Environmental Toxicology最新文献

{"title":"ERα Coregulator TRIM28 Promotes Breast Cancer Progression by Activating the AKT/GSK3β Pathway","authors":"Linlin Fu,&nbsp;Baodong Ma,&nbsp;Lan Zhang,&nbsp;Huikang Xu,&nbsp;Wei Chen,&nbsp;Di Wu,&nbsp;Feng Gao,&nbsp;Yanping Huo","doi":"10.1002/tox.24373","DOIUrl":"10.1002/tox.24373","url":null,"abstract":"<div>\u0000 \u0000 <p>Estrogen receptor α (ERα) promotes the growth and survival of ER-positive breast cancer (BC) cells. ER regulates ER expression target genes by directly binding to specific estrogen response elements, upon activation by estrogens. In this study, 106 proteins interacting with endogenous chromatin-bound ER in a BC cell line MCF7 were identified using the RIME method. The interactome data showed that the tripartite motif containing 28 (TRIM28) is the most significantly enriched ER-associated protein. This study provides evidence that TRIM28 expression improves ER transcriptional activity and promotes the BC cells proliferation, migration, and invasion of BC cells. The high expression of TRIM28 is associated with poor clinical outcomes in patients with ER-positive BC. Mechanistic experiments indicate that TRIM28 expression activates the AKT/GSK3β pathway. To conclude, TRIM28 acts as a regulatory protein of ER and AKT signaling; therefore, it can be a target for the therapeutic interventions of BC.</p>\u0000 </div>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"39 11","pages":"5162-5172"},"PeriodicalIF":4.4,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced IGF-IIRα Expression Exacerbates Lipopolysaccharide-Induced Cardiac Inflammation, Hypertrophy, and Apoptosis Through Calcineurin Activation","authors":"Khwanchit Boonha,&nbsp;Wei-Wen Kuo,&nbsp;Bruce Chi-Kang Tsai,&nbsp;Dennis Jine-Yuan Hsieh,&nbsp;Kuan-Ho Lin,&nbsp;Shang-Yeh Lu,&nbsp;Chia-Hua Kuo,&nbsp;Liang-Yo Yang,&nbsp;Chih-Yang Huang","doi":"10.1002/tox.24385","DOIUrl":"10.1002/tox.24385","url":null,"abstract":"<div>\u0000 \u0000 <p>Cardiovascular disease is one of the leading causes of death worldwide and has a high prevalence. Insulin-like growth factor-II receptor α (IGF-IIRα) acts as a stress-inducible negative regulator. This study focused on the substantial impact of heightened expression of IGF-IIRα in cardiac myoblasts and its association with the exacerbation of cardiac dysfunction. Using lipopolysaccharide (LPS)-induced H9c2 cardiac myoblasts as a model for sepsis, we aimed to elucidate the molecular interactions between IGF-IIRα and LPS in exacerbating cardiac injury. Our findings demonstrated a synergistic induction of cardiac inflammation and hypertrophy by LPS stimulation and IGF-IIRα overexpression, leading to decreased cell survival. Excessive calcineurin activity, triggered by this combined condition, was identified as a key factor exacerbating the negative effects on cell survival. Cellular changes such as cell enlargement, disrupted actin filaments, and upregulation of hypertrophy-related and inflammation-related proteins contributed to the overall hypertrophic and inflammatory responses. Overexpression of IGF-IIRα also exacerbated apoptosis induced by LPS in H9c2 cardiac myoblasts. Inhibiting calcineurin in LPS-treated H9c2 cardiac myoblasts with IGF-IIRα overexpression effectively reversed the detrimental effects, reducing cell damage and mitigating apoptosis-related cardiac mechanisms. Our study suggests that under sepsis-like conditions in the heart with IGF-IIRα overexpression, hyperactivation of calcineurin worsens cardiac damage. Suppressing IGF-IIRα and calcineurin expression could be a potential intervention to alleviate the impact of the illness and improve cardiac function.