Toxicology最新文献

{"title":"Fumonisin distorts the cellular membrane lipid profile: A mechanistic insight","authors":"Omeralfaroug Ali ,&nbsp;András Szabó","doi":"10.1016/j.tox.2024.153860","DOIUrl":"10.1016/j.tox.2024.153860","url":null,"abstract":"<div><p>Monitoring modifications in membrane lipids in association with external stimuli/agents, including fumonisins (FUMs), is a widely employed approach to assess cellular metabolic response/status. FUMs are prevalent fusariotoxins worldwide that have diverse structures with varying toxicity across species; nevertheless, they can induce metabolic disturbances and disease, including cancer. The capacity of FUMs to disrupt membrane lipids, demonstrated across numerous species and organs/tissues, is ascribed to a multitude of factors/events, which range from direct to indirect effects. Certain events are well established, whereas the potential consequences of others remain speculative. The most notable effect is their resemblance to sphingoid bases, which impacts the synthesis of ceramides leading to numerous changes in lipids’ composition that are not limited to sphingolipids’ composition of the membranes. The next plausible scenario involves the induction of oxidative stress, which is considered an indirect/secondary effect of FUMs. Additional modes of action include modifications of enzyme activities and nuclear signals related to lipid metabolism, although these are likely not yet fully comprehended. This review provides in-depth insight into the current state of these events and their potential mechanistic actions in modifying membrane lipids, with a focus on long-chain fatty acids. This paper also presents a detailed description of the reported modifications to membrane lipids by FUMs.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0300483X24001410/pdfft?md5=c5149234773aa108b1f5988d0dbdf9b7&pid=1-s2.0-S0300483X24001410-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141318365","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":"MLKL deficiency alleviates acute alcoholic liver injury via inhibition of NLRP3 inflammasome","authors":"Yue Shen ,&nbsp;Dongliang Chen ,&nbsp;Min Linghu ,&nbsp;Bo Huang ,&nbsp;Shangfu Xu ,&nbsp;Lisheng Li ,&nbsp;Yuanfu Lu ,&nbsp;Xia Li","doi":"10.1016/j.tox.2024.153864","DOIUrl":"https://doi.org/10.1016/j.tox.2024.153864","url":null,"abstract":"<div><p>Mixed lineage kinase domain-like protein (MLKL) is identified as the terminal executor of necroptosis. However, its role in acute alcoholic liver injury remains unclear. This study elucidates that MLKL can contribute to acute alcoholic liver injury independently of necroptosis. Although the expression of MLKL was upregulated, no significant increase in its phosphorylation or membrane translocation was observed in the liver tissues of mice treated with ethanol. This finding confirms that alcohol intake does not induce necroptosis in mouse liver tissue. Additionally, the deletion of <em>Mlkl</em> resulted in the downregulation of NLRP3 expression, which subsequently inhibited the activation of the NLRP3 inflammasome and the ensuing inflammatory response, thereby effectively mitigating liver injury induced by acute alcohol consumption. The knockout of <em>Nlrp3</em> did not affect the expression of MLKL, further confirming that MLKL acts upstream of NLRP3. Mechanistically, inhibiting the nuclear translocation of MLKL reduced the nuclear entry of p65, the principal transcriptional regulator of NLRP3, thereby limiting the transcription of <em>Nlrp3</em> mRNA and subsequent NLRP3 expression. Overall, this study unveils a novel mechanism of MLKL regulates the activation of NLRP3 inflammasomes in a necroptosis independent way in acute alcoholic liver injury</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0300483X24001458/pdfft?md5=bae15d082f23c65de737542a21019552&pid=1-s2.0-S0300483X24001458-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141314458","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":"Toxicity mechanism of acrolein on energy metabolism disorder and apoptosis in human ovarian granulosa cells","authors":"Xueping Liu ,&nbsp;Rongxia Li ,&nbsp;Zi Xiu ,&nbsp;Siling Tang ,&nbsp;Yancang Duan","doi":"10.1016/j.tox.2024.153861","DOIUrl":"https://doi.org/10.1016/j.tox.2024.153861","url":null,"abstract":"<div><p>Acrolein (ACR), an unsaturated, highly reactive aldehyde, is a widespread environmental toxin. ACR exerts permanent and irreversible side effects on ovarian