Toxicology最新文献

{"title":"HMGA2-mediated glutamine metabolism is required for Cd-induced cell growth and cell migration","authors":"Yanqiu Yang ,&nbsp;Chunpeng Gao ,&nbsp;Qiujuan Li ,&nbsp;Yong Liu ,&nbsp;Jun Cao","doi":"10.1016/j.tox.2024.153899","DOIUrl":"10.1016/j.tox.2024.153899","url":null,"abstract":"<div><p>Cadmium (Cd) exposure significantly increases the risk of lung cancer. The demand for glutamine is increasing in cancers, including lung cancer. In this study, we investigated the role of glutamine metabolism in Cd-induced cell growth and migration. Firstly, we found that 2 μM Cd-treatment up-regulated the expression of ASCT2 (alanine, serine, cysteine-preferring transporter 2) and ASNS (asparagine synthetase) while downregulating mitochondrial glutaminase GLS1 in A549 cells. The same results were obtained in male BALB/c mice treated with 0.5 and 1 mg Cd/kg body weight. Subsequently, both glutamine deprivation and transfection with siASCT2 revealed that glutamine played a role in Cd-induced cell growth and migration. Furthermore, using 4-PBA (5 mM), an inhibitor of endoplasmic reticulum (ER) stress, Tm (0.1 μg/ml), an inducer of ER stress, siHMGA2, and over-expressing HMGA2 plasmids we demonstrated that ER stress/HMGA2 axis was involved in inducing ASCT2 and ASNS, while inhibiting GLS1. Additionally, the chromatin immunoprecipitation assay using an HMGA2 antibody revealed the direct binding of the HMGA2 to the promoter sequences of the <em>ASCT2</em>, <em>ASNS</em>, and <em>GLS1</em> genes. Finally, dual luciferase reporter assay determined that HMGA2 increased the transcription of <em>ASCT2</em> and <em>ASNS</em> while inhibiting the transcription of <em>GLS1</em>. Overall, we found that ER stress-induced HMGA2 controls glutamine metabolism by transcriptional regulation of <em>ASCT2</em>, <em>ASNS</em> and <em>GLS1</em> to accelerate cell growth and migration during exposure to Cd at low concentrations. This study innovatively revealed the mechanism of Cd-induced cell growth which offers a fresh perspective on preventing Cd toxicity through glutamine metabolism.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"507 ","pages":"Article 153899"},"PeriodicalIF":4.8,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141735051","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":"Bisphenol S (BPS) induces glioblastoma progression via regulation of EZH2-mediated PI3K/AKT/mTOR pathway in U87-MG cells","authors":"Moon Yi Ko ,&nbsp;Heejin Park ,&nbsp;Younhee Kim ,&nbsp;Euijun Min ,&nbsp;Sin-Woo Cha ,&nbsp;Byoung-Seok Lee ,&nbsp;Sung-Ae Hyun ,&nbsp;Minhan Ka","doi":"10.1016/j.tox.2024.153898","DOIUrl":"10.1016/j.tox.2024.153898","url":null,"abstract":"<div><p>Bisphenol S (BPS), an alternative to bisphenol A (BPA), exerts proliferative effects similar to those of BPA. BPS is a representative endocrine disruptor associated with cancer progression. However, the mechanisms underlying BPS-induced glioblastoma progression are not fully understood. To investigate the effects of BPS on glioblastoma, U-87 MG cancer cell lines were exposed to BPS. The study focused on analyzing the proliferation and migration of U-87 MG cells. Furthermore, the involvement of the enhancer of the zeste homolog 2 (EZH2)-mediated phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of the rapamycin (mTOR) pathway was examined. Pharmacological approaches were employed to inhibit EZH2 activity and observe its effects on BPS-induced changes. The results indicated that BPS promoted the proliferation and migration of U-87 MG cells at a concentration of 0.1<!--> <!-->µM. These changes appeared to be linked to the activation of the EZH2-mediated PI3K/AKT/mTOR pathway. Moreover, inhibiting EZH2 activity using pharmacological approaches restored the BPS-mediated induction of proliferation and migration. In conclusion, the results of this study indicated that BPS induces glioblastoma progression through EZH2 upregulation. Therefore, targeting the EZH2-mediated PI3K/AKT/mTOR pathway could be considered a potential therapeutic strategy for the treatment of glioblastoma.