</p>\u0000 </div>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"39 11","pages":"5173-5186"},"PeriodicalIF":4.4,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rhodiola and Salidroside Attenuate Oxidative Stress-Triggered H9c2 Cardiomyoblast Apoptosis Through IGF1R-Induced ERK1/2 Activation","authors":"I-Ju Ju,&nbsp;Bruce Chi-Kang Tsai,&nbsp;Wei-Wen Kuo,&nbsp;Chia-Hua Kuo,&nbsp;Yueh-Min Lin,&nbsp;Dennis Jine-Yuan Hsieh,&nbsp;Pei-Ying Pai,&nbsp;Shang-En Huang,&nbsp;Shang-Yeh Lu,&nbsp;Shin-Da Lee,&nbsp;Chih-Yang Huang","doi":"10.1002/tox.24372","DOIUrl":"10.1002/tox.24372","url":null,"abstract":"<div>\u0000 \u0000 <p>Oxidative stress is a pivotal factor in the pathogenesis of various cardiovascular diseases. <i>Rhodiola</i>, a traditional Chinese medicine, is recognized for its potent antioxidant properties. Salidroside, a phenylpropanoid glycoside derived from <i>Rhodiola rosea</i>, has shown remarkable antioxidant capabilities. This study aimed to elucidate the potential protective mechanisms of <i>Rhodiola</i> and salidroside against H₂O₂-induced cardiac apoptosis in H9c2 cardiomyoblast cells. H9c2 cells were exposed to H₂O₂ for 4 h, and subsequently treated with <i>Rhodiola</i> or salidroside for 24 h. Cell viability and apoptotic pathways were assessed. The involvement of insulin-like growth factor 1 receptor (IGF1R) and the activation of extracellular regulated protein kinases 1/2 (ERK1/2) were investigated. H₂O₂ (100 μM) exposure significantly induced cardiac apoptosis in H9c2 cells. However, treatment with <i>Rhodiola</i> (12.5, 25, and 50 μg/mL) and salidroside (0.1, 1, and 10 nM) effectively attenuated H₂O₂-induced cytotoxicity and apoptosis. This protective effect was associated with IGF1R-activated phosphorylation of ERK1/2, leading to the inhibition of Fas-dependent proteins, HIF-1α, Bax, and Bak expression in H9c2 cells. The images from hematoxylin and eosin staining and immunofluorescence assays also revealed the protective effects of <i>Rhodiola</i> and salidroside in H9c2 cells against oxidative damage. Our findings suggest that <i>Rhodiola</i> and salidroside possess antioxidative properties that mitigate H₂O₂-induced apoptosis in H9c2 cells. The protective mechanisms involve the activation of IGF1R and subsequent phosphorylation of ERK1/2. These results propose <i>Rhodiola</i> and salidroside as potential therapeutic agents for cardiomyocyte cytotoxicity and apoptosis induced by oxidative stress in heart diseases. Future studies may explore their clinical applications in cardiac health.</p>\u0000 </div>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"39 11","pages":"5150-5161"},"PeriodicalIF":4.4,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective Effects of Carvacrol on Mercuric Chloride-Induced Lung Toxicity Through Modulating Oxidative Stress, Apoptosis, Inflammation, and Autophagy","authors":"Berna Eriten,&nbsp;Sefa Kucukler,&nbsp;Cihan Gur,&nbsp;Adnan Ayna,&nbsp;Halit Diril,&nbsp;Cuneyt Caglayan","doi":"10.1002/tox.24397","DOIUrl":"10.1002/tox.24397","url":null,"abstract":"<p>Mercuric chloride (HgCl₂) is extremely toxic to both humans and animals. It could be absorbed via ingestion, inhalation, and skin contact. Exposure to HgCl₂ can cause severe health effects, including damages to the gastrointestinal, respiratory, and central nervous systems. The purpose of this work was to explore if carvacrol (CRV) could protect rats lungs from damage caused by HgCl₂. Intraperitoneal injections of HgCl₂ at a dose of 1.23 mg/kg body weight were given either alone or in conjunction with oral CRV administration at doses of 25 and 50 mg/kg