Drug and Chemical Toxicology最新文献

Pubertal atrazine exposure promotes adipocyte hypertrophy and hepatic steatosis in adult mice on a high-fat diet. 青春期接触阿特拉津会促进高脂肪饮食的成年小鼠的脂肪细胞肥大和肝脏脂肪变性。

IF 2.1 4区医学

Drug and Chemical Toxicology Pub Date : 2025-07-18 DOI: 10.1080/01480545.2025.2534714

Jakeline Liara Teleken, Isabela Carolina Menoncin Conte, Gabriel Schorr, Larissa Glugoski, Laura Bergenthal, Jean Luca Alves, Viviane Nogaroto Vicari, Marcelo Ricardo Vicari, Rosane Aparecida Ribeiro, Maria Lúcia Bonfleur

{"title":"Pubertal atrazine exposure promotes adipocyte hypertrophy and hepatic steatosis in adult mice on a high-fat diet.","authors":"Jakeline Liara Teleken, Isabela Carolina Menoncin Conte, Gabriel Schorr, Larissa Glugoski, Laura Bergenthal, Jean Luca Alves, Viviane Nogaroto Vicari, Marcelo Ricardo Vicari, Rosane Aparecida Ribeiro, Maria Lúcia Bonfleur","doi":"10.1080/01480545.2025.2534714","DOIUrl":"https://doi.org/10.1080/01480545.2025.2534714","url":null,"abstract":"The herbicide atrazine (ATZ) has been implicated in metabolic disruptions. This study investigated the long-term consequences of pubertal ATZ-based herbicide exposure on the development of obesity in mice fed a high-fat diet (HFD) in adulthood. Male and female C57Bl/6 mice received ATZ (5 mg/kg) or water (control group) from postnatal day (PND) 30 to 60. Following puberty, all mice were fed a HFD for 90 days. Pubertal ATZ-based herbicide exposure increases food intake, specifically in male mice. While body weight, subcutaneous adiposity, and white adipose tissue (WAT) weights remained unchanged, ATZ-exposed male mice showed worsened adipocyte hypertrophy and upregulation of genes involved fat metabolism (Srebp-2, Ppar-γ, Cd36, and Adrp) in perigonadal WAT. Additionally, pubertal ATZ exposure exacerbated hepatic steatosis in both sexes, with increased ectopic fat accumulation in females correlating with increases in genes involved in fatty acid uptake and exportation (fatty acid transport protein 5 and microsomal triglyceride transfer protein). These findings provide new insights into the long-term metabolic consequences of pubertal exposure to ATZ, including exacerbated HFD-induced adiposity and hepatic steatosis. The observed sex-specific effects underscore the importance of considering pubertal windows of susceptibility to environmental disruptors and their potential impacts on adult health.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-13"},"PeriodicalIF":2.1,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658698","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}

引用次数: 0

Topiramate exacerbates liver damage: a study on NAFLD, nitrosative stress and apoptosis. 托吡酯加重肝损伤：NAFLD、亚硝化应激和细胞凋亡的研究。

IF 2.1 4区医学

Drug and Chemical Toxicology Pub Date : 2025-07-18 DOI: 10.1080/01480545.2025.2533252

Sevtap Kılınç, Pelin Şahin, Zeynep Yığman, Müşerref Şeyma Ceyhan, Ayşe Meltem Sevgili

{"title":"Topiramate exacerbates liver damage: a study on NAFLD, nitrosative stress and apoptosis.","authors":"Sevtap Kılınç, Pelin Şahin, Zeynep Yığman, Müşerref Şeyma Ceyhan, Ayşe Meltem Sevgili","doi":"10.1080/01480545.2025.2533252","DOIUrl":"https://doi.org/10.1080/01480545.2025.2533252","url":null,"abstract":"Nonalcoholic fatty liver disease (NAFLD) is a common comorbidity of obesity. Topiramate (TPM) is an anti-obesity drug. Previously, TPM showed oxidative effect to the liver. On the other hand, its effect on nitrosative stress, inflammation, and apoptosis in healthy and fatty livers remains unclear. Therefore, we aim to fill this gap. Twenty-four male Wistar albino rats were randomly assigned to four groups: Control, Diet, TPM, and Diet + TPM. The diet groups received a high-fat diet for six weeks to induce NAFLD. The TPM groups administered orally (100 mg/kg/d) for an additional 21 days. Rat livers were analyzed for NO, nitrotyrosine, TNF-α, IL-10, caspase 3 and 9, and cytochrome-c (Cyt-c). Liver sections were evaluated immunohistochemically for BAX and BCL-2 expressions. Caspase-3, Caspase-9, and Cyt-c levels were increased, and IL-10 levels were decreased in both the diet and TPM groups. When applied together, Co-administration of a high-fat diet and TPM further elevated Caspase-9 and Cyt-c levels in the Diet + TPM group. Although TNF-α levels were higher in both the diet and TPM groups, statistical significance was attained only in the diet + TPM group. TPM also increased NO and nitrotyrosine levels in both standard and high-fat diet groups. TPM causes liver tissue nitrosative stress, and increased apoptosis regardless of NAFLD. Due to the high occurrence of NAFLD in obese people, it is important to carefully evaluate using TPM as an anti-obesity medicine.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-9"},"PeriodicalIF":2.1,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658699","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}