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"507 ","pages":"Article 153898"},"PeriodicalIF":4.8,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0300483X24001793/pdfft?md5=5021c605b4163bf7c2440054d1efdedb&pid=1-s2.0-S0300483X24001793-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141732059","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":"Targeting SIRT1/AMPK/Nrf2/NF-кB by sitagliptin protects against oxidative stress-mediated ER stress and inflammation during ANIT-induced cholestatic liver injury","authors":"Rami M. Mosaoa ,&nbsp;Mohammed W. Al-Rabia ,&nbsp;Hani Z. Asfour ,&nbsp;Nabil A. Alhakamy ,&nbsp;Rasha A. Mansouri ,&nbsp;Dina S. El-Agamy ,&nbsp;Wesam H. Abdulaal ,&nbsp;Gamal A. Mohamed ,&nbsp;Sabrin R.M. Ibrahim ,&nbsp;Mahmoud Elshal","doi":"10.1016/j.tox.2024.153889","DOIUrl":"10.1016/j.tox.2024.153889","url":null,"abstract":"<div><p>Intrahepatic cholestasis is a common clinical form of hepatobiliary injury characterized by the intrahepatic accumulation of toxic bile acids. Besides its antidiabetic activity, the dipeptidyl peptidase IV inhibitor sitagliptin (SG) has been recently assigned diverse pharmacological activities and therapeutic potential against different disorders owing to its emerging antioxidant and anti-inflammatory properties. The current study explored the potential hepatoprotective effect of SG on α-naphthyl isothiocyanate (ANIT)-induced cholestatic liver injury (CLI) in mice and investigate its possible targeted signaling pathways. Mice received SG (10 and 20 mg/kg) for four consecutive days, two days before and after a single oral administration of ANIT (75 mg/kg). Our results revealed that SG administration remarkably prevented ANIT-induced histopathological lesions in the liver and maintained hepatic functions and oxidative/antioxidant balance. Ultimately, SG counteracted the inflammatory response in the liver, as indicated by the marked suppression of hepatic expression of NF-κB, TNF-α, and IL-6. Moreover, it inhibited the endoplasmic reticulum (ER) stress response in the liver. These beneficial effects of SG were accompanied by upregulation of SIRT1, p-AMPK, and Nrf2 expressions while downregulating keap1 expression in the liver. In conclusion, this study is the first to demonstrate the ability of SG to protect against ANIT-induced CLI through modulating multiple signaling cascades, including SIRT1/AMPK, Nrf2/keap1, and NF-кB, which resulted in enhanced antioxidant capacity and repressed inflammatory and ER stress responses in the liver.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"507 ","pages":"Article 153889"},"PeriodicalIF":4.8,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727887","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":"How does organophosphorus chemical warfare agent exposure affect respiratory physiology in mice?","authors":"Marilène Trancart,&nbsp;Antoine Botta,&nbsp;Christine Le Coz,&nbsp;Nathalie Guatto,&nbsp;André-Guilhem Calas,&nbsp;Anne-Sophie Hanak","doi":"10.1016/j.tox.2024.153890","DOIUrl":"10.1016/j.tox.2024.153890","url":null,"abstract":"<div><p>In the absence of appropriate medical care, exposure to organophosphorus nerve agents, such as VX, can lead to respiratory failure, and potentially death by asphyxiation. Despite the critical role of respiratory disturbances in organophosphorus-induced toxicity, the nature and underlying mechanisms of respiratory failure remain poorly understood. This study aimed to characterize respiratory alterations by determining their type and duration in mice exposed to a subcutaneous sublethal dose of VX. Respiratory ventilation in Swiss mice was monitored using dual-chamber plethysmography for up to 7 days post-exposure. Cholinesterase activity was assessed <em>via</em> spectrophotometry, and levels of inflammatory biomarkers were quantified using Luminex technology in blood and tissues involved in respiration (diaphragm, lung, and medulla oblongata). Additionally, a histological study was conducted on these tissues to ensure their structural integrity. Ventilatory alterations appeared 20–25 minutes after the injection of 0.9 LD₅₀ VX and increased until the end of the recording, i.e., 40 minutes after intoxication. Concurrent with the occurrence of apnea, increased inspiratory and expiratory times resulted in a significant decrease in respiratory rate in exposed mice compared to controls. Ventilatory amplitude and, consequently, minute volume were reduced, while specific airway resistance significantly increased, indicating bronchoconstriction. These ventilatory effects persisted up to 24 or even 72 hours post-intoxication, resolving on the 7th day. They were correlated with a decrease in acetylcholinesterase activity in the diaphragm, which persisted for up to 72 hours, and with the triggering of an inflammatory reaction in the same tissue. No significant histologic lesions were observed in the examined tissues. The ventilatory alterations observed up to 72 hours post-VX exposure appear to result from a functional failure of the respiratory system rather than tissue damage. This comprehensive characterization contributes to a better understanding of the respiratory effects induced by VX exposure, which is crucial for developing specific medical countermeasures.