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A membrane-rupturing protein similar to SIGLEC12 might be involved in sodium arsenite-induced lytic cardiomyocyte death and myocardial necroinflammation. 一种类似SIGLEC12的破膜蛋白可能参与亚砷酸钠诱导的溶性心肌细胞死亡和心肌坏死炎症。
IF 2.2 4区 医学
Drug and Chemical Toxicology Pub Date : 2026-09-01 Epub Date: 2026-08-06 DOI: 10.1080/01480545.2026.2711647
Caglar Berkel
{"title":"A membrane-rupturing protein similar to SIGLEC12 might be involved in sodium arsenite-induced lytic cardiomyocyte death and myocardial necroinflammation.","authors":"Caglar Berkel","doi":"10.1080/01480545.2026.2711647","DOIUrl":"10.1080/01480545.2026.2711647","url":null,"abstract":"","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1005-1007"},"PeriodicalIF":2.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148683884","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
Xenobiotic modalities impacting the thyroid 3H framework of hormonogenesis, homeostasis, and human health. 影响激素生成、体内平衡和人类健康的甲状腺3H框架的异种生物模式。
IF 2.2 4区 医学
Drug and Chemical Toxicology Pub Date : 2026-09-01 Epub Date: 2026-01-08 DOI: 10.1080/01480545.2025.2606102
Abhishek Tater, Bharath Basavapattana Rudresh, Santosh L Gaonkar
{"title":"Xenobiotic modalities impacting the thyroid 3H framework of hormonogenesis, homeostasis, and human health.","authors":"Abhishek Tater, Bharath Basavapattana Rudresh, Santosh L Gaonkar","doi":"10.1080/01480545.2025.2606102","DOIUrl":"10.1080/01480545.2025.2606102","url":null,"abstract":"<p><p>The thyroid gland is a central endocrine organ regulating growth, metabolism, and energy balance, and is increasingly vulnerable to interference by diverse xenobiotic compounds from pharmaceuticals, environmental pollutants, diet, and consumer products. This review introduces a thyroid '3H' framework - hormonogenesis, homeostasis, and human health - to integrate current understanding of how thyroid endocrine-disrupting chemicals (Thy-EDCs) perturb thyroid physiology and the hypothalamic-pituitary-thyroid axis. A systematic literature search was conducted using PubMed, Scopus, and Web of Science, supplemented by reference screening to ensure comprehensive coverage of mechanistic and toxicological evidence. The synthesis indicates that various exogenous compounds - including tyrosine kinase inhibitors, immune checkpoint inhibitors, heavy metals, industrial endocrine disruptors, and certain dietary phytochemicals - affect thyroid function through multiple molecular initiating events. These include inhibition of thyroperoxidase, disruption of iodine uptake and organification, altered deiodinase activity, modulation of thyroid hormone receptor signaling, and immune-mediated effects on thyroid tissue. Such perturbations lead to abnormalities in hormone synthesis, metabolism, and systemic hormone homeostasis. Emerging structure-activity relationship (SAR) and computational modeling approaches provide further insight into how specific chemical features determine thyroid-disruptive potential, supporting the advancement of predictive toxicology and risk assessment. The novelty of this review lies in its integrated 3H perspective, linking physiological, molecular, immunological, and toxicological dimensions of thyroid disruption. This conceptual framework supports improved diagnosis of thyroid dysfunction, promotes safer chemical and drug design, and informs regulatory strategies aimed at protecting endocrine health.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1247-1265"},"PeriodicalIF":2.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145932673","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
Evaluation of therapeutic effects of royal jelly versus Nigella sativa oil on some brain areas affected by acute methanol poisoning in rats. 蜂王浆与黑油对急性甲醇中毒大鼠部分脑区治疗效果的比较。
IF 2.2 4区 医学
Drug and Chemical Toxicology Pub Date : 2026-09-01 Epub Date: 2025-11-17 DOI: 10.1080/01480545.2025.2586135