引用次数: 0

Effects of tris(2-chloroethyl)phosphate on hyperuricemia revealed by network toxicology and in vitro experimental validation. 磷酸三酯（2-氯乙基）对高尿酸血症的网络毒理学研究及体外实验验证。

IF 2.1 4区医学

Drug and Chemical Toxicology Pub Date : 2025-07-11 DOI: 10.1080/01480545.2025.2529514

Yongxiao Huang, Caina Jiang, Fangyao Li, Xianli Ma

{"title":"Effects of tris(2-chloroethyl)phosphate on hyperuricemia revealed by network toxicology and in vitro experimental validation.","authors":"Yongxiao Huang, Caina Jiang, Fangyao Li, Xianli Ma","doi":"10.1080/01480545.2025.2529514","DOIUrl":"https://doi.org/10.1080/01480545.2025.2529514","url":null,"abstract":"As a commonly used flame retardant in numerous products, it is inevitable that tris(2-chloroethyl)phosphate (TCEP) is released into the surrounding environment during its use. This process gives rise to potential environmental concerns that must be addressed. In recent years, there has been significant interest in the role of TCEP in the development of hyperuricemia (HUA). However, the specific mechanisms by which TCEP contributes to this condition remain to be fully elucidated. In this study, we have employed a combination of network toxicology and in vitro experiments to investigate the potential effects of TCEP on HUA and its mechanism of action. Through systematic analysis of GeneCards, OMIM, Swiss Target Prediction, and CHEMBL databases, a total of 242 TCEP-induced HUA targets were identified. Utilizing the STRING and DAVID databases further elucidated the core targets and associated signaling pathways of TCEP in relation to HUA. The molecular docking assay results demonstrated that TCEP exhibits binding activity with the selected targets. In vitro, our findings revealed that TCEP exacerbates HUA by amplifying the inflammatory response and upregulating the mRNA expression levels of GLUT9 and URAT1. The present study provides a new perspective and theoretical basis for the in-depth understanding of the molecular mechanism of TCEP affecting HUA, and helps to further understand the pathogenesis of HUA and the role of environmental factors.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-12"},"PeriodicalIF":2.1,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607827","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}

引用次数: 0

Tadehaginoside improves liver fibrosis in mice by inhibiting the activation of hepatic stellate cells mediated by the molecular axis of miR-155/FOXO3. taddehaginoside通过抑制miR-155/FOXO3分子轴介导的肝星状细胞活化，改善小鼠肝纤维化。

IF 2.1 4区医学

Drug and Chemical Toxicology Pub Date : 2025-07-10 DOI: 10.1080/01480545.2025.2527178