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"507 ","pages":"Article 153890"},"PeriodicalIF":4.8,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0300483X24001719/pdfft?md5=9e2e30ecfe86c38e52d7edd77ebec7a4&pid=1-s2.0-S0300483X24001719-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727886","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":"Methylglyoxal-derived hydroimidazolone-1/RAGE axis induces renal oxidative stress and renal fibrosis in vitro and in vivo","authors":"Gyuri Kim,&nbsp;Hee Joon Yoo,&nbsp;Min Ki Yoo,&nbsp;Ju Hyeong Choi,&nbsp;Kwang-Won Lee","doi":"10.1016/j.tox.2024.153887","DOIUrl":"10.1016/j.tox.2024.153887","url":null,"abstract":"<div><p>Advanced glycation end products (AGEs) are important contributors to the progression of chronic kidney diseases (CKD), including renal fibrosis. Although the relationship between AGEs and renal fibrosis has been well studied, the mechanisms of individual AGE-induced renal injury remain poorly understood. This study investigated the adverse effect of methylglyoxal-derived hydroimidazolone-1 (MG-H1), a methylglyoxal (MG)-derived AGE generated by the glycation of MG and arginine residues, on kidney damage. We aimed to elucidate the molecular mechanisms of MG-H1-mediated renal injury and fibrosis, focusing on the receptor for AGEs (RAGE) signaling and its effects on the Wnt/β-catenin pathway, MAPK pathway, and inflammatory responses. Our results suggest that the MG-H1/RAGE axis plays a significant role in the pathogenesis of CKD and its downstream events involving MAPK kinase-related factors and inflammatory factors. MG-H1 treatment modulated the expression of inflammatory cytokines (TNF-α, IL-6, and IL-1β) and MAPK proteins (ERK1/2, JNK, and p38).</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"507 ","pages":"Article 153887"},"PeriodicalIF":4.8,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141634618","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":"Study on the mechanisms of defective spermatogenesis induced by TiO2 NPs based on 3D blood−testis barrier microfluidic chip","authors":"Ruoyun Dong ,&nbsp;Li Li ,&nbsp;Hongmei Chang ,&nbsp;Guanling Song ,&nbsp;Sixiu Liu","doi":"10.1016/j.tox.2024.153888","DOIUrl":"10.1016/j.tox.2024.153888","url":null,"abstract":"<div><p>Titanium dioxide nanoparticles (TiO₂ NPs) can reduce sperm number, but the mechanisms of defective spermatogenesis induced by TiO₂ NPs have not been studied through cell-cell interactions at present. A kind of biomimetic three-dimensional blood−testis barrier microfluidic chip capable of intercellular communication was constructed with soft lithography techniques, including Sertoli cell (TM4), spermatogonia (GC-1) and vascular endothelial cell units, to study the mechanisms of TiO₂ NPs-induced defective spermatogenesis. TM4 and GC-1 cells cultured in TiO₂ NPs exposure and control chips were collected for transcriptomics and metabonomics analysis, and key proteins and metabolites in changed biological processes were validated. In TM4 cells, TiO₂ NPs suppressed glucose metabolism, especially lactate production, which reduced energy substrate supply for spermatogenesis. TiO₂ NPs also decreased the levels of key proteins and metabolites of lactate production. In GC-1 cells, TiO₂ NPs disturbed chemokine signaling pathways regulating cell proliferation and interfered with glutathione metabolism. The Cxcl13, Stat3 and p-Stat3 levels and cell proliferation rate were decreased, and the GSR, GPX4 and GSH contents were increased in GC-1 cells in chips under TiO₂ NPs treatment. The decrease in energy substrate supply for spermatogenesis and inhibition of spermatogonia proliferation could be the main mechanisms of defective spermatogenesis induced by TiO₂ NPs.