{"title":"Investigation of some metal levels in people using electronic cigarettes and IQOS.","authors":"Yunus Yüce, Benay Can Eke","doi":"10.1080/15376516.2025.2506796","DOIUrl":"10.1080/15376516.2025.2506796","url":null,"abstract":"<p><strong>Objectives: </strong>There has been a sharp increase in the use of e-cigarettes and heated tobacco products (HTPs) in the last decade. Related to the increase in the use, serious public health debates have been caused by the safety and risks of these products. Particularly due to the exposure to a lot of toxic substances, including heavy metals, there has been an increasing concern over their health effects. Heavy metals such as lead, arsenic, mercury, and cadmium are environmental pollutants poising significant health risks. These metals have a disposition to accumulate in the human body over time. Even at lower levels of exposure, they might lead to multiple organ damage and adverse health effects, including neurotoxicity, nephrotoxicity, and being carcinogenicity.</p><p><p>This study tests the idea that using electronic cigarettes (e-cigarettes) and IQOS devices raises the levels of metals in urine and that the amount of increase depends on which product is used. The study aims to look at the levels of lead, cadmium, nickel, zinc, and selenium in the urine of cigarette smokers, e-cigarette users, IQOS users, and nonsmokers; to check for significant differences in metal levels between these groups (with a significance level set at <i>p</i> < 0.05); to compare the metal levels found with safety limits; and to explore if there's a link between the metal levels in urine and the type of product used (cigarettes, IQOS, or e-cigarettes).</p><p><strong>Method: </strong>This study aimed to compare the trace element, heavy element, and nicotine exposures of individuals who smoke (<i>n</i> = 39), use e-cigarettes (<i>n</i> = 28), use IQOS (<i>n</i> = 20), and do not use tobacco or tobacco products (<i>n</i> = 30) while living in Ankara, Türkiye. In order to evaluate the element levels of the participants, the levels of lead, cadmium, nickel, zinc, and selenium metals in their urine were determined using inductively coupled plasma mass spectrometry (ICP-MS), and nicotine exposures were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS).</p><p><strong>Results: </strong>The measurement showed that lead levels were higher in IQOS users (8.51 ng/g creatinine) and smokers (3.67 ng/g creatinine) compared to e-cigarette users (1.38 ng/g creatinine), and this difference was statistically significant (<i>p</i> < 0.05). In addition, a statistically significant difference was found between the cotinine level and lead level of the smoking and IQOS groups (<i>p</i> ˂ 0.05). No statistically significant difference was found between the groups in terms of cadmium level (<i>p</i> > 0.008). Nickel level was found to be higher in e-cigarette (3.43 ng/g creatinine) and IQOS (3.84 ng/g creatinine) users than in the smoking group (0.99 ng/g creatinine). In terms of nickel, a statistically significant difference was found between the e-cigarette and IQOS groups and both the smoking and control groups (<i>p</i> ˂ 0.05). No statistically signif","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1023-1038"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Faezeh Jahedi, Neamatollah Jaafarzadeh Haghighi Frad, Mohammad Ali Khaksar, Parisa Rashidi, Farhad Safdari, Zahra Mansouri
{"title":"Nano and microplastics: unveiling their profound impact on endocrine health.","authors":"Faezeh Jahedi, Neamatollah Jaafarzadeh Haghighi Frad, Mohammad Ali Khaksar, Parisa Rashidi, Farhad Safdari, Zahra Mansouri","doi":"10.1080/15376516.2025.2509745","DOIUrl":"10.1080/15376516.2025.2509745","url":null,"abstract":"<p><p>Plastics are extensively used materials with a long environmental lifespan, posing significant risks to human health and the environment. Global plastic consumption has surged, with plastic waste expected to triple by 2060. The primary concern is the breakdown of plastics into nano and micro-sized particles, which can enter the body and have been detected in various organs and tissues. This review systematically examines the effects of micro and nanoplastics (MNPs) on the endocrine system using <i>in vitro</i> and <i>in vivo</i> experimental models. Following PRISMA guidelines, articles were