Yasmien Morsy, Marwa Shahin, Eman Draz, Naglaa Sarhan, Ahmed Hashem
{"title":"Evaluation of therapeutic effects of royal jelly versus <i>Nigella sativa</i> oil on some brain areas affected by acute methanol poisoning in rats.","authors":"Yasmien Morsy, Marwa Shahin, Eman Draz, Naglaa Sarhan, Ahmed Hashem","doi":"10.1080/01480545.2025.2586135","DOIUrl":"10.1080/01480545.2025.2586135","url":null,"abstract":"<p><p>Methanol (CH<sub>3</sub>OH) is one of the toxic alcohols that has high morbidity and mortality. It causes lipid peroxidation and oxidative stress. Antioxidants and neuroprotective agents could have therapeutic roles in case of methanol exposure. The aim of this research was to assess the therapeutic impact of royal jelly (RJ) versus <i>Nigella sativa</i> oil (NS) on brain areas affected by acute methanol poisoning in rats. This research was performed on 60 adult male albino rats that were randomly assigned to four groups: the negative control group (I), the positive control group (II), the methanol-intoxicated group (III), and the methanol and adjuvant treatment treated group (IV) which were categorized into two subgroups: the methanol and RJ treated group (IV a) and the methanol and NS treated group (IV b). After two weeks, the blood samples were obtained to determine the total antioxidant capacity (TAC). The frontal cortex, cerebellum, and hippocampus were excised and subjected to histopathological and transmission electron microscopic examination. Acute methanol poisoning induced oxidative stress, indicated by a significant reduction of TAC and marked degenerative changes in nerve cells and nerve fibers. Moreover, the administration of RJ and NS six hours after induction of acute methanol poisoning showed an increase in TAC compared to group III and a non-significant reduction compared to group II, with marked improvement and restoration of the normal brain architecture. Therefore, RJ and NS are effective in reducing the oxidative stress induced by acute methanol poisoning.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1170-1183"},"PeriodicalIF":2.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145539612","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
The phytoestrogen equol protects mice against acetaminophen hepatotoxicity. 植物雌激素雌马酚对小鼠对乙酰氨基酚肝毒性有保护作用。
IF 2.2 4区 医学
Drug and Chemical Toxicology Pub Date : 2026-09-01 Epub Date: 2026-03-09 DOI: 10.1080/01480545.2025.2575075
Yasuhiro Masubuchi, Kazuya Tachibana, Nana Niihori
{"title":"The phytoestrogen equol protects mice against acetaminophen hepatotoxicity.","authors":"Yasuhiro Masubuchi, Kazuya Tachibana, Nana Niihori","doi":"10.1080/01480545.2025.2575075","DOIUrl":"10.1080/01480545.2025.2575075","url":null,"abstract":"<p><p>Female mice have been resistant to acetaminophen (APAP)-induced liver injury, demonstrating that endogenous estrogens provide hepatoprotection, and it is expected that exogenous estrogens may also provide a similar effect. In the present study, we investigated the protective effects of the phytoestrogens equol and genistein against APAP-induced liver injury. Male CD-1 mice were intraperitoneally injected with APAP. Equol or genistein was administered 16 h prior and co-administered with APAP. The blood and liver samples were subjected to evaluation of hepatotoxicity, liver GSH levels and hepatic expression of inflammatory mediators. Phytoestrogen treatment effectively prevented APAP hepatotoxicity. Neither affected the early depletion of hepatic glutathione (GSH) caused by APAP, indicating that they did not affect the generation of <i>N</i>-acetyl-<i>p</i>-benzoquinone imine from APAP. This result was supported by <i>in vitro</i> studies with microsomes, which presented that both phytoestrogens inhibited CYP2E1 and CYP1A2 activities; however, high concentrations of these compounds were required. In contrast, genistein and, to a lesser extent, equol promoted the recovery of GSH after the depletion. Hepatic interleukin-6 expression was increased by after APAP administration, and the increase was suppressed by equol and genistein treatment, potentially contributing to hepatoprotection. The phytoestrogens equol and genistein protect mice from APAP hepatotoxicity, possibly by suppressing liver inflammation through their estrogen-dependent mechanisms.