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"507 ","pages":"Article 153888"},"PeriodicalIF":4.8,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141634619","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":"Investigation of cannabidiol-induced cytotoxicity in human hepatic cells","authors":"Si Chen ,&nbsp;Xilin Li ,&nbsp;Qiangen Wu ,&nbsp;Yuxi Li ,&nbsp;Montserrat Puig ,&nbsp;Frederic Moulin ,&nbsp;Supratim Choudhuri ,&nbsp;Jeremy Gingrich ,&nbsp;Lei Guo","doi":"10.1016/j.tox.2024.153884","DOIUrl":"10.1016/j.tox.2024.153884","url":null,"abstract":"<div><p>Cannabidiol (CBD) is one of the primary cannabinoids present in extracts of the plant <em>Cannabis sativa L</em>. A CBD-based drug, Epidiolex, has been approved by the U.S. FDA for the treatment of seizures in childhood-onset epileptic disorders. Although CBD-associated liver toxicity has been reported in clinical studies, the underlying mechanisms remain unclear. In this study, we demonstrated that CBD causes cytotoxicity in primary human hepatocytes and hepatic HepG2 cells. A 24-h CBD treatment induced cell cycle disturbances, cellular apoptosis, and endoplasmic reticulum (ER) stress in HepG2 cells. A potent ER stress inhibitor, 4-phenylbutyrate, markedly attenuated CBD-induced apoptosis and cell death. Additionally, we investigated the role of cytochrome P450 (CYP)-mediated metabolism in CBD-induced cytotoxicity using HepG2 cell lines engineered to express 14 individual CYPs. We identified CYP2C9, 2C19, 2D6, 2C18, and 3A5 as participants in CBD metabolism. Notably, cells overexpressing CYP2C9, 2C19, and 2C18 produced 7-hydroxy-CBD, while cells overexpressing CYP2C9, 2C19, 2D6, and 2C18 generated 7-carboxy-CBD. Furthermore, CBD-induced cytotoxicity was significantly attenuated in the cells expressing CYP2D6. Taken together, these data suggest that cell cycle disturbances, apoptosis, and ER stress are associated with CBD-induced cytotoxicity, and CYP2D6-mediated metabolism plays a critical role in decreasing the cytotoxicity of CBD.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"506 ","pages":"Article 153884"},"PeriodicalIF":4.8,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617095","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":"Benzo(a)pyrene promotes the malignant progression of malignant-transformed BEAS-2B cells by regulating YTH N6-methyladenosine RNA binding protein 1 to inhibit ferroptosis","authors":"Na Wang ,&nbsp;Hong-qiang Chen ,&nbsp;Yong Zeng ,&nbsp;Yu Shi ,&nbsp;Zhe Zhang ,&nbsp;Jiang-ying Li ,&nbsp;Shi-meng Zhou ,&nbsp;Ya-wen Li ,&nbsp;Shuang-wu Deng ,&nbsp;Xue Han ,&nbsp;Zi-yuan Zhou ,&nbsp;Mao-lin Yao ,&nbsp;Wen-bin Liu","doi":"10.1016/j.tox.2024.153886","DOIUrl":"10.1016/j.tox.2024.153886","url":null,"abstract":"<div><p>Benzo[<em>a</em>]pyrene (BaP) is associated with the development of lung cancer, but the underlying mechanism has not been completely clarified. Here, we used 10 μM BaP to induce malignant transformation of human bronchial epithelial BEAS-2B cells, named BEAS-2B-T. Results indicated that BaP (6.25, 12.5 and 25 μM) treatment significantly promoted the migration and invasion of BEAS-2B-T cells. Meanwhile, BaP exposure inhibited ferroptosis in BEAS-2B-T, ferroptosis-related indexes Fe²⁺, malondialdehyde (MDA), lipid peroxidation (LPO) and reactive oxygen species (ROS) decreased significantly. The protein level of ferroptosis-related molecule transferrin receptor (TFRC) decreased significantly, while solute carrier family 7 membrane 11 (SLC7A11), ferritin heavy chain 1 (FTH1) and glutathione peroxidase 4 (GPX4) increased significantly. The intervention of ferroptosis dramatically effected the migration and invasion of BEAS-2B-T induced by BaP. Furthermore, the expression of YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) was markedly increased after BaP exposure. YTHDF1 knockdown inhibited BEAS-2B-T migration and invasion by promoting ferroptosis. In the meantime, the contents of Fe²⁺, MDA, LPO and ROS increased significantly, TFRC was markedly increased, and SLC7A11, FTH1, and GPX4 were markedly decreased. Moreover, overexpression of YTHDF1 promoted BEAS-2B-T migration and invasion by inhibiting ferroptosis. Importantly, knockdown of YTHDF1 promoted ferroptosis and reduced BEAS-2B-T migration and invasion during BaP exposure, and overexpression of YTHDF1 increased migration and invasion of BEAS-2B-T by inhibiting ferroptosis during BaP exposure. RNA immunoprecipitation assays indicated that the binding of YTHDF1 to SLC7A11 and FTH1 markedly increased after YTHDF1 overexpression. Therefore, we concluded that BaP promotes the malignant progression of BEAS-2B-T cells through YTHDF1 upregulating SLC7A11 and FTH1 to inhibit ferroptosis. This study reveals new epigenetic and ferroptosis markers for preventing and treating lung cancer induced by environmental carcinogens.