Archives of Toxicology最新文献_第3页

A coral-derived neuropeptide suppresses pentylenetetrazol (PTZ)-induced epileptic seizures and improves recognition memory deficits by modulating NPY-Y1R. 一种珊瑚源神经肽通过调节NPY-Y1R抑制戊四唑（PTZ）诱导的癫痫发作并改善识别记忆缺陷。

IF 6.9 2区医学

Archives of Toxicology Pub Date : 2025-09-26 DOI: 10.1007/s00204-025-04164-3

Qian Chen, Congshuang Deng, Xiaoshan Huang, Aili Wang, Nan Xu, Kaixun Cao, Min Yang, Shang Li, Qiumin Lu, Guiyi Gong, Simon Ming-Yuen Lee

{"title":"A coral-derived neuropeptide suppresses pentylenetetrazol (PTZ)-induced epileptic seizures and improves recognition memory deficits by modulating NPY-Y1R.","authors":"Qian Chen, Congshuang Deng, Xiaoshan Huang, Aili Wang, Nan Xu, Kaixun Cao, Min Yang, Shang Li, Qiumin Lu, Guiyi Gong, Simon Ming-Yuen Lee","doi":"10.1007/s00204-025-04164-3","DOIUrl":"https://doi.org/10.1007/s00204-025-04164-3","url":null,"abstract":"Epilepsy is a prevalent neurological disorder characterized by recurrent and unprovoked seizures. Despite the availability of anti-epileptic drugs (AEDs), a significant number of patients are still suffering from drug-resistant epilepsy. Neuropeptide Y (NPY) signaling system has emerged as a potential target for the development of anti-epileptic drugs due to its modulation of epileptic activity. In this study, we investigated the therapeutic potential of our previously discovered Scleractinia-derived NPY-like peptide (TpNPY) in seizure disorders. The anticonvulsant effects of TpNPY were evaluated using PTZ-induced seizures in zebrafish and mice in vivo. Furthermore, the underlying molecular mechanisms of TpNPY were assessed using glutamate-induced excitotoxicity models in HT22 mouse hippocampal cells in vitro. Our findings indicated that TpNPY could alleviate PTZ-induced seizure behavior, reduce the expression of seizure-associated immediate-early genes and the production of Reactive Oxygen Species (ROS) in zebrafish. In mice, TpNPY improved seizure behaviors, decreased inflammatory cytokine levels, and ameliorated abnormal glial activation in a PTZ kindling epileptic model. Besides, the administration of TpNPY could attenuate the PTZ-induced anxiety levels and improve recognition memory deficits. Moreover, TpNPY promotes neurogenesis and neural synaptic plasticity through the BDNF/TrkB signaling pathway. Additionally, TpNPY restored cell injury and attenuated oxidative stress in glutamate-challenged HT22 cells through the Nrf2/HO-1 signaling pathway. These results highlight the potential therapeutic efficacy of TpNPY in the treatment of seizures and provide new insights into the development of coral-derived anti-epileptic peptide-based drugs.","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chemical disruption of placental thyroid hormone signalling: a systematic review that highlights sex-specific effects. 胎盘甲状腺激素信号的化学破坏：一项强调性别特异性效应的系统综述。

IF 6.9 2区医学

Archives of Toxicology Pub Date : 2025-09-25 DOI: 10.1007/s00204-025-04203-z

Julia Swan, D Zhurenko, K M Huttunen, J Rysä

{"title":"Chemical disruption of placental thyroid hormone signalling: a systematic review that highlights sex-specific effects.","authors":"Julia Swan, D Zhurenko, K M Huttunen, J Rysä","doi":"10.1007/s00204-025-04203-z","DOIUrl":"https://doi.org/10.1007/s00204-025-04203-z","url":null,"abstract":"Thyroid hormones are crucial for growth, brain development, metabolism, and organ maturation in developing foetuses. Until 12-14 weeks of gestation, the foetus depends on maternal thyroid hormones before its own thyroid gland begins functioning. Environmental chemical and medication exposure during pregnancy may affect the thyroid hormone supply to the foetus by interfering with placental transport carriers and metabolism. This systematic review evaluated chemical effects on thyroid hormone passage from maternal to foetal circulation, modulated by transporters and enzymes. A search of PubMed, Scopus, and Web of Science identified 24 relevant studies published between 1900 and 2024, including 4 epidemiological studies, 8 in vivo animal studies, and 15 in vitro studies. The review found evidence that persistent organic pollutants, flame retardants, endocrine disrupting chemicals, pharmaceuticals, and other substances can disrupt placental thyroid hormone signalling through various mechanisms. These include alterations in transporter expression and enzyme activity in the placenta. Several studies observed sex-specific effects, with male and female foetuses showing different responses to chemical exposure. In some cases, sex differences were in the degree of change, while in others, the same chemical had opposite effects based on foetal sex. However, many studies used choriocarcinoma cell lines, which may not fully replicate human placental processes. This review highlights the need for further research to elucidate chemical exposure's impact on foetal thyroid hormone status and the role of foetal sex using human physiologically relevant models.","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fast and reliable in vitro activity-based detection of synthetic cannabinoid receptor agonists in e-liquids. 合成大麻素受体激动剂体外快速、可靠的活性检测方法。