Aicun Tang, Luying Wei, Jiayi Gao, Zheng Zhang, Bingyu Xia, Xin Li, Qiuyu Lu

{"title":"Tadehaginoside improves liver fibrosis in mice by inhibiting the activation of hepatic stellate cells mediated by the molecular axis of miR-155/FOXO3.","authors":"Aicun Tang, Luying Wei, Jiayi Gao, Zheng Zhang, Bingyu Xia, Xin Li, Qiuyu Lu","doi":"10.1080/01480545.2025.2527178","DOIUrl":"https://doi.org/10.1080/01480545.2025.2527178","url":null,"abstract":"To analyze tadehaginoside (TA) for its effect on liver fibrosis and the associated mechanism. Mice with CCl4-mediated liver fibrosis were administered TA treatment for 6 weeks. Histopathological alterations in liver tissues were evaluated, and serum markers of hepatic injury, as well as the hepatic profibrotic gene and protein levels were detected. Transforming growth factor-β1 (TGF-β1) was adopted for inducing LX-2 cells. Following a 24-h TA intervention, we assessed pro-fibrotic gene and protein activation, proliferation and levels of TGF-β1-activated LX-2 cells. miR-155 and FOXO3 expressions were quantified in mice liver tissues and cells. The targeting relation of miR-155 with FOXO3 was verified. After regulating miR-155 and FOXO3 expression, the function of TA in cell activation, proliferation, and collagen accumulation was evaluated. The results indicated that TA treatment markedly alleviated CCl4-mediated mouse liver injury, inhibited collagen fiber deposition, and downregulated the hepatic pro-fibrotic gene and protein levels. Additionally, TA treatment suppressed TGF-β1-induced cell activation and proliferation, thus significantly reducing pro-fibrotic marker levels within cells. Furthermore, treatment with TA down-regulated miR-155 and up-regulated FOXO3 within CCl4-induced liver tissues as well as TGF-β1-induced cells. However, miR-155 overexpression or FOXO3 silencing partially mitigated the inhibition of TA against TGF-β1-mediated activation, proliferation, and fibrosis in cells. In conclusion, TA inhibits the activation of hepatic stellate cell (HSC) via miR-155/FOXO3 axis, thereby exerting its anti-hepatic fibrosis effect.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-13"},"PeriodicalIF":2.1,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599699","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}

引用次数: 0

Computational design and evaluation of low-toxicity saquinavir analogues targeting the catalytic dyad and oxyanion-hole loop of SARS-CoV-2 Mpro: insights from ensemble docking, molecular dynamics, dynamic undocking, and ADMET analysis. 针对SARS-CoV-2 Mpro催化双极体和氧阴离子空穴环的低毒性沙奎那韦类似物的计算设计和评估：来自集合对接、分子动力学、动态解对接和ADMET分析的见解

IF 2.1 4区医学

Drug and Chemical Toxicology Pub Date : 2025-07-09 DOI: 10.1080/01480545.2025.2528850

Kranthi Kumar Konidala, Umadevi Bommu, Suneetha Yeguvapalli

{"title":"Computational design and evaluation of low-toxicity saquinavir analogues targeting the catalytic dyad and oxyanion-hole loop of SARS-CoV-2 Mpro: insights from ensemble docking, molecular dynamics, dynamic undocking, and ADMET analysis.","authors":"Kranthi Kumar Konidala, Umadevi Bommu, Suneetha Yeguvapalli","doi":"10.1080/01480545.2025.2528850","DOIUrl":"https://doi.org/10.1080/01480545.2025.2528850","url":null,"abstract":"A myriad of therapeutic candidates targeting SARS-CoV-2 have entered clinical trials; however, the ongoing challenges in SARS-CoV-2 drug discovery, such as adverse effects associated with some therapeutic candidates, necessitate continuous efforts to identify novel therapeutic targets and strategies. This study leverages integrated in silico approaches, encompassing ensemble docking, molecular dynamics (MD) simulations, dynamic unbinding (DUck), and ADMET predictions, to identify novel saquinavir-related antiviral inhibitors targeting the catalytic dyad and oxyanion-hole loop of the SARS-CoV-2 main protease (Mpro). From a library of 33 saquinavir-related analogs, ensemble docking identified three high-affinity ligands (ΔG ≤ -9.8 kcal/mol). Subsequent MD simulations revealed stable Mpro-ligand complexes and significant structural perturbations within the catalytic dyad (His41-Cys145, ΔDdyad >1.0 Å) and the oxyanion-hole (Gly143-Ser144-Cys145, Δθoxy >5°). DUck simulations elucidated a stepwise dissociation mechanism, identifying key hotspot residues critical for ligand binding. Compounds CHEMBL3706523 and CHEMBL3706524 emerged as promising candidates, exhibiting robust interactions and slower dissociation rates (WQB >6 kcal/mol). These ligands stabilized the receptor and induced conformational changes that may hinder substrate binding, suggesting a potential 'block cluster' mechanism for inhibition. Favorable ADMET profiles further support their potential as drug candidates with low mammalian toxicity. This study provides a strong foundation for experimental validation and the subsequent development of effective antiviral therapies against SARS-CoV-2.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-15"},"PeriodicalIF":2.1,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590682","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}

引用次数: 0

Heavy metal mixture induced hippocampal toxicity involve biometal accumulation, increase in oxidative stress, inflammation, and caspase-3 activation in rats via Nrf-2/HO-1/BDNF pathway. 重金属混合物通过Nrf-2/HO-1/BDNF通路诱导大鼠海马毒性涉及生物金属积累、氧化应激增加、炎症和caspase-3激活。