functions. Granulosa cells play a crucial role in supporting ovarian function. Thus, in this study, we investigated the toxicity effects of granulosa cells induced by ACR. Following treatment with varying ACR concentrations (0, 12.5, 25, 50, and 100 μM), we observed that ACR exposure induced reactive oxygen species accumulation, mitochondrial energy metabolism disorder, and apoptosis in KGN cells (a human ovarian granulosa cell line) in a dose-dependent manner. In addition, mitochondrial biogenesis in KGN cells displayed biphasic changes after ACR exposure, with activation at a low ACR dose (12.5 μM), but inhibition at higher ACR doses (≥50 μM). SIRT1/PGC-1α-mediated mitochondrial biogenesis is crucial for maintaining intracellular mitochondrial homeostasis and cellular function. The inhibition/activation of the SIRT1/PGC-1α pathway in KGN cells validated its role in ACR-induced damage. The results indicated that the inhibition of the SIRT1/PGC-1α pathway aggravated ACR-induced cell damage, whereas its activation partially counteracted ACR-induced cell damage. This study attempted to uncover a novel mechanism of ACR-induced ovarian toxicity so as to provide an effective treatment option for safeguarding female reproductive health from the adverse effects of ACR.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0300483X24001422/pdfft?md5=c895ae7d80991c8338d35963faa1ff5e&pid=1-s2.0-S0300483X24001422-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141302747","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":"Legacy and alternative per- and polyfluoroalkyl substances (PFAS) alter the lipid profile of HepaRG cells","authors":"Lackson Kashobwe ,&nbsp;Faezeh Sadrabadi ,&nbsp;Lars Brunken ,&nbsp;Ana Carolina M.F. Coelho ,&nbsp;Torkjel M. Sandanger ,&nbsp;Albert Braeuning ,&nbsp;Thorsten Buhrke ,&nbsp;Mattias Öberg ,&nbsp;Timo Hamers ,&nbsp;Pim.E.G. Leonards","doi":"10.1016/j.tox.2024.153862","DOIUrl":"10.1016/j.tox.2024.153862","url":null,"abstract":"<div><p>Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals used in various industrial and consumer products. They have gained attention due to their ubiquitous occurrence in the environment and potential for adverse effects on human health, often linked to immune suppression, hepatotoxicity, and altered cholesterol metabolism. This study aimed to explore the impact of ten individual PFAS, 3 H-perfluoro-3-[(3-methoxypropoxy) propanoic acid] (PMPP/Adona), ammonium perfluoro-(2-methyl-3-oxahexanoate) (HFPO-DA/GenX), perfluorobutanoic acid (PFBA), perfluorobutanesulfonic acid (PFBS), perfluorodecanoic acid (PFDA), perfluorohexanoic acid (PFHxA), perfluorohexanesulfonate (PFHxS), perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), and perfluorooctanesulfonic acid (PFOS) on the lipid metabolism in human hepatocyte-like cells (HepaRG). These cells were exposed to different concentrations of PFAS ranging from 10 µM to 5000 µM. Lipids were extracted and analyzed using liquid chromatography coupled with mass spectrometry (LC- MS-QTOF). PFOS at 10 µM and PFOA at 25 µM increased the levels of ceramide (Cer), diacylglycerol (DAG), N-acylethanolamine (NAE), phosphatidylcholine (PC), and triacylglycerol (TAG) lipids, while PMPP/Adona, HFPO-DA/GenX, PFBA, PFBS, PFHxA, and PFHxS decreased the levels of these lipids. Furthermore, PFOA and PFOS markedly reduced the levels of palmitic acid (FA 16.0). The present study shows distinct concentration-dependent effects of PFAS on various lipid species, shedding light on the implications of PFAS for essential cellular functions. Our study revealed that the investigated legacy PFAS (PFOS, PFOA, PFBA, PFDA, PFHxA, PFHxS, and PFNA) and alternative PFAS (PMPP/Adona, HFPO-DA/GenX and PFBS) can potentially disrupt lipid homeostasis and metabolism in hepatic cells. This research offers a comprehensive insight into the impacts of legacy and alternative PFAS on lipid composition in HepaRG cells.