IF 6.9 2区医学

Archives of Toxicology Pub Date : 2025-09-25 DOI: 10.1007/s00204-025-04193-y

Axelle Timmerman, Cathelijne Lyphout, Nick Verougstraete, Vera Coopman, Christophe Stove

{"title":"Fast and reliable in vitro activity-based detection of synthetic cannabinoid receptor agonists in e-liquids.","authors":"Axelle Timmerman, Cathelijne Lyphout, Nick Verougstraete, Vera Coopman, Christophe Stove","doi":"10.1007/s00204-025-04193-y","DOIUrl":"https://doi.org/10.1007/s00204-025-04193-y","url":null,"abstract":"Synthetic cannabinoid receptor agonists (SCRAs) are marketed as 'legal' cannabis alternatives, but are often much more potent and toxic, increasing the risk of (severe) intoxication. Initially sold as herbal preparations, SCRAs are now increasingly found in e-liquids due to the growing popularity of e-cigarettes. Traditional analytical methods, such as (high-resolution) mass spectrometry, can detect these substances but face limitations regarding time and cost, and require sophisticated equipment and frequently updated mass spectral libraries. Additionally, the continuous emergence of new SCRAs, aiming at evading legislation or detection, further challenges these methods. Activity-based screening, evaluating a sample's inherent cannabinoid activity rather than relying on structural identification, offers an effective alternative. Here, an in vitro CB1/β-arrestin2 recruitment assay utilizing the NanoBiT® principle was, for the first time, applied to an e-liquid from an intoxicated patient, demonstrating strong cannabinoid activity. Employing the assay to screen a set of 23 e-liquids identified six SCRA positive e-liquids. Moreover, in five e-liquids, a decreased CB1 activity was observed and experimentally confirmed to be attributable to the presence of the natural cannabinoid cannabidiol (CBD). As this could potentially result in a false-negative screening, an adapted protocol was evaluated, incorporating the injection of a CB1 agonist, CP55,940, while the assay was running. This improved methodology allowed the detection of both SCRAs and CBD in e-liquids. Furthermore, the fast and 'untargeted' nature of this approach makes it a future-proof method for the detection of SCRAs, serving as an effective first-line screening tool, complementing the conventional analytical techniques.","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

One-pot stable isotope dilution- and LC-MS/MS-based quantitation of guanine, O⁶-methylguanine, and N⁷-methylguanine. 鸟嘌呤、o6 -甲基鸟嘌呤和n7 -甲基鸟嘌呤的一锅稳定同位素稀释和LC-MS/ ms定量分析。

