Toxicology最新文献

{"title":"T-2 toxin induces anemia via disrupting erythroid commitment and differentiation","authors":"Yan Li ,&nbsp;Jingxin Zhang ,&nbsp;Longzhen Zhao ,&nbsp;Peijun Jia ,&nbsp;Yazhe Zhen ,&nbsp;Huan Zhang ,&nbsp;Yuanlin Xu ,&nbsp;Shijie Zhang","doi":"10.1016/j.tox.2025.154126","DOIUrl":"10.1016/j.tox.2025.154126","url":null,"abstract":"<div><div>T-2 toxin, a stable and highly toxic secondary metabolite produced by <em>Fusarium</em>, is known to have strong cytotoxicity and threaten multiple systems. However, its effect on the hematopoietic system and the mechanisms of anemia induction remains unclear. Here, we establish the acute T-2 toxin poisoning mouse model at concentrations ranging between 0.5 and 4 mg/kg. Our results show that T-2 toxin exposure causes severe anemia in mice, as indicated by significant reductions in red blood cell count and hemoglobin levels. Further analysis indicates that T-2 toxin profoundly disrupts the homeostasis of hematopoietic stem cells and their commitment to the erythroid lineage and subsequent erythroid differentiation, thus significantly inhibiting the formation of erythroblasts and reticulocytes. In humans, cells are exposed to T-2 toxin at concentrations of 0.25–1 ng/mL for 13 days. T-2 toxin strongly inhibits erythropoiesis and promotes the formation of abnormal nucleated erythroblasts. Mechanistically, high concentration of T-2 toxin induces apoptosis, while lower levels arrest the cell cycle at the G1/S phase. Overall, our findings reveal the hematotoxic effects of T-2 toxin and shed light on the mechanisms underlying T-2 toxin induced anemia, providing valuable guidance for developing strategies to mitigate T-2 toxin poisoning.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"514 ","pages":"Article 154126"},"PeriodicalIF":4.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731721","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":"Identification of key genes linking bisphenols exposure and breast cancer","authors":"Zhen Wang ,&nbsp;Meng Cao ,&nbsp;Tian Gao ,&nbsp;Xinyue Xu ,&nbsp;Weihua Yu ,&nbsp;Jiangzheng Liu ,&nbsp;Rui Liu ,&nbsp;Xiaodi Zhang ,&nbsp;Fei Li ,&nbsp;Chunxu Hai","doi":"10.1016/j.tox.2025.154123","DOIUrl":"10.1016/j.tox.2025.154123","url":null,"abstract":"<div><div>Breast cancer (BC) is one of the most common types of cancer and is caused by the complex interplay of genetic and environmental factors, such as an unhealthy lifestyle, family history of illness, reproductive factors, and ageing. However, increasing evidence has revealed that manufactured organic pollutants such as bisphenols are closely related to BC. Bisphenols exposure can promote the progression of BC through multiple complicated and variable molecular mechanisms. Reanalysis of existing data on this topic may reveal molecular markers with clinical value. In this study, we identified four key genes [keratin 14 (<em>KRT14</em>), keratin 5 (<em>KRT5</em>), acyl-CoA synthetase long chain family member 1 (<em>ACSL1</em>) and matrix metallopeptidase 1 (<em>MMP1</em>)] related to both bisphenols exposure and BC by employing the Comparative Toxicogenomics Database (CTD) and The Cancer Genome Atlas Cervical Cancer (TCGA-CESC) dataset; notably, <em>KRT14</em> expression exhibited the most significant difference between tumour and normal tissues. Further analysis of the functions and biological processes associated with <em>KRT14</em> and related regulatory molecules revealed that bisphenols exposure induces BC-promoting characteristics and aggressive behaviour-related signaling pathways, such as the steroid biosynthesis, Forkhead box (<em>FOXO</em>) and prolactin signaling pathways. To confirm the expression and biological effects of <em>KRT14</em>, we conducted relevant experiments. In vitro studies revealed that bisphenols such as bisphenol A (BPA) exposure significantly affected the proliferation, migration, and invasion of MCF-7 cells by inhibiting <em>KRT14</em> expression. Similarly, we also observed a decrease in KRT14 expression in BPA induced abnormal breast tissue in mice. In summary, our study revealed potential genes and pathways associated with bisphenols exposure in BC.