pathways in detoxification organs. These findings provide novel insights into the mitochondrial mechanisms underlying DEHP toxicity and underscores the need for further research into the implications of plasticizer exposure on human health.","PeriodicalId":23171,"journal":{"name":"Toxicology and Industrial Health","volume":" ","pages":"108-121"},"PeriodicalIF":1.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802157","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

Methyltrimethoxysilane (MTMS).

IF 1.7 4区医学

Toxicology and Industrial Health Pub Date : 2025-01-30 DOI: 10.1177/07482337241301523

{"title":"Methyltrimethoxysilane (MTMS).","authors":"","doi":"10.1177/07482337241301523","DOIUrl":"https://doi.org/10.1177/07482337241301523","url":null,"abstract":"Methyltrimethoxysilane (MTMS) has been used as a coupling agent in thermoplastics and thermosetting resins, a cross-linker in silicone sealants, a water repellent component, and in silicone hard-coats for plastics. Acute studies in experimental animals showed a low order of toxicity for MTMS via oral, dermal, and inhalation routes. MTMS was slightly irritating to both eyes and skin in rabbits. A weight of evidence assessment supports that MTMS is not a dermal sensitizer. Available in vitro and in vivo assays indicated MTMS has a low potential for genotoxicity. MTMS did not produce any changes in either reproductive or developmental parameters. Short-term, repeated inhalation in rats produced treatment-related observations in the urinary bladder and kidney. In a 90-day inhalation study in rats, MTMS was associated with production of urinary bladder epithelial hyperplasia, calculi formation, and moderate kidney dilation with hyperplasia of the pelvic epithelium and granulomatous inflammation. However, an expert panel review concluded that changes in the bladder and kidney were adaptive responses to physical or chemical irritation. The NOAEL of 100 ppm (557 mg/m3) from the 90-day inhalation study was considered the point of departure for the health-based WEEL derivation. After adjusting to account for duration of exposure and interindividual variability, the resulting 8-h TWA WEEL value of 10 ppm (55 mg/m3) is fully expected to provide a significant margin of safety against potential adverse health effects in workers.","PeriodicalId":23171,"journal":{"name":"Toxicology and Industrial Health","volume":" ","pages":"7482337241301523"},"PeriodicalIF":1.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068205","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

Citreoviridin induces apoptosis through oxidative damage and inflammatory response in PC-12 cells. 西曲韦啶通过氧化损伤和炎症反应诱导 PC-12 细胞凋亡

IF 1.7 4区医学

Toxicology and Industrial Health Pub Date : 2025-01-01 Epub Date: 2024-10-22 DOI: 10.1177/07482337241295474

Jing Yang, Jiaojiao Lu, Luoyuan Cao, Wenxu Dong, Xian Zheng, Xianguo Fu

{"title":"Citreoviridin induces apoptosis through oxidative damage and inflammatory response in PC-12 cells.","authors":"Jing Yang, Jiaojiao Lu, Luoyuan Cao, Wenxu Dong, Xian Zheng, Xianguo Fu","doi":"10.1177/07482337241295474","DOIUrl":"10.1177/07482337241295474","url":null,"abstract":"Citreoviridin (CIT) is a mycotoxin produced by various fungi. Although CIT has been reported to cause neurotoxicity, the molecular mechanism is poorly understood. Therefore, the aim of this study was to investigate the effects and molecular mechanisms of CIT in neurotoxicity. Different concentrations of CIT were treated to rat pheochromocytoma (PC-12 cells), and oxidative stress parameters, cytokine levels, and cell apoptosis were evaluated. CIT treatment (5 and 10 μM) significantly induced PC-12 cell apoptosis and increased lactate dehydrogenase activity. Additionally, CIT treatment induced oxidative stress, as evidenced by a significant increase in intracellular levels of reactive oxygen species, malondialdehyde, and superoxide dismutase and a decrease in glutathione activity. Moreover, CIT treatment induced an inflammatory response, as evidenced by a significant increase in the intracellular levels of the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1-beta in PC-12 cells. Furthermore, quantitative PCR and western blotting showed that CIT treatment increased both the protein and mRNA expression of GADD45α and p21 in PC-12 cells, suggesting that CIT may induce apoptosis by inhibiting cell cycle, blocking cell growth, and damaging DNA. Conclusively, this study contributes the understanding the toxicity mechanisms of CIT to nerve cells.","PeriodicalId":23171,"journal":{"name":"Toxicology and Industrial Health","volume":" ","pages":"32-39"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508636","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 silico occupational exposure banding framework for data poor compounds in biotechnology. 生物技术中数据贫乏化合物的硅学职业接触带框架。

IF 1.7 4区医学

Toxicology and Industrial Health Pub Date : 2025-01-01 Epub Date: 2024-10-06 DOI: 10.1177/07482337241289184

Andrey Massarsky, Ernest S Fung, Veneese Jb Evans, Andrew Maier

{"title":"In silico occupational exposure banding framework for data poor compounds in biotechnology.","authors":"Andrey Massarsky, Ernest S Fung, Veneese Jb Evans, Andrew Maier","doi":"10.1177/07482337241289184","DOIUrl":"10.1177/07482337241289184","url":null,"abstract":"Occupational exposure limits (OELs) and occupational exposure bands (OEBs) provide quantitative benchmarks for worker health protection. If empirical toxicology data are insufficient to derive an OEL, an OEB is often assigned using partial toxicology data along with other relevant hazard information. There is no consensus methodology to assign OEBs for chemicals lacking any empirical toxicology data. Thus, this study developed an in silico framework for OEB assignment of data poor compounds. It relies upon computational tools to evaluate standard toxicological end points and to assign reliability ratings, which are then used to assign Global Harmonization System (GHS) hazard categories. Subsequently, the hazard categories are entered into the National Institute for Occupational Safety and Health (NIOSH) occupational exposure banding tool to assign bands for individual end points as well as an overall OEB. As a proof-of-concept, five compounds with established OELs (i.e., \"knowns\") were evaluated. The knowns were assigned to overall OEBs C, D, or E, four of which were equal to or lower than the OEBs based on actual harmonized GHS categories as well as established OELs, indicating that the OEBs assigned using this framework are likely to be protective. Subsequently, five compounds with little to no experimental data and no established OELs from any U.S. agency or consensus OEL-setting organizations were evaluated (i.e., \"unknowns\"). The unknowns were assigned to overall OEBs D or E. It was concluded that the proposed framework can be used to assign protective OEBs to compounds with little to no toxicology testing data. As additional data become available, the compound may be de-risked, and a precautionary OEB (or an OEL) can be assigned. The proposed framework provides an example of a practical methodology to evaluate data poor compounds and shows that the output of this framework is expected to be protective of worker health.","PeriodicalId":23171,"journal":{"name":"Toxicology and Industrial Health","volume":" ","pages":"20-31"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381703","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