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"507 ","pages":"Article 153886"},"PeriodicalIF":4.8,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141604142","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":"Comparison on the mechanism and potency of hepatotoxicity among hemp extract and its four major constituent cannabinoids","authors":"Xiugong Gao,&nbsp;Kayla Campasino,&nbsp;Miranda R. Yourick,&nbsp;Yang Zhao,&nbsp;Estatira Sepehr,&nbsp;Cory Vaught,&nbsp;Robert L. Sprando,&nbsp;Jeffrey J. Yourick","doi":"10.1016/j.tox.2024.153885","DOIUrl":"10.1016/j.tox.2024.153885","url":null,"abstract":"<div><p>Cannabidiol (CBD) has been reported to induce hepatotoxicity in clinical trials and research studies; however, little is known about the safety of other nonintoxicating cannabinoids. New approach methodologies (NAMs) based on bioinformatic analysis of high-throughput transcriptomic data are gaining increasing importance in risk assessment and regulatory decision-making of data-poor chemicals. In the current study, we conducted a concentration response transcriptomic analysis of hemp extract and its four major constituent cannabinoids [CBD, cannabichromene (CBC), cannabigerol (CBG), and cannabinol (CBN)] in hepatocytes derived from human induced pluripotent stem cells (iPSCs). Each compound impacted a distinctive combination of biological functions and pathways. However, all the cannabinoids impaired liver metabolism and caused oxidative stress in the cells. Benchmark concentration (BMC) analysis showed potencies in transcriptional activity of the cannabinoids were in the order of CBN &gt; CBD &gt; CBC &gt; CBG, consistent with the order of their cytotoxicity IC₅₀ values. Patterns of transcriptomic changes induced by hemp extract and its median overall BMC were very similar to CBD but differed significantly from other cannabinoids, suggesting that potential adverse effects of hemp extract were largely due to its major constituent CBD. Lastly, transcriptomic point-of-departure (tPoD) values were determined for each of the compounds, with the value for CBD (0.106 µM) being concordant with a previously reported one derived from apical endpoints of clinical and animal studies. Taken together, the current study demonstrates the potential utility of transcriptomic BMC analysis as a NAM for hazard assessment of data-poor chemicals, improves our understanding of the possible health effects of hemp extract and its constituent cannabinoids, and provides important tPoD data that could contribute to inform human safety assessment of these cannabinoid compounds.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"506 ","pages":"Article 153885"},"PeriodicalIF":4.8,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0300483X24001665/pdfft?md5=5269da056073688739f24952d7304052&pid=1-s2.0-S0300483X24001665-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617094","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":"Developments in the field of intestinal toxicity and signaling pathways associated with rodent exposure to micro(nano)plastics","authors":"","doi":"10.1016/j.tox.2024.153883","DOIUrl":"10.1016/j.tox.2024.153883","url":null,"abstract":"<div><p>The broad spread of micro(nano)plastics (MNPs) has garnered significant attention in recent years. MNPs have been detected in numerous human organs, indicating that they may also be hazardous to humans. The toxic effects of MNPs have been demonstrated in marine species and experimental animals. The primary pathway and target organ for MNPs entering the human body is the intestinal system, and increasing research has been done on the harmful effects and subsequent mechanisms of exposure to MNPs. Studies on how MNPs affect gut health in humans are scarce, nevertheless. Since rodents are frequently employed as animal models for human ailments, research on rodents exposed to MNPs can provide a more accurate representation of human circumstances. This study examined the effects of MNPs on intestinal microecology, inflammation, barrier function, and ion transport channels in rodents. It also reviewed the signal pathways involved, such as oxidative stress, nuclear factor (NF)-κB, Toll-like receptor (TLR) 4, inflammatory corpuscles, muscarinic acetylcholine receptors (mAChRs), mitogen-activated protein kinase (MAPK), and cell death. This review will offer a conceptual framework for the management and avoidance of associated illnesses.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"507 ","pages":"Article 153883"},"PeriodicalIF":4.8,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141601800","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}