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"514 ","pages":"Article 154123"},"PeriodicalIF":4.8,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697690","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":"Parabens exposure and its impact on diabesity: a review.","authors":"Ana Ramalho, Abel Vale, Félix Carvalho, Eduarda Fernandes, Marisa Freitas","doi":"10.1016/j.tox.2025.154125","DOIUrl":"https://doi.org/10.1016/j.tox.2025.154125","url":null,"abstract":"<p><p>Parabens are a family of alkyl esters of 4-hydroxybenzoic acid. The most commonly used include methylparaben, ethylparaben, propylparaben, and butylparaben. These compounds have been reported to disrupt the endocrine system and are believed to affect the central nervous, immune, and reproductive systems, as well as lipid homeostasis, glucose levels, and thyroid function. Given these effects, parabens pose potential health risks, including their possible link to conditions like diabesity - a term describing the dual condition of type 2 diabetes mellitus and obesity. This review explores current literature on how parabens may influence key mechanisms in diabesity, such as gluconeogenesis, glycogenolysis, adipogenesis, insulin resistance, and inflammation. Understanding their role in these metabolic pathways is critical for assessing their contribution to the diabesity epidemic and guiding future research for minimizing their harmful health impacts.</p>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":" ","pages":"154125"},"PeriodicalIF":4.8,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711366","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":"Mice mortality induced by dexmedetomidine is non-alpha2-adrenergic receptor-dependent","authors":"Xiaoxuan Wang ,&nbsp;Yulei Li ,&nbsp;Jiye Yin ,&nbsp;Jiaqi Wang ,&nbsp;Peilan Zhou ,&nbsp;Ruibin Su","doi":"10.1016/j.tox.2025.154122","DOIUrl":"10.1016/j.tox.2025.154122","url":null,"abstract":"<div><div>Dexmedetomidine (DMED) is widely used in sedative anesthetics in clinical settings. Currently, there are no therapeutic interventions available for the lethal toxicity induced by DMED. Administered at doses ranging from 25 to 100 mg/kg intraperitoneally (i.p.), DMED exhibited a dose-dependent fatality in mice. The 50 % lethal dose (LD50) was determined to be 48.5 mg/kg within 24 h and 44.8 mg/kg within 7 days. Alpha2-adrenergic receptor antagonists, namely yohimbine and atipamezole, demonstrated no mitigating effect on the lethal toxicity induced by DMED at the dose of 44.8 mg/kg. Conversely, the administration of atipamezole and yohimbine increased the mortality associated with DMED. By contrast, the imidazoline receptor antagonist idazoxan and the opioid receptor antagonist naloxone significantly attenuated the mortality induced by DMED, thereby prolonging the median survival time following administration of DMED at 44.8 mg/kg (i.p.). Furthermore, the immune modulator imiquimod, calcium sensitizer levosimendan, and TAAR1 antagonist RO5212773 decreased acute mortality without impacting chronic mortality induced by DMED. Histopathological analysis revealed characteristic lung alterations, including capillary hemorrhage, widened alveolar septa, fusion of pulmonary alveoli, and inflammatory cell infiltrate upon DMED exposure. Pretreatment with idazoxan or naloxone inhibited these pathological changes induced by DMED, while atipamezole or yohimbine pretreatment exacerbated lung damage. Elevated levels of serum creatine kinase and myoglobin were noted following DMED administration. However, pretreatment with idazoxan or naloxone decreased the rise of serum creatine kinase and myoglobin. Collectively, these results highlighted the involvement of imidazoline receptors and opioid receptor in DMED mortality.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"514 ","pages":"Article 154122"},"PeriodicalIF":4.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674582","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":"Optimization of the drug-induced cholestasis index based on advanced modeling for predicting liver toxicity","authors":"Annika Drees ,&nbsp;Vahid Nassiri ,&nbsp;Andrés Tabernilla ,&nbsp;Jan Serroyen ,&nbsp;Emmanuel Gustin ,&nbsp;Bruna dos Santos Rodrigues ,&nbsp;Darren Michael Moss ,&nbsp;Ann De Smedt ,&nbsp;Mathieu Vinken ,&nbsp;Freddy Van Goethem ,&nbsp;Julen Sanz-Serrano","doi":"10.1016/j.tox.2025.154119","DOIUrl":"10.1016/j.tox.2025.154119","url":null,"abstract":"<div><div>Cholestatic drug-induced liver injury (cDILI) is a frequent reason for drug failure and withdrawal during premarketing and postmarketing stages of drug