body weight for 7 days. The study included biochemical and histological techniques to examine the lung tissue's oxidative stress, apoptosis, inflammation, and autophagy processes. HgCl₂-induced reductions in GSH levels and antioxidant enzymes (SOD, CAT, and GPx) activity were enhanced by CRV co-administration. Furthermore, MDA levels were lowered by CRV. The inflammatory mediators NF-κB, IκB, NLRP3, TNF-α, IL-1β, IL6, COX-2, and iNOS were all reduced by CRV. When exposed to HgCl₂, the levels of apoptotic Bax, caspase-3, Apaf1, p53, caspase-6, and caspase-9 increased, but the levels of antiapoptotic Bcl-2 reduced after CRV treatment. CRV decreased levels of Beclin-1, LC3A, and LC3B, which in turn decreased HgCl₂-induced autophagy damage. After HgCl₂ treatment, higher pathological damage was observed in terms of alveolar septal thickening, congestion, edema, and inflammatory cell infiltration compared to the control group while CRV ameliorated these effects. Consequently, by preventing HgCl₂-induced increases in oxidative stress and the corresponding inflammation, autophagy, apoptosis, and disturbance of tissue integrity in lung tissues, CRV might be seen as a useful therapeutic alternative.</p>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"39 12","pages":"5227-5237"},"PeriodicalIF":4.4,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/tox.24397","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Luteolin Inhibits Indoxyl Sulfate-Induced ICAM-1 and MCP-1 Expression by Inducing HO-1 Expression in EA.hy926 Human Endothelial Cells","authors":"Li-Chien Chang,&nbsp;En-Ling Yeh,&nbsp;Ya-Chi Chuang,&nbsp;Chia-Hsuan Wu,&nbsp;Chia-Wen Kuo,&nbsp;Chong-Kuei Lii,&nbsp;Ya-Chen Yang,&nbsp;Haw-Wen Chen,&nbsp;Chien-Chun Li","doi":"10.1002/tox.24380","DOIUrl":"10.1002/tox.24380","url":null,"abstract":"<div>\u0000 \u0000 <p>In patients with chronic kidney disease, the uremic toxin indoxyl sulfate (IS) accelerates kidney damage and the progression of cardiovascular disease. IS may contribute to vascular diseases by inducing inflammation in endothelial cells. Luteolin has documented antioxidant and anti-inflammatory properties. This study aimed to investigate the effect of luteolin on IS-mediated reactive oxygen species (ROS) production and intercellular adhesion molecule (ICAM-1) and monocyte chemoattractant protein (MCP-1) expression in EA.hy926 cells and the possible mechanisms involved. IS significantly induced ROS production (by 6.03-fold, <i>p</i> &lt; 0.05), ICAM-1 (by 2.19-fold, <i>p</i> &lt; 0.05) and MCP-1 protein expression (by 2.18-fold, <i>p</i> &lt; 0.05), and HL-60 cell adhesion (by 31%, <i>p</i> &lt; 0.05), whereas, luteolin significantly decreased IS-induced ROS production, ICAM-1 and MCP-1 protein expression, and HL-60 cell adhesion. Moreover, luteolin attenuated IS-induced nuclear accumulation of p65 and c-jun. Luteolin dose-dependently increased heme oxygenase-1 (HO-1) expression and the maximum fold induction of HO-1 by luteolin was 3.68-fold (<i>p</i> &lt; 0.05), whereas, HO-1 knockdown abolished the suppression of ICAM-1 and MCP-1 expression by luteolin. Luteolin may protect against IS-induced vessel damage by inducing HO-1 expression in vascular endothelial cells, which suppresses nuclear factor kappa B (NF-κB) and activator protein 1 (AP-1) mediated ICAM-1 and MCP-1 expression.