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0300483X24001434/pdfft?md5=45399d231e3fa900b7450e7e6e3bb0ef&pid=1-s2.0-S0300483X24001434-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141311768","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":"Next generation risk assessment for occupational chemical safety – A real world example with sodium-2-hydroxyethane sulfonate","authors":"Adam Wood ,&nbsp;Catherine Breffa ,&nbsp;Caroline Chaine ,&nbsp;Richard Cubberley ,&nbsp;Matthew Dent ,&nbsp;Joachim Eichhorn ,&nbsp;Susann Fayyaz ,&nbsp;Fabian A. Grimm ,&nbsp;Jade Houghton ,&nbsp;Reiko Kiwamoto ,&nbsp;Predrag Kukic ,&nbsp;MoungSook Lee ,&nbsp;Sophie Malcomber ,&nbsp;Suzanne Martin ,&nbsp;Beate Nicol ,&nbsp;Joe Reynolds ,&nbsp;Gordon Riley ,&nbsp;Sharon Scott ,&nbsp;Colin Smith ,&nbsp;Carl Westmoreland ,&nbsp;Steve Gutsell","doi":"10.1016/j.tox.2024.153835","DOIUrl":"10.1016/j.tox.2024.153835","url":null,"abstract":"<div><p>Next Generation Risk Assessment (NGRA) is an exposure-led approach to safety assessment that uses New Approach Methodologies (NAMs). Application of NGRA has been largely restricted to assessments of consumer use of cosmetics and is not currently implemented in occupational safety assessments, e.g. under EU REACH. By contrast, a large proportion of regulatory worker safety assessments are underpinned by toxicological studies using experimental animals. Consequently, occupational safety assessment represents an area that would benefit from increasing application of NGRA to safety decision making. Here, a workflow for conducting NGRA under an occupational safety context was developed, which is illustrated with a case study chemical; sodium 2-hydroxyethane sulphonate (sodium isethionate or SI). Exposures were estimated using a standard occupational exposure model following a comprehensive life cycle assessment of SI and considering factory-specific data. Outputs of this model were then used to estimate internal exposures using a Physiologically Based Kinetic (PBK) model, which was constructed with SI specific Absorption, Distribution, Metabolism and Excretion (ADME) data. PBK modelling indicated a worst-case plasma maximum concentration (C_max) of 0.8 μM across the SI life cycle. SI bioactivity was assessed in a battery of NAMs relevant to systemic, reproductive, and developmental toxicity; a cell stress panel, high throughput transcriptomics in three cell lines (HepG2, HepaRG and MCF-7 cells), pharmacological profiling and specific assays relating to developmental toxicity (Reprotracker and devTOX quickPredict). Points of Departure (PoDs) for SI ranged from 104 to 5044 µM. C_max values obtained from PBK modelling of occupational exposures to SI were compared with PoDs from the bioactivity assays to derive Bioactivity Exposure Ratios (BERs) which demonstrated the safety for workers exposed to SI under current levels of factory specific risk management. In summary, the tiered and iterative workflow developed here represents an opportunity for integrating non animal approaches for a large subset of substances for which systemic worker safety assessment is required. Such an approach could be followed to ensure that animal testing is only conducted as a “last resort” e.g. under EU REACH.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0300483X24001161/pdfft?md5=585c1e95395770ef0aece7c2e480a9c5&pid=1-s2.0-S0300483X24001161-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141301618","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":"Analysis of environmental pollutant Bisphenol F elicited prostate injury targets and underlying mechanisms through network toxicology, molecular docking, and multi-level bioinformatics data integration","authors":"Shujun Huang","doi":"10.1016/j.tox.2024.153847","DOIUrl":"10.1016/j.tox.2024.153847","url":null,"abstract":"<div><p>Bisphenol F (BPF) has gained prominence as an alternative to bisphenol A (BPA) in various manufacturing applications, yet being detected in diverse environments and posed potential public health risk. This research aims to elucidate the putative toxic targets and underlying molecular mechanisms of prostate injury induced by exposure to BPF through multi-level bioinformatics data, integrating network toxicology and molecular docking. Systematically leveraging multilevel databases, we determined 276 targets related to BPF and prostate injury. Subsequent screenings through STRING and Cytoscape tool highlighted 27 key targets, including <em>BCL2</em>, <em>HSP90AA1</em>, <em>MAPK3</em>, <em>ESR1</em>, and <em>CASP3</em>. GO and KEGG enrichment analyses demonstrated enrichment of targets involved in apoptosis, abnormal hormonal activities, as well as cancer-related signal transduction cascades, ligand-receptor interaction networks, and endocrine system signaling pathways. Molecular docking simulations conducted via Autodock corroborated high-affinity binding interaction between BPF and key targets. The results indicate that BPF exposure can contribute to the initiation and progression of prostate cancer and prostatic hyperplastic by modulating apoptosis and proliferation, altering nerve function in blood vessel endothelial cells, and disrupting androgen metabolism. This study offers theoretical underpinnings for comprehending the molecular mechanisms implicated in BPF-elicited prostatic toxicity, while concomitantly establishing foundational framework for the development of prophylactic and therapeutic strategies for prostatic injuries related to polycarbonate and epoxy resin plastics incorporated with BPF, as well as environments afflicted by elevated levels of these compounds.