development. Strategies for reliable detection of cDILI in early drug development are therefore urgently needed. The drug-induced cholestasis index (DICI) concept was previously introduced as a tool for assessing the cholestatic potential of drug candidates. DICI is calculated as the ratio between the viability values obtained in drug-treated liver cells in the presence and absence of bile acids. The present in vitro study was set up to investigate the applicability of DICI in a novel high-throughput and large sample setting. Furthermore, the improvement of the predictivity of the DICI by introduction of advanced modeling was explored. Fifty-eight well-documented drugs were selected and categorized as drugs inducing cDILI, non-cholestatic DILI (ncDILI), and not inducing DILI (non-DILI). Cultures of human hepatoma HepaRG cells in 3D spheroid configuration were exposed to 9 half-log concentrations of each drug for 1, 3 and 7 days in the absence or presence of a concentrated mixture of human bile acids. The highest concentration of each drug was based on solubility and the maximum concentrations in human plasma (total Cmax). DICI values were computed for all drugs and time points. In addition, the area under the curve ratio and the occurrence of a trend in the cytotoxicity profiles were included as modeling descriptors. As such, 3 time-related scenarios were considered upon modeling, while categories were modeled on a nominal or an ordinal scale. Applying DICI with a cut-off value of 0.8 resulted in a high sensitivity for the cDILI class, but in turn, a low sensitivity for the non- DILI class. From the 28 predictive models generated, the best performing models integrated all descriptors and the ordinal scale for either the 7-day time point from a 3-time-point model or the 3-day time point. While these models were unable to accurately identify ncDILI drugs, the 7-day time point identified 84 % of the cDILI drugs and the 3-day time point correctly identified 94 % of non-DILI drugs. Based on the obtained results, it can be concluded that the reported DICI modeling provides an optimized approach that could be applied in an integrated DILI testing strategy</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"514 ","pages":"Article 154119"},"PeriodicalIF":4.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664554","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":"Thallium induces metallothionein gene expression in Huh-7 human hepatoma cells","authors":"Toshihiko Aki,&nbsp;Takeshi Funakoshi,&nbsp;Kana Unuma","doi":"10.1016/j.tox.2025.154121","DOIUrl":"10.1016/j.tox.2025.154121","url":null,"abstract":"<div><div>Thallium (Tl) is one of the most toxic heavy metals and is found ubiquitously in the earth’s crust. To investigate the cellular responses to and against Tl cytotoxicity, we conducted DNA microarray analysis using three human cell lines of different origins: SH-SY5Y (neuroblast-derived), HEK293T (embryonic kidney-derived), and Huh-7 (hepatoma-derived) cells. All of the ten genes that showed the highest inductions in Huh-7 cells treated with 60 µM Tl₂SO₄ for 72 hours are metallothionein (MT) genes. The induction of the MT genes appears specific to Huh-7 cells; increases of 50–140-fold in the ten MT genes were observed in Huh-7 cells, while the increases were less than 4-fold in HEK293T and SH-SY5Y cells by microarray analysis. Investigation of the pathway responsible for Tl₂SO₄-induced MT expression in Huh-7 cells revealed that the RNA interference-mediated forced downregulation of MTF1 transcription factor resulted in the suppression of Tl₂SO₄-induced MT gene expressions, but not Tl₂SO₄-induced cell death, suggesting that MTF1-mediated MT gene expression is insufficient to protect Huh-7 cells against death by Tl₂SO₄. In contrast, the knockdown of nrf1 worsened Tl₂SO₄-induced cell death without suppressing MT gene expressions. These results indicate that MT gene induction in response to Tl₂SO₄ is mediated at least in part by MTF1 in Huh-7 cells. Nevertheless, MT gene induction through MTF1 seems insufficient to prevent the cell death caused by Tl₂SO₄. Nrf1 appears to be involved in protection against Tl₂SO₄ toxicity through mechanisms other than MT gene induction.