</p>\u0000 </div>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"39 11","pages":"5112-5123"},"PeriodicalIF":4.4,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ameliorating and Therapeutic Impact of Curcumin Nanoparticles Against Aluminum Oxide Nanoparticles Induced Kidney Toxicity, DNA Damage, Oxidative Stress, PCNA and TNFα Alteration in Male Rats","authors":"Ehab Tousson,&nbsp;Ibrahim E. T. El-Sayed,&nbsp;Hebatalla Nashaat Elsharkawy,&nbsp;Amira S. Ahmed","doi":"10.1002/tox.24392","DOIUrl":"10.1002/tox.24392","url":null,"abstract":"<div>\u0000 \u0000 <p>Aluminum oxide nanoparticles (Al₂O₃ NPs) are among the most extensively utilized nanoparticles in nanotechnology and that have negative impacts on the environment. Therefore, the intention of this work is to investigate the protective and therapeutic effects of curcumin in nanoform <b>(</b>Cur NPs) against Al₂O₃ NPs induced kidney toxicity, oxidative stress, DNA damage, and changes in necrosis factor alpha (TNFα) and proliferating cell nuclear antigen (PCNA) expressions in male rats. Fifty healthy adult male were divided into five groups [G1, control; G2, received 50 mg/kg/day for 4 weeks of Cur NPs orally; G3, received 6 mg/kg BW orally for 4 weeks of Al₂O₃ NPs; G4, (Cur NPs + Al₂O₃ NPs) received Cur NPs and Al₂O₃ NPs at a dose similar to G2 and G3, respectively for 4 weeks; G5, (Al₂O₃ NPs + Cur NPs) received Al₂O₃ NPs at a dose similar to G3 for 4 weeks then received Cur NPs at a dose similar to G2 for another 4 weeks]. Current results revealed that Al₂O₃ NPs induced a significant elevation in serum urea, creatinine, chloride, calcium, kidney malondialdehyde (MDA), DNA damage, injury, TNFα and PCNA expressions and a significant depletion in serum potassium, kidney superoxide dismutase (SOD), glutathione (GSH) as compared to control. On the other hand, treatments of Al₂O₃ NPs with Cur NPs induced modulation in all altered parameters and improved kidney functions and structure, with best results for the Al₂O₃ NPs + Cur NPs than Cur NPs + Al₂O₃ NPs. In conclusion, Cur NPs has the capacity to mitigate the renal toxicity induced by Al₂O₃ NPs in male albino rats.</p>\u0000 </div>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"39 11","pages":"5140-5149"},"PeriodicalIF":4.4,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Naringenin Against Cadmium Toxicity in Fibroblast Cells: An Integrated Network Pharmacology and In Vitro Metabolomics Approach","authors":"Komal Priya,&nbsp;Ashim Chandra Roy,&nbsp;Abhinav Prasad,&nbsp;Prabhat Kumar,&nbsp;Ilora Ghosh","doi":"10.1002/tox.24388","DOIUrl":"10.1002/tox.24388","url":null,"abstract":"<div>\u0000 \u0000 <p>Cadmium, a heavy metal, disrupts cellular homeostasis and is highly toxic, with no effective treatments currently available against its toxicity. According to studies, phytochemicals provide a promising strategy for mitigating cadmium toxicity. Naringenin (NG), a potent antioxidant found primarily in citrus fruits, showed protective properties against cadmium toxicity in rats. Nonetheless, the precise mechanism of cadmium cytotoxicity in fibroblasts remains unknown. This study evaluated NG against cadmium (CdCl₂) toxicity utilizing network pharmacology and in silico molecular docking, and was further validated experimentally in rat fibroblast F111 cells. Using network pharmacology, 25 possible targets, including the top 10 targets of NG against cadmium, were identified. Molecular docking of interleukin 6 (IL6), the top potential target with NG, showed robust binding with an inhibition constant (Ki) of 58.76 μM, supporting its potential therapeutic potential. Pathway enrichment analysis suggested that “response to reactive oxygen species” and “negative regulation of small molecules metabolic process” were the topmost pathways targeted by NG against cadmium. In vitro analysis showed that NG (10 μM) attenuated CdCl₂-induced oxidative stress by reducing altered intracellular ROS, mitochondrial