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1032-1037"},"PeriodicalIF":2.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147389835","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
Lipid profile, toxicity, and antioxidant potential of flavonoid-rich babassu mesocarp extract after simulated human digestion. 模拟人体消化后富含类黄酮的巴巴苏中果皮提取物的脂质特征、毒性和抗氧化潜力。
IF 2.2 4区 医学
Drug and Chemical Toxicology Pub Date : 2026-09-01 Epub Date: 2025-12-16 DOI: 10.1080/01480545.2025.2581706
N Debia, A M Nunes, M L L B do Nascimento, E R S Neta, M S R Rocha, S G Lima, J M C Sousa, P Falagan-Lotsch
{"title":"Lipid profile, toxicity, and antioxidant potential of flavonoid-rich babassu mesocarp extract after simulated human digestion.","authors":"N Debia, A M Nunes, M L L B do Nascimento, E R S Neta, M S R Rocha, S G Lima, J M C Sousa, P Falagan-Lotsch","doi":"10.1080/01480545.2025.2581706","DOIUrl":"10.1080/01480545.2025.2581706","url":null,"abstract":"<p><p>The babassu (<i>Attalea speciosa</i> Mart. ex Spreng, syn. Orbignya phalerata Mart), native to Brazil, is valued for its medicinal properties. Babassu mesocarp flour has attracted interest for its high flavonoid content. Given the antioxidant effects of flavonoids-and the potential for pro-oxidant or hepatotoxic effects at high doses, and their interactions with other phytochemicals, this study assessed the toxicity and antioxidant activity of a well- characterized hydroethanolic babassu mesocarp extract following <i>in vitro</i> human gastrointestinal digestion to mimic physiological conditions. Additionally, this study offered a physicochemical characterization of the extract's lipid derivatives. Beyond flavonoids, the crude extract exhibited a complex lipid profile, mainly phytosterols. The digested extract (DBME) showed reduced particle size, and it was not cytotoxic to human liver (HepG2) cells. Strong antioxidant effects were observed in HepG2 under oxidative stress conditions, even at low doses. DBME lowered reactive oxygen species (ROS), restored mitochondrial function, and downregulated ROS-induced antioxidant gene expression, highlighting its protective role against oxidative damage and mitochondrial dysfunction. Our findings reinforce the therapeutic potential of babassu mesocarp extracts as antioxidant agents and support their future consideration as an ingredient in functional foods or dietary supplements, based on the potential synergistic action between flavonoids and phytosterols identified within the same food matrix.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1184-1196"},"PeriodicalIF":2.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145766863","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
Synergistic hepatoprotection by supplementing Saussurea costus (falc.) lipsch and Glycyrrhiza glabra L. in combination against Diethylnitrosamine-induced liver damage in rats. 雪莲、甘草联合对二乙基亚硝胺所致大鼠肝损伤的协同保护作用。
IF 2.2 4区 医学
Drug and Chemical Toxicology Pub Date : 2026-09-01 Epub Date: 2025-10-16 DOI: 10.1080/01480545.2025.2564431
Bisen Harsh, Rakesh Kumar, R K Asrani, Joshi Gaurav Santoshrao, Ekta Bisht, Shreya Katoch, Vinesh Sharma, Vikarm Patial, Adarsh Kumar