IF 6.9 2区医学

Archives of Toxicology Pub Date : 2025-09-24 DOI: 10.1007/s00204-025-04195-w

Chen Sun, Wei Li, Ying Peng, Jiang Zheng

{"title":"One-pot stable isotope dilution- and LC-MS/MS-based quantitation of guanine, O6-methylguanine, and N7-methylguanine.","authors":"Chen Sun, Wei Li, Ying Peng, Jiang Zheng","doi":"10.1007/s00204-025-04195-w","DOIUrl":"https://doi.org/10.1007/s00204-025-04195-w","url":null,"abstract":"Nitrosamines (NAs) are a class of compounds designated as probable human carcinogens by the IARC, acting DNA mutagens, participating in alkylating DNA at both N7- and O6- positions of guanine, particular for N-nitrosodimethylamine (NDMA). In the present study, we report the development of an LC-MS/MS-based assay to simultaneously measure guanine (Gua), O6-methylguanine (6MGua), and N7-methylguanine (7MGua) in DNA hydrolysates. With the use of three stable isotope internal standards (6-CD3-Gua, 7-CD3-Gua, and Gua-13C2,15N), validation, i.e. determination of selectivity, precision, accuracy, extraction recovery, matrix effect, stability, and feasibility was evaluated by use of the approach developed. This method was used for simultaneous determination of the levels of Gua, 6MGua, and 7MGua in DNA acidic hydrolytes present in a series of samples from human and rat primary hepatocyte treated with NDMA. The stable isotope dilution-based approach was proven to be selective, sensitive, accurate, and convenient, which is a good and convincing in vitro assay for the quantitative analysis of DNA methylation such as 6MGua and 7MGua in Gua.","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Integrating immune adverse outcome pathways into vaccine safety evaluation. 将免疫不良后果途径纳入疫苗安全性评价。

IF 6.9 2区医学

Archives of Toxicology Pub Date : 2025-09-23 DOI: 10.1007/s00204-025-04202-0

Laxit K Bhatt, Pankaj Dwivedi, Ramchandra K Ranvir, Rajesh Sundar, Mukul R Jain

{"title":"Integrating immune adverse outcome pathways into vaccine safety evaluation.","authors":"Laxit K Bhatt, Pankaj Dwivedi, Ramchandra K Ranvir, Rajesh Sundar, Mukul R Jain","doi":"10.1007/s00204-025-04202-0","DOIUrl":"https://doi.org/10.1007/s00204-025-04202-0","url":null,"abstract":"Adverse outcome pathways (AOPs) have become an internationally recognized framework for chemical risk assessment, linking molecular initiating events (MIEs) to adverse outcomes through measurable key events. Despite their regulatory acceptance in toxicology, no systematic AOPs have yet been developed for vaccines to our knowledge. This commentary argues that extending the AOP paradigm to vaccine adjuvants is both timely and potentially feasible. Adjuvants are chemically defined entities that reproducibly engage innate immune pathways, making them more tractable starting points for immune AOP construction than antigens, which are variable and context-dependent. We illustrate this concept through three exploratory AOP sketches - systemic inflammation, autoimmunity, and hypersensitivity, and provide exemplar biomarker-pathway-adjuvant linkages as a prototype roadmap. Such efforts are not intended to replace existing preclinical, clinical, or pharmacovigilance systems, but to complement them with structured mechanistic context. We propose these as exploratory frameworks to be iteratively refined as evidence accumulates, recognising the complexity and context‑dependence of immune responses. By framing vaccine safety within transparent, testable pathways, immune AOPs could enhance mechanistic understanding of rare adverse events, guide hypothesis-driven use of new approach methodologies (NAMs), and strengthen confidence in vaccine safety science.","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Gemfibrozil’s cytotoxicity and DNA protection: PPAR-α agonism overrides genotoxicity in lymphocytes 吉非罗齐的细胞毒性和DNA保护：PPAR-α激动作用优于淋巴细胞的遗传毒性。

IF 6.9 2区医学

Archives of Toxicology Pub Date : 2025-09-22 DOI: 10.1007/s00204-025-04199-6

Mehmet Tahir Husunet, Erman Salih Istifli, Busra Boz, Rumeysa Mese, Amine Hafis Abdelsalam, Hasan Basri Ila