mass, and membrane potential. Also, NG reversed CdCl₂-mediated nuclear damage, G2/M phase arrest, and apoptosis. GC/MS-based metabolomics of F111 cells revealed CdCl₂ reduced cholesterol levels, which led to alterations in primary bile acid, steroid and steroid hormone biosynthesis pathways, whereas, NG restored these alterations. In summary, combined in silico and in vitro analysis suggested that NG protected cells from CdCl₂ toxicity by mitigating oxidative stress and metabolic pathway alterations, providing a comprehensive understanding of its protective mechanisms against cadmium-induced toxicity.</p>\u0000 </div>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"39 11","pages":"5124-5139"},"PeriodicalIF":4.4,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective Effects of Syringic Acid Against Oxidative Damage, Apoptosis, Autophagy, Inflammation, Testicular Histopathologic Disorders, and Impaired Sperm Quality in the Testicular Tissue of Rats Induced by Mercuric Chloride","authors":"Serkan Ali Akarsu,&nbsp;Cihan Gür,&nbsp;Sefa Küçükler,&nbsp;Nurhan Akaras,&nbsp;Mustafa İleritürk,&nbsp;Fatih Mehmet Kandemir","doi":"10.1002/tox.24395","DOIUrl":"10.1002/tox.24395","url":null,"abstract":"<p>Mercury (Hg) is one of the most toxic heavy metals that damage testicular tissue. Mercury chloride (HgCl₂) is one of the most toxic forms of mercury that can easily cross biological membranes. Syringic acid (SA) is a natural flavonoid found in many vegetables and fruits. In this study, the effects of SA against HgCl₂-induced testicular damage in rats were determined by biochemical, histopathological, and spermatological analyses. For this study, a total of 35 Spraque Dawley rats were used. Rats were divided into five groups as control, HgCl₂, SA 50, HgCl₂ + SA 25, and HgCl₂ + SA 50. HgCl₂ was administered intraperitoneal (IP) at a dose of 1.23 mg/kg/bw, while SA was administered by oral gavage at doses of 25 and 50 mg/kg/bw. The rats were then sacrificed, and testicular tissues were removed. HgCl₂ caused an increase in MDA level and a decrease in SOD, CAT, and GPx activity and GSH level in the testicular tissue of rats. HgCl₂ is involved in the increase of eIF2-α, PERK, ATF-4, ATF-6, CHOP, NF-κB, TNF-α, IL-1β, Apaf-1, Bax, and Caspase-3 mRNA expression. HgCl₂ caused a decrease in sperm motility, an increase in the rate of abnormal sperm and sperm DNA fragmentation in rats. However, SA oral administration dose-dependently inhibited endoplasmic reticulum stress, oxidative stress, inflammation, and apoptosis and preserved epididymal sperm quality and testicular histoarchitectures. In conclusion, SA had protective effects against HgCl₂-induced testicular oxidative damage, inflammation, endoplasmic reticulum stress, and apoptosis.</p>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"39 10","pages":"4803-4814"},"PeriodicalIF":4.4,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/tox.24395","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141878520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute Neurobehavioral and Glial Responses to Explosion Gas Inhalation in Rats","authors":"Jinren Liu,&nbsp;Junhong Gao,&nbsp;Hong Wang,&nbsp;Xiaolin Fan,&nbsp;Liang Li,&nbsp;Xiangni Wang,&nbsp;Xiying Wang,&nbsp;Jiajia Lu,&nbsp;Xingmin Shi,&nbsp;Pinglin Yang","doi":"10.1002/tox.24389","DOIUrl":"10.1002/tox.24389","url":null,"abstract":"<div>\u0000 \u0000 <p>Military personnel, firefighters, and fire survivors exhibit a higher prevalence of mental health conditions such as depression and post-traumatic stress disorder (PTSD) compared to the general population. While numerous studies have examined