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141237055","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":"Role of brain monoamines in acetamiprid-induced anxiety-like behavior","authors":"Anri Hirai ,&nbsp;Chitoku Toda ,&nbsp;Yared Beyene Yohannes ,&nbsp;Nimako Collins ,&nbsp;Mai Tamba ,&nbsp;Kei Nomiyama ,&nbsp;Akifumi Eguchi ,&nbsp;Nobuhiko Hoshi ,&nbsp;Tetsushi Hirano ,&nbsp;Shouta M.M. Nakayama ,&nbsp;Mayumi Ishizuka ,&nbsp;Yoshinori Ikenaka","doi":"10.1016/j.tox.2024.153839","DOIUrl":"10.1016/j.tox.2024.153839","url":null,"abstract":"<div><p>Neonicotinoid (NN) pesticides have been linked to increased brain dysfunction in mammals, such as anxiety-like behavior; this is thought to involve monoamines (MA), neurotransmitters that control behavior, memory, and learning. However, the mechanism by which NNs affect the central nervous system is not fully understood. In this study, we aimed to investigate whether MAs affect NNs-induced anxiety-like behavior. Mice were orally administered acetamiprid (ACE), an NN, at the no observed adverse effect level (NOAEL) of mouse (20 mg/kg body mass) set by the Food Safety Commission of Japan, and the elevated zero-maze (EZM) test was performed 30 min after administration. After behavioral analysis, levels of four MA (dopamine, 3-MT, serotonin, and histamine) in selected brain regions were determined by liquid chromatography mass spectrometry (LC/MS/MS). In the exposed group, a trend toward increased anxiety-like behavior was observed, and at least one MA concentration was significantly increased in each region. Further, significant correlations were found between behavioral test results and hippocampal serotonin and striatal dopamine concentrations, as well as between dopamine and serotonin concentrations, in the exposed group. As anxiety can influence activity in the behavioral tests, the activity of neurons in the raphe nuclei (RN), a brain region greatly involved in anxiety via the serotonergic system, was examined by staining with anti-serotonin antibodies, and increased serotonergic activity was observed. Taken together, these results suggest that ACE regulates MA levels, notably serotonin levels in the hippocampus and that RN plays an important role in ACE-induced anxiety-like behavior.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141088009","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":"Endocrine toxicity of atrazine and its underlying mechanisms","authors":"Haotang Zhao,&nbsp;Honghao Qian,&nbsp;Jianwei Cui,&nbsp;Zhili Ge ,&nbsp;Jingjing Shi,&nbsp;Yingchao Huo,&nbsp;Yuezhu Zhang,&nbsp;Lin Ye","doi":"10.1016/j.tox.2024.153846","DOIUrl":"10.1016/j.tox.2024.153846","url":null,"abstract":"<div><p>Atrazine (ATR) is one of the most widely utilized herbicides globally and is prevalent in the environment due to its extensive use and long half-life. It can infiltrate the human body through drinking water, ingestion, and dermal contact, and has been recognized as an environmental endocrine disruptor. This study aims to comprehensively outline the detrimental impacts of ATR on the endocrine system. Previous research indicates that ATR is harmful to various bodily systems, including the reproductive system, nervous system, adrenal glands, and thyroi d gland. The toxic effects of ATR on the endocrine system and its underlying molecular mechanisms are summarized as follows: influencing the expression of kisspeptin in the HPG axis, consequently affecting steroid synthesis; disrupting DNA synthesis and meiosis, as well as modifying DNA methylation levels, leading to reproductive and developmental toxicity; impacting dopamine by altering Nurr1, VMAT2, and DAT expression, consequently affecting dopamine synthesis and transporter expression, and influencing other neurotransmitters, resulting in neurotoxicity; and changing adipose tissue synthesis and metabolism by reducing basal metabolism, impairing cellular oxidative phosphorylation, and inducing insulin resistance. Additionally, a compilation of natural products used to mitigate the toxic effects of ATR has been provided, encompassing melatonin, curcumin, quercetin, lycopene, flavonoids, vitamin C, vitamin E, and other natural remedies. It is important to note that existing research predominantly relies on in vitro and ex vivo experiments, with limited population-based empirical evidence available.