{"title":"Synergistic hepatoprotection by supplementing <i>Saussurea costus</i> (falc.) lipsch and <i>Glycyrrhiza glabra</i> L. in combination against Diethylnitrosamine-induced liver damage in rats.","authors":"Bisen Harsh, Rakesh Kumar, R K Asrani, Joshi Gaurav Santoshrao, Ekta Bisht, Shreya Katoch, Vinesh Sharma, Vikarm Patial, Adarsh Kumar","doi":"10.1080/01480545.2025.2564431","DOIUrl":"10.1080/01480545.2025.2564431","url":null,"abstract":"<p><p>This study aims to evaluate the hepatoprotective effects of combined Saussurea costus and Glycyrrhiza glabra extracts against diethylnitrosamine (DEN)-induced hepatic damage in rats. In the present investigation, the <i>in vivo</i> experimental study involved forty-two male Albino Wistar rats allocated into seven groups of six rats in each. Group I served as the vehicle control (10% DMSO) and Group II was administered DEN at a concentration of 0.01% in drinking water. Group III received both DEN and silymarin at 25 mg/kg bw. Groups IV and V were treated with individual extracts of <i>S. costus</i> and <i>G. glabra</i> at 250 mg/kg bw, respectively. Groups VI and VII received combined lower (LDC) and higher doses (HDC) of both plant extracts i.e., 125 mg/kg bw and 250 mg/kg bw, respectively. The ultrasonographic evaluation revealed a significant increase in hepatic echotexture in the positive control group compared to ameliorative groups provided with various plant extract combinations depicting minimal changes comparable to the standard control i.e., rats provided with silymarin. Serum levels of ALT, AST, ALB, creatinine, and LPO indicating liver damage were diminished in the various treatment groups compared to group II receiving DEN only.</p><p><p>Therefore, the current study concluded that the higher combined dosage of the root extracts of <i>S. costus</i> and <i>G. glabra</i> i.e., 250 mg/kg bw each, demonstrated the hepatoprotective effect against DEN-induced liver damage in the rat model.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1008-1020"},"PeriodicalIF":2.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145298917","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
Renoprotective effect of roflumilast against amikacin- induced nephrotoxicity: upregulation of Nrf2 signaling, inhibition of cytokines, and renal apoptosis. 罗氟司特对阿米卡星所致肾毒性的肾保护作用:Nrf2信号的上调、细胞因子的抑制和肾细胞凋亡。
IF 2.2 4区 医学
Drug and Chemical Toxicology Pub Date : 2026-09-01 Epub Date: 2026-06-22 DOI: 10.1080/01480545.2026.2657439
Mona A Abdel-Kareem, Medhat Taha, Magda E Ahmed, Reham Mohammed Atef, Sanad S El-Kholy, Noura H Zidane, Mohammed E Elmitwalli, Tourki A S Baokbah, Ibrahim El-Shenbaby, Kareem Gomaa Al Sayed Ali, Noha M Halloull, Omnia Hassan Megahed, Rehab Abd El Azeem Esa, Ahmed Nahed Zaky Mohamed, Emadeldeen Hussin
{"title":"Renoprotective effect of roflumilast against amikacin- induced nephrotoxicity: upregulation of Nrf2 signaling, inhibition of cytokines, and renal apoptosis.","authors":"Mona A Abdel-Kareem, Medhat Taha, Magda E Ahmed, Reham Mohammed Atef, Sanad S El-Kholy, Noura H Zidane, Mohammed E Elmitwalli, Tourki A S Baokbah, Ibrahim El-Shenbaby, Kareem Gomaa Al Sayed Ali, Noha M Halloull, Omnia Hassan Megahed, Rehab Abd El Azeem Esa, Ahmed Nahed Zaky Mohamed, Emadeldeen Hussin","doi":"10.1080/01480545.2026.2657439","DOIUrl":"10.1080/01480545.2026.2657439","url":null,"abstract":"<p><p>ABSTARCTAmikacin (AK), a potent aminoglycoside antibiotic, is known to induce nephrotoxicity. This study evaluated the renoprotective effects of ROF, a selective PDE4 inhibitor, against AK-induced renal injury in Wistar rats. Forty male rats were divided into four groups (n = 10): Control (saline), ROF-only (1.5 mg/kg/day orally for 6 days), AK-only (single intraperitoneal injection of 1.2 g/kg on day 3), and AK+ROF (co-treatment). Renal function was assessed via serum creatinine and BUN. Oxidative stress was evaluated by measuring MDA and the antioxidants GSH, SOD, and CAT. The expression of key proteins in the Nrf2/HO-1, NF-κB, and apoptotic pathways was analyzed using ELISA and IHC. Kidney histopathology was examined using H&E, PAS, and Masson's trichrome