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"514 ","pages":"Article 154121"},"PeriodicalIF":4.8,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642961","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":"Subacute exposure of male adolescent rats to 2,2′,5,5′-tetrachlorobiphenyl-4-ol via a polymeric implant causes gene expression changes in the brain and metabolomic disruption in serum","authors":"Hui Wang ,&nbsp;Amanda J. Bullert ,&nbsp;Morgan J. Linahon ,&nbsp;Michael E. Dailey ,&nbsp;Jonathan A. Doorn ,&nbsp;Aloysius J. Klingelhutz ,&nbsp;James A. Ankrum ,&nbsp;Hans-Joachim Lehmler","doi":"10.1016/j.tox.2025.154120","DOIUrl":"10.1016/j.tox.2025.154120","url":null,"abstract":"<div><div>Polychlorinated biphenyls (PCBs) remain an environmental health concern due to their persistence and ongoing release from legacy and emerging sources. 2,2′,5,5′-Tetrachlorobiphenyl (PCB52), a PCB congener frequently detected in the environment and human blood, is oxidized to 2,2′,5,5′-tetrachlorobiphenyl-4-ol (4−52). The neurotoxicity of this hydroxylated (OH-PCB) metabolite remains poorly characterized. In this study, we exposed 4-week-old male Sprague Dawley rats to 4–52 via a polymeric implant drug delivery system grafted in the subcutaneous cavity at 4–52 concentrations of 0 %, 1 %, 5 %, and 10 % in the implant (w/w) for 28 days. Metabolomic analyses were performed in the serum. RNA sequencing, immunofluorescence, and dopamine (DA) measurement with electrochemical detection were used to characterize the effects of 4–52 on the striatum and cerebellum, brain regions implicated in PCB neurotoxicity. Serum metabolomic analysis revealed disruptions in the \"arginine biosynthesis\" pathway following 4–52 exposure. Exposure to 4–52 caused moderate transcriptomic changes in pathways related to \"oxidative phosphorylation\" and \"neuroactive ligand-receptor interactions.\" Immunofluorescence showed no significant alterations in microglial, astrocytic, or apoptotic biomarkers. In the medium dose group, the levels of the DA metabolite DOPAL (3,4-dihydroxyphenylacetaldehyde) were significantly reduced in the striatum. Subsequent multi-omics network analysis identified interactions among OH-PCBs, endogenous metabolites, and the transcriptome. For example, levels of glutamic acid, aspartic acid, choline, and glycerophosphocholine negatively correlated with 4–52 in the striatum. Expression levels of heat shock protein (HSP) family genes, <em>Hsp90b1</em>, <em>Hspa8</em>, and <em>Hspa5</em>, positively correlated with serum metabolites, including proline, 1-methylguanidine, and methionine sulfoxide. These findings identify novel biomarkers and targets of 4–52-induced neurotoxicity.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"514 ","pages":"Article 154120"},"PeriodicalIF":4.8,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650850","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":"Peritubular myoid cells of the testis produce monocyte chemotactic protein 1 upon direct exposure to Mono-(2-Ethylhexyl) phthalate through the IL-1 signaling pathway","authors":"Narayan Acharya,&nbsp;John H. Richburg","doi":"10.1016/j.tox.2025.154118","DOIUrl":"10.1016/j.tox.2025.154118","url":null,"abstract":"<div><div>Mono-(2-ethylhexyl) phthalate (MEHP) is a metabolite of the diester parent compound Di(2-ethylhexyl) phthalate (DEHP), a widespread environmental toxicant known for its harmful effects on Sertoli cells and the subsequent loss of germ cells through apoptosis in postnatal animals. Peritubular myoid cells (PTMCs) produce various signaling factors, including the chemokine monocyte chemotactic protein 1 (MCP-1); however, the MEHP exposure-induced BTB disruption followed by MCP-1 secretion by PTMCs, the recruitment, and activation of macrophages as well as molecular mechanisms that initiate the secretion in the testis has yet to be closely examined. In this study, we demonstrate for the first time that PTMCs generate MCP-1 via the interleukin-1 signaling pathway upon MEHP exposure. Primary PTMCs isolated from the testis of peripubertal rats were cultured and exposed to 100 μM and 200 µM MEHP. Total RNA was used for bulk RNA sequencing, qRT-PCR, and protein lysates for proteomic analysis. Testis and their interstitial fluid (IF) were obtained from MEHP-exposed animals to evaluate the levels of pro-inflammatory cytokines and chemokines in IF through a multiplex assay and in tissue sections through immunofluorescence studies. The RNA sequencing data show significant enrichment of the interleukin-1 signaling pathway after MEHP (200 µM) exposure for 48 hours. This finding is further supported by the qRT-PCR results for select genes associated with the IL-1 signaling pathway, highlighting the crucial role of this pathway in the response of PTMCs to MEHP exposure. In summary, MEHP exposure stimulates MCP-1 production by PTMCs, and mechanistically, the IL-1 signal transduction pathway governs this response. <strong>Keywords</strong>: MCP-1, PTMCs, Rats, Testis, Chemokine, IL-1 signaling</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"514 ","pages":"Article 154118"},"PeriodicalIF":4.