sourced from databases like PubMed, Web of Science, and Scopus. After screening for relevance and removing duplicates and non-English articles, 103 articles focusing on the endocrine effects of MNPs were selected. MNPs can disrupt endocrine functions, altering reproductive hormones and gene expression patterns. <i>In vivo</i> exposure to MNPs increases inflammatory markers such as TNF-α, IL-6, IL-1β, and NF-κB, leading to apoptosis, inflammation, and oxidative stress. These disruptions impact the gonads, thyroid glands, and hormone secretion from the pituitary and hypothalamus. Most studies focus on terrestrial animals, with polystyrene being the most commonly used polymer. Future research should explore various plastic polymers, longer exposure durations, a broader range of concentrations, and human-level studies to better understand the toxicity of plastic particles. Reducing exposure to these pollutants requires legal changes, consumer behavior adjustments, and increased public awareness. Understanding the underlying processes can help propose methods to mitigate risks and protect human health.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"865-893"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144161145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evaluation of acute, subacute, subchronic, reproductive, and genotoxicity of a standardized extract from the bark of <i>Oroxylum indicum</i>.","authors":"Anju Majeed, Anjali Pandey, Chaitra Gurumallesha, Sarang Bani","doi":"10.1080/15376516.2025.2508755","DOIUrl":"10.1080/15376516.2025.2508755","url":null,"abstract":"<p><p><i>Oroxylum indicum</i> extract (OIE), prepared from its dried bark, known for neuroprotective and cognitive health support, is evaluated. <i>Oroxylum indicum,</i> the Indian Trumpet Tree, is traditionally known for its numerous medicinal benefits. Almost every part of the plant has been traditionally applied to treat many conditions such as stomachache, rheumatism, jaundice, cough, pharyngitis, acute and chronic bronchitis. Various researchers have demonstrated biological activities including antioxidant, and anti-inflammatory, immunomodulatory, analgesic, anti-cancer, anthelmintic, hepatoprotective, antiulcer, anti-diarrheal, cardioprotective, anti-diabetic, anti-epileptic, wound healing, properties. Since very little scientific evidence was available on safety assessment of OIE, a detailed toxicological evaluation of OIE was executed to ensure its safety for human administration and to harness its potential therapeutic applications. The present study evaluated the acute, subacute, subchronic, and reproductive toxicity of OIE in rodents. Also, the mutagenic potential was evaluated with the bacterial reverse mutation assay and the mammalian bone marrow micronucleus test.</p><p><p>No treatment-related study findings were observed, and a No Observed Adverse Effect Level of 400 mg/kg body weight was established in subacute, subchronic, reproductive/developmental toxicity studies. In addition, the findings of genotoxicity as evaluated by <i>in vitro</i> bacterial reverse mutation assay, and <i>in vivo</i> mammalian bone marrow micronucleus test in mice showed that OIE did not induce any mutagenic effects. Henceforth, this toxicological evaluation confirms that oral administration of OIE was found to be safe in rodents, non-mutagenic, without any adverse effects. This study positively impacts in encouraging the use of OIE in various therapeutic applications ensuring its safety.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1039-1056"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Clinical and forensic toxicology of bromism and bromoderma: mechanisms, diagnosis, and treatment.","authors":"Joana Coelho-Silva, Juliana Faria, Ricardo Jorge Dinis-Oliveira","doi":"10.1080/15376516.2025.2522220","DOIUrl":"10.1080/15376516.2025.2522220","url":null,"abstract":"<p><p>Bromism is a syndrome that results from bromide intoxication. It is difficult to diagnose since it mimics a myriad of psychiatric and dermatological disturbances. Historically, the most common sources have been drug ingestion or contaminated drinks. This work aims to thoroughly review all the state-of-the-art aspects of bromism and bromoderma, including its pathophysiology, diagnosis, treatment, and other relevant clinical and forensic features. In this context, a