{"title":"Gemfibrozil’s cytotoxicity and DNA protection: PPAR-α agonism overrides genotoxicity in lymphocytes","authors":"Mehmet Tahir Husunet, Erman Salih Istifli, Busra Boz, Rumeysa Mese, Amine Hafis Abdelsalam, Hasan Basri Ila","doi":"10.1007/s00204-025-04199-6","DOIUrl":"10.1007/s00204-025-04199-6","url":null,"abstract":"<div>Fibrates, carboxylic acid derivatives used in hypercholesterolemia treatment, are classified as non-genotoxic carcinogens. However, induce oxidative stress and DNA damage. This study investigates the genotoxic effects of gemfibrozil (GMF), a hypolipidemic agent, on human peripheral blood lymphocytes through cytokinesis-block micronucleus (CBMN) and alkaline comet assays. Plasmid DNA (pBR322) assessed GMF’s DNA protective effects, while total oxidant (TOS) and antioxidant (TAS) status quantified oxidative stress modulation. Molecular docking simulations evaluated non-covalent interactions of GMF against DNA and peroxisome proliferator-activated receptor alpha (PPAR-α). At 25–250 µg/mL, GMF did not induce micronuclei (24–48 h) but triggered significant DNA fragmentation at 250 µg/mL (p < 0.01). GMF significantly reduced cytokinesis-block proliferation index (CBPI) across all concentrations and durations (p < 0.001), except 25 µg/mL (48 h). In a cell-free system, GMF exhibited a complex, bimodal protective effect against H₂O₂-induced plasmid damage, offering protection at 25 and 175 µg/mL but not at 100 µg/mL. However, TOS/TAS levels remained unaltered. Molecular docking demonstrated weak DNA binding (ΔG = −5.93 kcal/mol) compared to mitomycin C (ΔG = −7.25 kcal/mol), but strong PPAR-α affinity (ΔG = −7.40 kcal/mol). These findings suggest GMF exerts cytotoxicity via disrupted cell division kinetics rather than direct DNA damage or oxidative stress. Despite a low genotoxic risk of GMF in vitro. In vivo studies are critical to confirm safety.</div>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":"99 11","pages":"4649 - 4663"},"PeriodicalIF":6.9,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Regulated cell death in endometrial diseases: from molecular mechanisms to targeted therapies. 子宫内膜疾病中的细胞死亡调控：从分子机制到靶向治疗。

IF 6.9 2区医学

Archives of Toxicology Pub Date : 2025-09-22 DOI: 10.1007/s00204-025-04192-z

Duo Zi, Jing Sun, Na Zuo, Tingting Li, Junzhi Liang, Jia Hu, Zhijing Na, Hao Zhang, Lixia He, Da Li

引用次数: 0

piR-16404 drives ferroptotic liver injury via CASTOR1/mTORC1/GPX4 dysregulation in HepG2 cells and mice: a novel toxicity mechanism of N, N-dimethylformamide. piR-16404在HepG2细胞和小鼠中通过CASTOR1/mTORC1/GPX4失调驱动铁性肝损伤：N， N-二甲基甲酰胺的一种新的毒性机制

IF 6.9 2区医学

Archives of Toxicology Pub Date : 2025-09-22 DOI: 10.1007/s00204-025-04198-7

Wanli Ma, Xiaoyu Huo, Ruoxi Li, Jingjing Xing, Lin Xu, Dianke Yu

{"title":"piR-16404 drives ferroptotic liver injury via CASTOR1/mTORC1/GPX4 dysregulation in HepG2 cells and mice: a novel toxicity mechanism of N, N-dimethylformamide.","authors":"Wanli Ma, Xiaoyu Huo, Ruoxi Li, Jingjing Xing, Lin Xu, Dianke Yu","doi":"10.1007/s00204-025-04198-7","DOIUrl":"https://doi.org/10.1007/s00204-025-04198-7","url":null,"abstract":"N, N-dimethylformamide (DMF), a widely used industrial solvent including new energy technologies, induces hepatotoxicity through poorly understood mechanisms. This study demonstrates that DMF exposure triggers ferroptosis in hepatocytes, characterized by glutathione depletion, iron accumulation, and lipid peroxidation both in vitro (0-160 mM DMF exposure) and in vivo (0, 750 mg/kg and 1500 mg/kg of DMF exposure). Transmission electron microscopy revealed ferroptotic mitochondrial damage, while biochemical assays confirmed GPX4 suppression and elevated 4-HNE levels. piRNA sequencing identified piR-16404 as significantly downregulated following DMF exposure. Functional studies showed piR-16404 overexpression attenuated DMF-induced ferroptosis by targeting CASTOR1, an arginine sensor for mTORC1. Mechanistically, piR-16404 binds CASTOR1's 3'-UTR to promote its degradation, thereby reactivating mTORC1-GPX4 signaling. In vivo supplementation of agomir-piR-16404 ameliorated DMF-induced liver injury, reducing serum ALT/AST by 42-58% and restoring hepatic GPX4 expression. Our findings establish ferroptosis as a key pathway in DMF hepatotoxicity and identify the piR-16404-CASTOR1-mTORC1 axis as a novel therapeutic target, providing new insights into environmental chemical-induced liver injury mechanisms.","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Outsmarting generic legislation: 4 years into the cat-and-mouse game of the synthetic cannabinoid receptor agonist market since the Chinese ban in 2021. 战胜仿制药立法：自2021年中国颁布禁令以来，合成大麻素受体激动剂市场的猫捉老鼠游戏已经持续了4年。