the neurological impacts of physical trauma and psychological stress, research on acute neurobehavioral effects of gas inhalation from explosions or fires is limited. This study investigates the early-stage neurobehavioral and neuronal consequences of acute explosion gas inhalation in Sprague–Dawley rats. Rats were exposed to simulated explosive gas and subsequently assessed using behavioral tests and neurobiological analyses. The high-dose exposure group demonstrated significant depression-like behaviors, including reduced mobility and exploration. However, neuronal damage was not evident in histological analyses. Immunofluorescence revealed increased density of radial glia and oligodendrocytes in specific brain regions, suggesting hypoxia and axon damage induced by gas inhalation as a potential mechanism for the observed neurobehavioral changes. These findings underscore the acute impact of explosion gas inhalation on mental health, highlighting the habenula and dentate gyrus of hippocampus as the possible target regions. The findings are expected to support early diagnosis and treatment strategies for brain injuries caused by explosion gas, offering insights into early intervention for depression and PTSD in affected populations.</p>\u0000 </div>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"39 11","pages":"5099-5111"},"PeriodicalIF":4.4,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polystyrene Microplastics Induce Injury to the Vascular Endothelial Through NLRP3-Mediated Pyroptosis","authors":"Chuanyi Huo,&nbsp;Ying Zhu,&nbsp;Xiaoqi Fang,&nbsp;Jianwei Cui,&nbsp;Hui Ye,&nbsp;Haotang Zhao,&nbsp;Lin Ye,&nbsp;Liting Zhou","doi":"10.1002/tox.24387","DOIUrl":"10.1002/tox.24387","url":null,"abstract":"<div>\u0000 \u0000 <p>The health risks associated with microplastics have attracted widespread attention. Polystyrene microplastics (PS-MPs) can induce damage to cardiac tissue, while pyroptosis-mediated injury to the vascular endothelial plays a vital role in the pathogenesis of cardiovascular diseases. The study intended to explore the role and mechanism of NLR family pyrin domain containing 3 (NLRP3) mediated pyroptosis in PS-MPs causing the injury of vascular endothelial cells. In vivo, Wistar rats were exposed to 0.5, 5, and 50 mg/kg/d 0.5 μm PS-MPs. In vitro, the human vascular endothelial cells (HUVECs) were used for mechanistic studies. siRNA was used for silencing the NILRP3 gene. H&amp;E staining and flow cytometry were performed to examine the vascular injury and cell membrane damage. The oxidative stress was detected by flow cytometry, immunofluorescence, and corresponding kits. ELISA were used to measure the levels of inflammatory factors. Real-time PCR and western blot were used to measure the expression of pyroptosis signaling pathway. In rats, PS-MPs could cause vascular damage, oxidative stress, and inflammatory response, and activated the pyroptosis signaling pathway. HUVECs exposure to PS-MPs, the vitality decreased in a dose-dependent manner, ROS and MDA were significantly increased while SOD was decreased. PS-MPs induced the onset of pyroptosis signaling pathway in HUVECs. Cell membrane damage and the levels of IL-Iβ and IL-18 in HUVECs significantly increased, those are symbols for the development of pyroptosis. Inhibition of NLRP3-mediated pyroptosis effectively protected HUVECs from PS-MPs-induced damage. Pyroptosis played a vital role in controlling the vascular endothelial injury caused by PS-MPs.</p>\u0000 </div>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"39 11","pages":"5086-5098"},"PeriodicalIF":4.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}