staining. AK administration significantly elevated serum creatinine and BUN levels, increased lipid peroxidation, and suppressed antioxidant enzymes (SOD, CAT, and GSH). It also upregulated NF-κB along with TNF-α, IL-1β, and IL-6, and enhanced apoptotic markers (caspase-3, Bax) while reducing Bcl-2 expression. Histopathological analysis revealed severe tubular degeneration and inflammatory infiltration in the AK group. The most prominent finding was that ROF co-treatment robustly activated the Nrf2/HO-1 antioxidant pathway, leading to a comprehensive protective effect. ROF significantly ameliorated renal dysfunction, restored antioxidant enzyme activities, and reduced lipid peroxidation. It concurrently suppressed the NF-κB inflammatory cascade and modulated apoptotic signaling. These biochemical improvements were corroborated by marked histopathological recovery. In conclusion, ROF demonstrated potent renoprotection against AK-induced injury primarily through Nrf2/HO-1 pathway activation, which underpinned its synergistic antioxidant, anti-inflammatory, and anti-apoptotic actions, supporting its potential as a therapeutic strategy to mitigate aminoglycoside nephrotoxicity.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1225-1235"},"PeriodicalIF":2.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148293829","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
Phytochemical characterization and cytogenotoxic activity of leaves of Centratherum punctatum Cass. 刺心草叶片的植物化学特性及细胞毒活性研究。
IF 2.2 4区 医学
Drug and Chemical Toxicology Pub Date : 2026-09-01 Epub Date: 2026-01-26 DOI: 10.1080/01480545.2025.2586137
Ana Karla Araújo Silva, Yasmin Lorene de Alvarenga Araujo, Helena Albuquerque Barbosa, Geicylanne da Silva Marques Belfort, Lívia Lorena Araújo Silva, Maria das Dores Alves Oliveira, Jurandy do Nascimento Silva, Nerilson Marques Lima, Joaquim Soares da Costa Júnior, Wildson Max Barbosa da Silva, Francielle Alline Martins, Francisco Artur E Silva Filho, Sâmya Danielle Lima de Freitas, Pedro Marcos de Almeida
{"title":"Phytochemical characterization and cytogenotoxic activity of leaves of <i>Centratherum punctatum</i> Cass.","authors":"Ana Karla Araújo Silva, Yasmin Lorene de Alvarenga Araujo, Helena Albuquerque Barbosa, Geicylanne da Silva Marques Belfort, Lívia Lorena Araújo Silva, Maria das Dores Alves Oliveira, Jurandy do Nascimento Silva, Nerilson Marques Lima, Joaquim Soares da Costa Júnior, Wildson Max Barbosa da Silva, Francielle Alline Martins, Francisco Artur E Silva Filho, Sâmya Danielle Lima de Freitas, Pedro Marcos de Almeida","doi":"10.1080/01480545.2025.2586137","DOIUrl":"10.1080/01480545.2025.2586137","url":null,"abstract":"<p><p><i>Centratherum punctatum</i> (Asteraceae), known as Brazilian bachelor's button, is used in folk medicine to treat liver problems, intestinal discomfort, and ulcers. The study aims to characterize the ethanolic extract (EE) of <i>C. punctatum</i> leaves, evaluate its antioxidant activity, and assess its cytogenotoxic and chemoprotective effects in <i>Allium cepa</i> and <i>Drosophila melanogaster</i> cells. The EE was characterized by qualitative phytochemical prospecting, TLC, ESI-IT/MS<sup>n</sup>, HPLC-PDA, and isolation by column chromatography. Antioxidant activity (DPPH and ABTS) and total phenol content (TPC) were quantified. Cytogenotoxicity and the protective effect of EE were evaluated in the <i>A. cepa</i> and the somatic mutation and recombination test (SMART) bioassays at concentrations of 3.9; 15.6; 62.5 and 250 µg/mL. The phytochemical prospecting of EE revealed the presence of tannins, saponins, flavanones, alkaloids, terpenes, and flavonoids. ESI-IT/MS<sup>n</sup> identified 15 compounds, HPLC-PDA also confirmed the same classes of metabolites, and the isolate was the triterpene acetyl aleuritolic acid. The result of DPPH, ABTS, and TPC was 142.10 ± 2.15 µg/mL; 623.94 ± 38.38 mM Trolox/g, and 77.78 ± 1.19 mg EAG/g, respectively. In <i>A. cepa</i> and SMART, none of the EE concentrations were cytogenotoxic. EE showed a protective effect (pre, simultaneous, and post-treatments) against methyl methanesulfonate damage at all concentrations in <i>A. cepa</i> and antigenotoxic activity (simultaneous) in SMART at 15.6; 62.5, and 250 µg/mL against doxorubicin damage. The findings of the present study demonstrate that <i>C. punctatum</i> is a promising source of compounds with antioxidant and chemoprotective properties.