IF 6.9 2区医学

Archives of Toxicology Pub Date : 2025-09-22 DOI: 10.1007/s00204-025-04191-0

Marie H Deventer, Christophe P Stove

{"title":"Outsmarting generic legislation: 4 years into the cat-and-mouse game of the synthetic cannabinoid receptor agonist market since the Chinese ban in 2021.","authors":"Marie H Deventer, Christophe P Stove","doi":"10.1007/s00204-025-04191-0","DOIUrl":"https://doi.org/10.1007/s00204-025-04191-0","url":null,"abstract":"The enactment of the generic ban on synthetic cannabinoid receptor agonists (SCRAs) in China in 2021 has significantly altered the international SCRA landscape, both in size and diversity. To circumvent the new legislation, covering 7 common SCRA scaffolds, manufacturers have employed various ban-evading strategies during the past 4 years, yielding numerous novel compounds with distinct properties and challenges. These strategies include introducing alternative core moieties, such as a oxoindolins (\"OXIZIDs\"), an oxopyridone (CH-FUBBMPDORA) and a 4-methyl benzoate (NMDMSB), as well as replacing the carboxamide linker with an acetamide (e.g., seen in ADB-FUBIATA). Additional approaches involve modifying conventional core structures by switching tail group positions (e.g., pyrazoles 5F-3,5-AB-PFUPPYCA and 3,5-ADB-4en-PFUPPYCA), or removing/adding substitutions (e.g., tail-less SCRAs like ADB-INACA and brominated SCRAs like ADB-5'Br-BUTINACA, respectively). Furthermore, a concerning 'do-it-yourself' synthesis approach has emerged, enabling users or intermediate suppliers to easily generate banned, potent SCRAs themselves from ban-evading tail-less precursors, thereby obtaining renewed access to previously scheduled and potentially dangerous compounds. In addition to the proliferation of structurally novel, unknown substances, new ways to market readily existing (highly potent) SCRAs, continue to complicate analytical detection and risk assessment. This review explores the ban-evading strategies that have been observed between mid-2021 and mid-2025, along with a discussion on strategies for detection, identification, metabolic profiling, and pharmacological characterization of the SCRAs that have emerged as a result of this ban. Additionally, for some compounds that have not been pharmacologically characterized in literature, the first published data are presented here.","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genotoxic carcinogenicity of pyrrolizidine alkaloids: relevance of potency factors for the risk assessment. 吡咯利西啶类生物碱的遗传毒性致癌性：与风险评估相关的效价因素。

IF 6.9 2区医学

Archives of Toxicology Pub Date : 2025-09-19 DOI: 10.1007/s00204-025-04182-1

Benjamin Sachse, Stefanie Hessel-Pras, Bernd Schäfer

{"title":"Genotoxic carcinogenicity of pyrrolizidine alkaloids: relevance of potency factors for the risk assessment.","authors":"Benjamin Sachse, Stefanie Hessel-Pras, Bernd Schäfer","doi":"10.1007/s00204-025-04182-1","DOIUrl":"https://doi.org/10.1007/s00204-025-04182-1","url":null,"abstract":"Pyrrolizidine alkaloids represent a large group of substances synthesized as secondary plant metabolites. The subgroup of the 1,2-unsaturated pyrrolizidine alkaloids (PAs) can induce acute and chronic liver toxicity in humans and livestock, and many of them are considered to be genotoxic and carcinogenic. Currently, the risk assessment is based on carcinogenicity data for the relatively potent PA riddelliine, and on the assumption that all PAs, regardless of their chemical structure, have the same potency. However, results from in vitro and in vivo studies indicate that the severity of the effects depends on the alkaloids' structure and, thus, varies for different congeners. To align the concept of potency factors with risk assessment, we analysed the available studies and selected those that best reflect the human situation or mode of action, and that included riddelliine in their study design. Based on the selected studies, we used riddelliine as a reference point to calculate the relative potencies of the PAs also used in the corresponding study. Further, we propose conservatively derived relative potency factors for certain PA congeners and evaluated the impact when applying them to real food samples considering tea and food supplements as examples. Our evaluation demonstrates that the inclusion of relative potency factors for PAs has generally only a minor influence on the final risk assessment, especially when conservative factors are used. However, this approach may be of great importance in certain situations where the PA spectrum consists mainly of PAs with low potency, such as the monoester lycopsamine.","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145084943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0