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141180748","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":"Ferroptosis is involved in cisplatin sensitivity of the S3 segment of immortalized proximal tubule cells","authors":"Hiroki Taguchi,&nbsp;Daigo Sumi,&nbsp;Seiichiro Himeno,&nbsp;Hitomi Fujishiro","doi":"10.1016/j.tox.2024.153840","DOIUrl":"10.1016/j.tox.2024.153840","url":null,"abstract":"<div><p>Cisplatin (CDDP) is administered as an anticancer drug across a broad spectrum of cancer treatments, but it causes severe renal damage. Several studies have attempted to elucidate the cause of CDDP-induced renal injury, but the detailed mechanism remains unclear. We previously found that S3 cells are more sensitive to CDDP than S1 and S2 cells by using immortalized cells derived from S1, S2, and S3 segments of proximal tubules. In this study, we investigated the potential contribution of reactive oxygen species (ROS) to the sensitivity of S3 cells to CDDP. The results showed that S3 cells have high sensitivity to CDDP, paraquat (PQ) and three ROS substances. To examine the mechanisms underlying the sensitivity to ROS in S3 cells, we compared the cellular responses of CDDP- and PQ-exposed S3 cells. The results indicated that the levels of intracellular ROS and lipid peroxides were increased in S3 cells after CDDP and PQ exposure. The intracellular levels of antioxidant proteins such as thioredoxin, thioredoxin reductase 1 and glutathione peroxidase 4 were also increased by exposure to PQ, but these proteins were decreased by CDDP exposure in S3 cells. Furthermore, the levels of intracellular free Fe²⁺ were increased by CDDP exposure only in S3 cells but not S1 or S2 cells, and cytotoxicity by exposure to CDDP in S3 cells was suppressed by ferroptosis inhibitors. These results suggested that the induction of ferroptosis due to the ROS production through attenuation of the antioxidant system and elevated free Fe²⁺ is partly responsible for the sensitivity of S3 cells to CDDP.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141237483","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":"A single and short exposure to heated tobacco vapor or cigarette smoke affects macrophage activation and polarization","authors":"Pablo Scharf ,&nbsp;Silvana Sandri ,&nbsp;Pâmela Pacassa Borges ,&nbsp;Tiago Franco de Oliveira ,&nbsp;Sandra Helena Poliselli Farsky","doi":"10.1016/j.tox.2024.153859","DOIUrl":"10.1016/j.tox.2024.153859","url":null,"abstract":"<div><p>The toxicity of heated tobacco products (HTP) on the immune cells remains unclear. Here, U937-differentiated macrophages were exposed to a single and short-term exposure (30 minutes) of HTP vapor or cigarette smoke (CS) in an air-liquid interface (ALI) system to evaluate the effects on macrophages' early activation and polarization. In our system, HTP released lower amounts of polycyclic aromatic hydrocarbons (PAHs), but higher nicotine levels than CS into the cell culture supernatant. Both tobacco products triggered the expression of the α-7 nicotinic receptor (α7 nAChR) and reactive oxygen species (ROS) production. When challenged with a bacterial product, lipopolysaccharide (LPS), cells exposed to HTP or CS failed to respond properly and enhance ROS production upon LPS stimuli. Furthermore, both tobacco products also impaired bacterial phagocytosis and the exposures triggered higher IL-1β secretion. The α7 nAChR antagonist treatment rescued the effects caused only by HTP exposure. The CS-exposed group switched macrophage to the pro-inflammatory M1, while HTP polarized to the suppressive M2 profile. Associated, data highlight that HTP and CS exposures similarly activate macrophages; nonetheless, the α7 nAChR pathway is only involved in HTP actions, and the distinct subsequent polarization caused by HTP or CS may influence the outcome of host defense.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141201703","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}