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1197-1212"},"PeriodicalIF":2.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046288","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
Metformin attenuates valproic acid-induced developmental cardiotoxicity through activation of the AMPK/PGC-1α axis and restoration of mitochondrial and redox homeostasis in zebrafish embryos. 二甲双胍通过激活AMPK/PGC-1α轴,恢复斑马鱼胚胎线粒体和氧化还原稳态,减轻丙戊酸诱导的发育性心脏毒性。
IF 2.2 4区 医学
Drug and Chemical Toxicology Pub Date : 2026-09-01 Epub Date: 2026-06-08 DOI: 10.1080/01480545.2026.2684476
Ünsal Veli Üstündağ, Fümet Duygu Üstündağ, Neşe Ayşit
{"title":"Metformin attenuates valproic acid-induced developmental cardiotoxicity through activation of the AMPK/PGC-1α axis and restoration of mitochondrial and redox homeostasis in zebrafish embryos.","authors":"Ünsal Veli Üstündağ, Fümet Duygu Üstündağ, Neşe Ayşit","doi":"10.1080/01480545.2026.2684476","DOIUrl":"10.1080/01480545.2026.2684476","url":null,"abstract":"<p><p>Prenatal valproic acid (VPA) exposure is strongly linked to developmental cardiotoxicity, yet no targeted pharmacological countermeasure exists. Converging mechanistic evidence indicates that VPA cardiotoxicity centers on AMPK/PGC-1α suppression, positioning the AMPK activator metformin (MET) as a rational candidate for <i>in vivo</i> protection. We examined MET's protective effects against VPA-induced developmental cardiotoxicity in zebrafish embryos. Embryos were randomly allocated to four groups (Control, VPA 0.1 mM, MET 10 mM, VPA + MET) immediately after fertilization and chronically exposed until 96 hpf. Oxidative stress biomarkers (MDA, NO, SOD, GSH) and the expression of cardiac (<i>nkx2.5, vmhc, amhc</i>), AMPK (<i>prkaa2, acaca</i>), and mitochondrial/energy-related genes (<i>ppargc1a, cpt1b, pck1, atp5pb, mt-nd1</i>) were quantified. Compared with controls, VPA reduced <i>nkx2.5</i> (p < 0.01) and elevated <i>amhc</i> (p < 0.05), triggered pericardial edema (p < 0.0001), suppressed <i>prkaa2, ppargc1a</i>, and <i>atp5pb</i> (p < 0.05, p < 0.001, and p < 0.0001, respectively), upregulated <i>acaca</i> (p < 0.0001), increased MDA and NO (p < 0.0001), and lowered SOD and GSH (p < 0.0001 and p < 0.001, respectively). Relative to the VPA group, MET co-treatment restored <i>nkx2.5</i> expression (p < 0.001), attenuated pericardial edema (p < 0.0001), increased <i>prkaa2</i> (p < 0.05), <i>ppargc1a</i> (p < 0.01), and <i>atp5pb</i> (p < 0.0001), suppressed <i>acaca</i> (p < 0.0001), and normalized MDA (p < 0.05), NO (p < 0.0001), SOD, and GSH (both p < 0.0001). The restoration of <i>prkaa2/ppargc1a</i>, mitochondrial, and antioxidant capacity by MET suggests that the AMPK/PGC-1α axis may serve as a central target in VPA cardiotoxicity.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1114-1124"},"PeriodicalIF":2.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148204321","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
Quinestrol nanoparticle-based formulation for long-term oral contraception against the wild female rats, Bandicota bengalensis. 基于喹雌酚纳米颗粒的对野生雌性大鼠长期口服避孕药的研究。
IF 2.2 4区 医学
Drug and Chemical Toxicology Pub Date : 2026-09-01 Epub Date: 2025-11-17 DOI: 10.1080/01480545.2025.2585142
Dimple Mandla, Neena Singla, Anu Kalia, Varinder Uppal
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