IF 2.1 4区医学

Drug and Chemical Toxicology Pub Date : 2025-07-08 DOI: 10.1080/01480545.2025.2525149

Baridoo Donatus Dooka, Chinna N Orish, Anthonet N Ezejiofor, Chidinma P Anyachor, Theresa C Umeji, Kpobari W Nkpaa, Cecilia N Obasi, Ana Cirovic, Aleksandar Cirovic, Orish E Orisakwe

{"title":"Heavy metal mixture induced hippocampal toxicity involve biometal accumulation, increase in oxidative stress, inflammation, and caspase-3 activation in rats via Nrf-2/HO-1/BDNF pathway.","authors":"Baridoo Donatus Dooka, Chinna N Orish, Anthonet N Ezejiofor, Chidinma P Anyachor, Theresa C Umeji, Kpobari W Nkpaa, Cecilia N Obasi, Ana Cirovic, Aleksandar Cirovic, Orish E Orisakwe","doi":"10.1080/01480545.2025.2525149","DOIUrl":"https://doi.org/10.1080/01480545.2025.2525149","url":null,"abstract":"Exposure to heavy metal mixtures HMM can elicit significant health risks due to their combined toxic effects. This study investigates the mechanisms of hippocampal toxicity associated with HMM exposure. Rats were exposed to lead (Pb) 20, aluminum (Al) 35 and manganese (Mn) 0.564 mg/kg body weight alone or in combination for 90 days. The rats exposed to Pb-Al-Mn mixture spent least time exploring the open arms and had longer latency to find the hidden platform than the control and individual metal exposure groups in the Elevated Plus Maze test. Bioaccumulation of Pb, Al and Mn in the hippocampus was measured, oxido-inflammatory, markers, caspase-3, Nrf-2, Aβ40, Aβ42, occludin, BDNF were evaluated. Al, Pb and Mn exposure individually significantly (p ≤ 0.05) decreased the hippocampal antioxidant enzymes activities, glutathione level and increased oxidative stress and neuroinflammation biomarkers. HMM significantly increased caspase-3, Nrf-2, Aβ40 and Aβ42 and significantly decreased occludin, BDNF, HO-1 when compared with the control. HMM significantly (p ≤ 0.05) exacerbated hippocampal in comparison to individual Al, Pb or Mn. HMM induced hippocampal toxicity via multiple targets, namely biometal accumulation, increase in oxidative stress, inflammation, and caspase-3 activation in rats via Nrf-2/HO-1/BDNF. All in all, this study has shown that exposure to Pb-Al-Mn tertiary mixture, even at lower doses than individual heavy metals, significantly amplified anxiety-like behavior in comparison to exposure to individual heavy metals, which were associated with the alternations in Nrf-2, HO-1, Aβ-40, Aβ-42, BDNF, occludin levels, COX-2 and Caspase-3 activities in the hippocampus.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-12"},"PeriodicalIF":2.1,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583394","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}

引用次数: 0

Acute and subacute toxicity of ethanol leaf extract of Urtica simensis Hochst. ex A. Rich in rats. 荨麻叶提取物的急性和亚急性毒性研究。富含老鼠。

IF 2.1 4区医学

Drug and Chemical Toxicology Pub Date : 2025-07-08 DOI: 10.1080/01480545.2025.2527176

Bickes Wube, Kaleab Asres, Worku Gemechu, Sileshi Degu, Yonas Girma, Girma Seyoum

{"title":"Acute and subacute toxicity of ethanol leaf extract of Urtica simensis Hochst. ex A. Rich in rats.","authors":"Bickes Wube, Kaleab Asres, Worku Gemechu, Sileshi Degu, Yonas Girma, Girma Seyoum","doi":"10.1080/01480545.2025.2527176","DOIUrl":"https://doi.org/10.1080/01480545.2025.2527176","url":null,"abstract":"Urtica simensis is a native nutraceutical herb in Ethiopia, but its safety of repeated oral intake has not been reported yet. This study aimed to evaluate acute and subacute toxicity of ethanol leaf extract of U. simensis in rats. The median lethal dose (LD₅。) was determined using OECD guideline 425. Sixty rats (30 males and 30 females) were assigned to six groups per OECD guideline 407. Groups I-III received 250, 500 and 1000 mg/kg of U. simensis ethanol leaf extract daily for 4 weeks, while Group IV received distilled water. The satellite 1000 mg/kg and satellite control groups were monitored for additional 2 weeks. Clinical signs, food intakes and body weights were recorded. After 4 weeks, rats were euthanized for organ weight, blood chemistry and histopathological evaluations. The results revealed that the LD₅。 exceeded 5 g/kg. No adverse effects were observed at 250 mg/kg. However, 1000 mg/kg dose caused significant weight gain in both male and female rats. Doses of 500 and 1000 mg/kg significantly elevated alanine aminotransferase in both sexes of rats. Male rats given 1000 mg/kg showed significantly increased serum creatinine, while females exhibited reduced hemoglobin. Some female rats treated with 1000 mg/kg had liver parenchymal necrosis, kidney glomerular distortion and spleen white pulp depletion. In conclusion, 500 and 1000 mg/kg of leaf extract caused significant weight gain, biochemical changes and histopathological alterations in the liver, kidney and spleen of some female rats. Therefore, caution should be exercised when considering repeated oral intake of U. simensis leaves.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-12"},"PeriodicalIF":2.1,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583393","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}