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634652","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":"Bisphenol S promotes clear cell renal cell carcinoma progression by modulating the WNT5A-dependent EMT pathway","authors":"Hua Zhang ,&nbsp;Fei Lin ,&nbsp;Bo-Han Lin ,&nbsp;Xiong-Lin Sun ,&nbsp;Qing-Shui Zheng ,&nbsp;Rui Gao ,&nbsp;Yong Wei ,&nbsp;Shao-Hao Chen ,&nbsp;Xue-Yi Xue","doi":"10.1016/j.tox.2025.154117","DOIUrl":"10.1016/j.tox.2025.154117","url":null,"abstract":"<div><div>Bisphenol S (BPS) is widely used in the production of food containers and children's toys and is known to have endocrine-disrupting effects linked to various cancers; however, its role in renal cell carcinoma (RCC) development remains unclear. This study investigates the mechanisms by which BPS may promote RCC progression. The effects of BPS on proliferation and migration were evaluated in HK-2 and 786-O cells using CCK-8, scratch, and Transwell assays. A LASSO regression model and functional analysis were employed to identify candidate genes involved in BPS-related renal cancer progression and to construct a prognostic model, which was validated using Kaplan-Meier and ROC curves. Additionally, the impact of BPS on epithelial-mesenchymal transition (EMT)-related markers was examined. Results showed that BPS did not significantly affect the proliferation of HK-2 and 786-O cells at concentrations of 0–10 μM but significantly enhanced cell migration and invasion, inducing EMT. The LASSO model identified nine key genes associated with BPS-related renal cancer progression, with WNT5A expression positively correlated with BPS concentration. Knockdown of WNT5A significantly inhibited BPS-induced migration of HK-2 and 786-O cells and disrupted the EMT process. These findings demonstrate that BPS promotes HK-2 and 786-O cell migration through the WNT5A-dependent EMT pathway, and inhibition of WNT5A expression can suppress this process. This study provides novel insights into the role of BPS in renal cancer progression and highlights potential therapeutic targets for RCC.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"514 ","pages":"Article 154117"},"PeriodicalIF":4.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630818","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":"Nonclinical safety and biodistribution evaluation of HC009 mRNA vaccine against COVID-19 in rat","authors":"Juan Liu,&nbsp;Xicheng Chen,&nbsp;Chuanqian Chen,&nbsp;Jie Wu,&nbsp;Fengyang Xie,&nbsp;Jing Li,&nbsp;Huafeng Han,&nbsp;Yingying Zhao,&nbsp;Yongsheng Yang","doi":"10.1016/j.tox.2025.154107","DOIUrl":"10.1016/j.tox.2025.154107","url":null,"abstract":"<div><div>mRNA-based technology has been evaluated in clinical trials for rapid control and prevention of emergencies and diseases. HC009, a mRNA vaccine encoding the full-length SARS-CoV-2 spike protein delivered via the QTsome platform, was tested in rats for immunogenicity, toxicity, and biodistribution. For immunogenicity and toxicity, rats received three intramuscular injections of HC009 at 3-week intervals followed by a 4-week observation period. In the biodistribution study, rats received a single intramuscular injection, with mRNA levels measured in organs at various time points. Results showed that HC009 elicited effective, long-lasting humoral immunity and Th1-biased cellular responses. The mRNA primarily localized to the injection site and spleen, with no observed vaccine-related toxicological reactions. These findings support HC009’s potential for inducing an effective immune response with a favorable safety profile, warranting further clinical investigation.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"514 ","pages":"Article 154107"},"PeriodicalIF":4.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597830","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}