comprehensive search was conducted in PubMed (U.S. National Library of Medicine) without time restrictions. Bromism may occur in individuals of any age or gender, but it is more frequent in women. In children, it usually occurs under therapy for resistant epilepsy or is breastfed by mothers who ingested bromide and may manifest as bromoderma. In adults, bromism manifests with psychiatric and neurological signs such as hallucinations, delusions, or ataxia. Pseudohyperchloremia with a negative anion gap is highly suggestive of the diagnosis. Treatment requires the removal of bromide, which is achieved by <i>per os</i> or intravenous saline administration or even hemodialysis. Although bromism is not usually observed in clinical and forensic practice, it is still related to the administration of controlled or immediate-release formulations, mainly analgesics or antiepileptic drugs, as well as internet-purchased supplements.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"943-968"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Neodymium nitrate promotes the apoptosis of mouse liver cells via Bcl2l1/Caspase 3 pathway.","authors":"Jing Leng, Ning Wang, Xiu-Li Chang, Xiao-Peng Zhang, Jing Xu, Zheng-Li Yang, Ke-Lei Qian, Zhi-Qing Zheng, Gong-Hua Tao, Xu-Dong Jia, Ping Xiao, Xin-Yu Hong","doi":"10.1080/15376516.2025.2501253","DOIUrl":"10.1080/15376516.2025.2501253","url":null,"abstract":"<p><strong>Background: </strong>Neodymium, as a strategic rare earth element (REE), has demonstrated bioaccumulative potential and can permeate human systems through inhalation of airborne particulates, ingestion of contaminated food/water, and dermal absorption from soil matrices, ultimately eliciting multi-organ toxicological manifestations. However, the hepatotoxicological profile of neodymium species and their pathophysiological mechanisms remain inadequately characterized. Neodymium nitrate (Nd(NO<sub>3</sub>)<sub>3</sub>), the predominant water-soluble neodymium species, exhibits marked bioavailability with particular hepatic tropism.</p><p><strong>Objective: </strong>This study aims to investigate the effects of neodymium nitrate on apoptosis of mouse liver cells and its underlying molecular mechanisms.</p><p><strong>Results: </strong>Mouse liver cell line AML12 was treated with gradient concentrations of neodymium nitrate. The results showed that neodymium nitrate inhibited liver cell proliferation, induced apoptosis, and exhibited a dose-dependent relationship. Western blotting and quantitative real-time PCR (qRT-PCR) revealed that neodymium nitrate suppressed Bcl2l1 transcription and activated the proteolysis of Caspase 3. To further explore the molecular mechanism, Bcl2l1 protein was overexpressed in mouse liver cells. The findings indicated that overexpression of Bcl2l1 rescued neodymium nitrate-induced apoptotic phenotypes and attenuated Caspase 3 cleavage.</p><p><strong>Conclusion: </strong>The present data suggest that neodymium nitrate induces apoptosis of mouse liver cells through the Bcl2l1/Caspase 3 pathway. However, further studies are called for to substantiate this view, as the findings may provide critical mechanistic evidence for revising the toxicological risk assessment frameworks of rare earth elements.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"993-1002"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The possible mechanisms of trans fatty acid effects on digestive disorders based on computational toxicology: a case study of elaidic acid.","authors":"Chenyang Yu, Fule Wang, Xinfang Zhang, Changchuan Bai, Guanhua Lv","doi":"10.1080/15376516.2025.2503873","DOIUrl":"10.1080/15376516.2025.2503873","url":null,"abstract":"<p><p>Trans fatty acids (TFAs) are potential health risk factors generated during food processing, and their mechanisms of association with digestive diseases remain incompletely elucidated. This study focused on elaidic acid (EA), integrating computational toxicology and molecular docking to systematically analyze its molecular mechanisms in regulating functional dyspepsia (FD), gastric cancer (GC), nonalcoholic fatty liver disease (NAFLD), and colorectal cancer (CRC) through multi-target networks. Protein Interaction Networks were constructed by screening EA and disease-intersecting targets, enriching and analyzing key pathways, and validating the binding ability of core targets. Results showed that EA shared 22, 67, 56, and 72 common targets with FD, GC, NAFLD, and CRC, respectively. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that EA acts through pathways including lipid metabolism dysregulation, inflammatory response, and chemical carcinogenesis-receptor activation. Molecular docking confirmed binding affinities between EA and core targets. The present study suggests that EA may promote the progression of digestive diseases through a multi-target-multi-pathway model, providing a new perspective for the study of the toxicity mechanism of TFA and food safety prevention and control.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1011-1022"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144049980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mennatallah Mahmoud Ahmed Mohamed, Nada A Yousri, Noura Hassan Khamis, Shimaa Abdel Baset Abdel Hakim, Samar Hisham Elsayed, Elzahraa Ahmed Elrefaie Ali
{"title":"Evaluation of polyethylene microplastics toxicity using Nrf2/ARE and MAPK/Nrf2 signaling pathways.","authors":"Mennatallah Mahmoud Ahmed Mohamed, Nada A Yousri, Noura Hassan Khamis, Shimaa Abdel Baset Abdel Hakim, Samar Hisham Elsayed, Elzahraa Ahmed Elrefaie Ali","doi":"10.1080/15376516.2025.2527154","DOIUrl":"10.1080/15376516.2025.2527154","url":null,"abstract":"<p><p>Microplastics (MPs) have emerged as a serious global environmental threat due to their resistance to degradation and persistence in ecosystems. Given their potential risks to human health, it is essential to thoroughly investigate the mechanisms of toxicity and associated health consequences. This study examined the toxicological and reproductive effects of varying doses of polyethylene microplastics (PE-MPs) in 120 male and female Sprague Dawley rats. A statistically significant, dose-dependent increase in malondialdehyde levels was observed, along with a reduction in catalase activity. Furthermore, alterations were detected in sexual hormone levels and disruptions were noted in both the Kelch-like ECH-associated protein 1 (Keap1)-Nrf2-ARE (antioxidant response element) and p38 MAPK-Nrf2 signaling pathways. PE-MP exposure also produced marked histopathological changes in the testes and ovaries. These findings indicate that reproductive toxicity from PE-MPs is associated with impairments in the Keap1-Nrf2-ARE and p38 MAPK-Nrf2 pathways. The results underscore the importance of limiting MP exposure to mitigate potential health hazards and provide new data on the potential mechanisms of toxicity of MPs.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1118-1137"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Potential of Fenfuro<sup>®</sup>, a novel, standardized <i>Trigonella foenum-graecum</i> (Fenugreek) seed extract, in ameliorating glycation-mediated amyloidogenesis.","authors":"Sreemoyee Saha, Pawan Kumar, Manashi Bagchi, Debalina Bhattacharya, Sudipta Chakraborty, Sanjoy Chakraborty, Samudra Prosad Banik, Debasis Bagchi","doi":"10.1080/15376516.2025.2567419","DOIUrl":"https://doi.org/10.1080/15376516.2025.2567419","url":null,"abstract":"<p><p>The potential of Trigonella foenum-graecum or fenugreek seed extract in alleviating chronic hyperglycemia is supported by scientific evidence. In addition to its role in optimizing the insulin signaling pathway, fenugreek extract can also prevent the generation of Advanced Glycation End products (AGE) by sequestration of reactive carbonyl groups involved in the formation of Schiff base with lysine and arginine residues of protein side chains. In the present work, a patented and standardized extract of Fenfuro<sup>®</sup> was found to reduce AGE fluorescence by 75%, along with a corresponding decrease in Thioflavin T fluorescence of nearly 85%. It was determined that these significant spectral changes were due to a combined effect of the protein as well as non-protein part of the extract and not attributable to any single bioactive component. The precipitated protein from the extract itself showed Thio-T fluorescence and gave a single band around the 65 kD MW range. The non-protein supernatant, when incubated with the glycated protein, gave an enhanced AGE as well as Thio-T fluorescence thus negating any possibility of plant extract mediated quenching of fluorescence leading to false interpretations. 8-Anilinonaphthalene-1-sulfonic acid (ANS) fluorescence spectra indicated that the extract provided substantial protection against thermal denaturation.The results collectively provided significant insights for exploring newer avenues of fenugreek-based therapeutics for treating both diabetes and neurodegeneration.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-10"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Catalina García-Vielma, Elva Irene Cortés-Gutiérrez, Irma Edith Carranza-Torres, Nancy Elena Guzmán-Delgado, Martha Imelda Dávila-Rodríguez, Ricardo Martín Cerda-Flores, Pilar Carranza-Rosales