引用次数: 0

Single acute and repeated subacute toxicity evaluations of Annona atemoya leaf extract with in vitro anti-inflammatory potential. 对具有体外抗炎潜力的Annona atemoya叶提取物进行单次急性和多次亚急性毒性评估。

IF 2.1 4区医学

Drug and Chemical Toxicology Pub Date : 2025-07-01 Epub Date: 2024-10-03 DOI: 10.1080/01480545.2024.2407866

Eunjin Sohn, Yu Jin Kim, Hye-Sun Lim, Soo-Jin Jeong

{"title":"Single acute and repeated subacute toxicity evaluations of Annona atemoya leaf extract with in vitro anti-inflammatory potential.","authors":"Eunjin Sohn, Yu Jin Kim, Hye-Sun Lim, Soo-Jin Jeong","doi":"10.1080/01480545.2024.2407866","DOIUrl":"10.1080/01480545.2024.2407866","url":null,"abstract":"The nutraceutical and biological potential of Annona atemoya, a fruiting plant, has been reported. We and others have demonstrated that A. atemoya leaf extract (AAL) has various pharmacological properties, such as antioxidant, antimicrobial, and neuroprotective effects. However, knowledge about the safety and potential toxicity of AAL remains limited. We aimed to assess the potential toxicity of AAL using acute and repeated subacute oral toxicity tests in rats. In both acute and repeated subacute toxicity test, no AAL-related behavioral abnormalities or changes in mortality, food intake, body weight were observed up to a dosage of 2000 mg/kg, indicating that the median lethal dose of AAL is higher than 2000 mg/kg. In subacute toxicity tests, no significant changes in hematological and biochemical parameters, urinalysis results, and histopathological variables were observed. Therefore, the no-observed-adverse-effect level (NOAEL) of orally administered AAL was estimated to be 2000 mg/kg/day in male and female rats. We also examined the effect of AAL on the inflammatory reaction in lipopolysaccharide (LPS)-stimulated BV-2 cells. AAL treatment significantly inhibited the LPS-stimulated increases in the levels of nitric oxide (NO) and inflammatory cytokines, implying that AAL has an anti-inflammatory effect. Quality control analysis revealed that two marker compounds, rutin and isoquercitrin, were present at 27.570 and 4.322 mg/g, respectively, in a freeze-dried AAL sample and were completely eluted within 27 min. The extraction recovery was 99.47-103.80%, and the precision was ≤2.79%. Overall, these findings suggest the safety, anti-inflammatory activity, and standardization of AAL.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"864-875"},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364793","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}

引用次数: 0

Cardiotoxicity induced by xanthatin via activating apoptosis and ERS pathways in zebrafish. 黄嘌呤通过激活斑马鱼细胞凋亡和ERS通路诱导心脏毒性。

IF 2.1 4区医学

Drug and Chemical Toxicology Pub Date : 2025-07-01 Epub Date: 2025-03-24 DOI: 10.1080/01480545.2025.2481863

Lixin Feng, Liyan Xu, Jing Huang, Yuxin Wang, Qing Xia, Jin Meng, Rongchun Wang, Kechun Liu