{"title":"An <i>ex vivo</i> model to evaluate DNA damage by comet assay in breast-cancer tissue.","authors":"Catalina García-Vielma, Elva Irene Cortés-Gutiérrez, Irma Edith Carranza-Torres, Nancy Elena Guzmán-Delgado, Martha Imelda Dávila-Rodríguez, Ricardo Martín Cerda-Flores, Pilar Carranza-Rosales","doi":"10.1080/15376516.2025.2503872","DOIUrl":"10.1080/15376516.2025.2503872","url":null,"abstract":"<p><p>Single cell gel electrophoresis (comet assay) is a research tool known for its use in the assessment of DNA damage in which peripheral blood lymphocytes are used as a cellular model. The objective of this study was to adapt the comet assay to fresh normal and tumor breast tissue explants to assess DNA damage. Representative samples were obtained from nine patients with infiltrating ductal adenocarcinoma during the time of surgical intervention for the resection of the tumor. One hundred micrometer thick explants were prepared from normal and tumor breast tissue using a tissue slicer. Explants were harvested into six-well microplates with 4 mL of sterile serum-free Dulbecco's modified Eagle's medium/Ham's F12 medium at 4 °C for immediate processing of the comet assay. The results indicated that the comet assay can be used to analyze DNA damage in tumors and healthy breast tissue in an <i>ex vivo</i> model that allows visualization of the level of DNA damage. Compared to non-tumor cells, DNA damage in breast cancer was significantly increased (<i>p</i> < 0.05); furthermore, DNA damage was higher in samples treated with H<sub>2</sub>O<sub>2</sub> (positive control) and confirmed that cells in the explants can interact with the chemicals tested, as well as the functionality of the technique. The comet assay using fresh tissue explants represents an alternative tool with potential to identify DNA damage in tumor tissue and to study new drugs to personalize the use of DNA-damaging therapies.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1003-1010"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cinobufagin induced myocardial cell toxicity in H9c2 cells via inhibiting histone methyltransferase SMYD1 expression.","authors":"Huimin Wu, Chen Wang, Hong Zhang, Qi Zhang, Jiahe Wang, Ying Wang, Langqun Chen, Siyu Cheng, Jiahui Ying, Yujie Xiang, Yiran Cheng, Jing Ye, Liang Zhang","doi":"10.1080/15376516.2025.2520817","DOIUrl":"10.1080/15376516.2025.2520817","url":null,"abstract":"<p><p>Cardiotoxicity of traditional Chinese medicines (TCMs) is an important factor in pharmacogenetic cardiovascular diseases, which directly affects the clinical use of TCM. Recently, cinobufagin (CBG), the active substance of Toad venom, has shown as a potential anti-tumor natural product. However, its cardiotoxicity limits the clinical application and the intrinsic mechanism is unclear. Here, we found that CBG induced oxidative stress and cell apoptosis in rat cardiomyocytes (H9c2), which caused cardiomyocyte injury. SET and MYND domain containing 1 (SMYD1) is a histone methyltransferase containing a SET-MYND domain, which is specifically expressed only in cardiomyocytes and skeletal muscle cells. RNA-Seq analysis revealed that the expression of SMYD1 was significantly decreased in the CBG treated H9c2 cells. Overexpression of SMYD1 alleviated CBG-induced myocardial injury, while knockdown of SMYD1 did the opposite. To summary, our study indicated that CBG induced cell apoptosis and oxidative stress <i>via</i> suppressing the expression of SMYD1 and ultimately leaded to myocardial toxicity. This research revealed the side-effects of CBG in myocardial toxicity and provided mechanism basis in specific disease conditions for CBG therapy.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1089-1102"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}