{"title":"Cardiotoxicity induced by xanthatin via activating apoptosis and ERS pathways in zebrafish.","authors":"Lixin Feng, Liyan Xu, Jing Huang, Yuxin Wang, Qing Xia, Jin Meng, Rongchun Wang, Kechun Liu","doi":"10.1080/01480545.2025.2481863","DOIUrl":"10.1080/01480545.2025.2481863","url":null,"abstract":"Xanthatin, a sesquiterpene lactone compound, isolated from Chinese herb, Xanthium strumarium L, has various activities, including anti-inflammatory, anti-tumor, anti-ulcer effects. However, it has been less studied in terms of its toxicity, especially the potential toxicity on heart. This study is mainly aimed to assess the cardiotoxicity of xanthatin in vivo using zebrafish larva and in vitro using cardiomyocytes H9C2. The cardiotoxicity in zebrafish was assessed by the pericardial edema, blood flow dynamics, SV-BA distance, and sub-intestinal vein. The apoptosis was determined by AO staining, the blood red cell reduction and distribution was detected by O-dianisidine staining, histopathological evaluations were detected by HE staining. The anti-proliferative and pro-apoptotic activities in H9C2 cells were assessed by EdU staining and Hoechst 33342/PI double staining. The in vivo results showed that xanthatin caused cardiac malformations and dysfunctions, including decreased heart rate, reduced red blood cell count, hemodynamics, stroke volume, increased SV-BA distance and sub-intestinal vein congestion. Furthermore, apoptosis occurred in the heart of the zebrafish after xanthatin exposure. Additionally, cat, Mn-sod, chop, perk, and hspa5 related to oxidative stress and ERS also changed by xanthatin. Apoptotic genes caspase3 and caspase9 were also increased. Moreover, the in vitro results showed that xanthatin had proapoptotic and antiproliferative effects. To sum up, these results suggest that xanthatin has cardiotoxicity and the oxidative stress, ERS and apoptosis pathways are involved in the cardiotoxicity induced by xanthatin. This finding will be helpful for the better understanding of the potential cardiotoxicity of xanthatin and the underlying mechanism.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"806-817"},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691535","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}

引用次数: 0

Impact of graded doses of enrofloxacin on the safety and biological responses of Nile tilapia Oreochromis niloticus. 分级剂量恩诺沙星对尼罗罗非鱼（Oreochromis niloticus）安全性和生物反应的影响。

IF 2.1 4区医学

Drug and Chemical Toxicology Pub Date : 2025-07-01 Epub Date: 2024-09-25 DOI: 10.1080/01480545.2024.2405831

Ratnapriya Das, Thangapalam Jawahar Abraham, Arya Sen, Ravindran Rajisha, Ranjit Kumar Nadella, Niladri Sekhar Chatterjee, Prasanna Kumar Patil

{"title":"Impact of graded doses of enrofloxacin on the safety and biological responses of Nile tilapia Oreochromis niloticus.","authors":"Ratnapriya Das, Thangapalam Jawahar Abraham, Arya Sen, Ravindran Rajisha, Ranjit Kumar Nadella, Niladri Sekhar Chatterjee, Prasanna Kumar Patil","doi":"10.1080/01480545.2024.2405831","DOIUrl":"10.1080/01480545.2024.2405831","url":null,"abstract":"The cultivation of tilapias, the third most farmed fish group globally, has been rapidly growing, especially in Southeast Asia. This surge in tilapia farming intensification has led to increased use of antibiotics to control bacterial diseases. This study investigated the safety implications of administering graded doses of enrofloxacin (ENF) at 0 (control), 10, 30, 50 and 100 mg/kg biomass/day orally to Oreochromis niloticus. The 43-day study comprised 7 days of pre-dosing, 15 days of ENF-dosing, and a 21-day recovery period with a periodical assessment of the biological responses of fish. The results revealed that the overdosed groups experienced up to 21% reduction in feed consumption, 11% mortalities, and adverse impacts on hematology, including a decrease in erythrocytes, and monocytes and an increase in leukocytes, thrombocytes, lymphocytes, and neutrophils. Haematological indices like mean corpuscular volume and mean corpuscular hemoglobin decreased, while mean corpuscular hemoglobin concentration increased. The plasma biochemical parameters including glucose and liver and kidney enzymes unveiled a significant dose- and time-dependent increase, while calcium and chloride levels decreased. Erythrocytes displayed several erythrocyte cellular and nuclear abnormalities. The frequency of micronucleus increased with dose and time, suggesting potential genotoxicity of ENF. Additionally, a dose-dependent increase in residues in the tissues with the highest accumulation in muscle was documented. Nevertheless, the recovery of the measured parameters upon dose termination indicated that the ENF-induced alterations are reversible. The study affirmed the safety of ENF at the recommended dose (10 mg) in O. niloticus and their adoptive responses to higher doses.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"784-796"},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343600","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}

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