Toxicology and applied pharmacology最新文献

{"title":"Thiostrepton suppresses colorectal cancer progression through reactive oxygen species related endoplasmic reticulum stress","authors":"Zhexuan Li ,&nbsp;Juan Nie ,&nbsp;Runyu Zhou ,&nbsp;Hui Huang ,&nbsp;Xuemei Li ,&nbsp;Li Wang ,&nbsp;Lin Lv ,&nbsp;Sichong Ren ,&nbsp;Ming Zhao","doi":"10.1016/j.taap.2024.117221","DOIUrl":"10.1016/j.taap.2024.117221","url":null,"abstract":"<div><div>Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. Due to the poor therapeutic efficacy of CRC treatments and poor prognosis of the disease, effective treatment strategies are urgently needed. As long-term proteotoxic stress is a major cause of cell death, agents that induce proteotoxic stress offer a promising strategy for cancer intervention. Thiostrepton is a natural antibiotic derived from the <em>Streptomyces</em> genus. In the present study, we found that thiostrepton triggered apoptosis, reduced the migration of CRC cells, and inhibited xenograft tumour growth <em>in vivo</em>. Mechanistically, thiostrepton reduced proteasome activity; induced the aggregation of ubiquitinated proteins; caused endoplasmic reticulum (ER) stress, which was characterized by increased protein levels of GRP78, ATF4, P-eIF2α, and CHOP and cytosolic calcium release; and ultimately resulted in cell death. Thiostrepton-related changes in cell survival and cell migration, as well as mechanistical processes, were almost completely reversed by treatment with the antioxidant <em>N</em>-acetylcysteine (NAC), suggesting that the mechanism is dependent on reactive oxygen species (ROS). These results demonstrated that thiostrepton induced apoptosis and inhibited migration through ROS-induced ER stress and proteotoxic stress in colorectal cancer.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"495 ","pages":"Article 117221"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiac inotropy and cardiac calcium sensitization of PanLN800(-Forte), a cationic heptamethine indocyanine fluorescent contrast agent for intraoperative pan lymph node imaging","authors":"Robin A. Faber ,&nbsp;Victor M. Baart ,&nbsp;Mark W. Bordo ,&nbsp;Taryn L. March ,&nbsp;Adrianus R.P.M. Valentijn ,&nbsp;Stefan Harmsen ,&nbsp;Martin Pool ,&nbsp;Jacobus Burggraaf ,&nbsp;John V. Frangioni ,&nbsp;Alexander L. Vahrmeijer","doi":"10.1016/j.taap.2024.117222","DOIUrl":"10.1016/j.taap.2024.117222","url":null,"abstract":"<div><h3>Introduction</h3><div>Accurate staging of malignancies often requires comprehensive evaluation of lymph nodes. However, finding these lymph nodes during oncological surgery is a daunting and time-consuming task, which increases the risk of missed lymph nodes and complications. Near-infrared (NIR) fluorescence imaging with the experimental fluorescent contrast agent PanLN800(-Forte) could provide real-time identification of lymph nodes and may solve this longstanding problem. In the current study we performed the preclinical toxicology evaluation of PanLN800(-Forte) towards its clinical translation for intraoperative pan lymph node imaging in thoracic surgery.</div></div><div><h3>Methods</h3><div>A single extended dose toxicology study was conducted to determine the safety and potential toxicity of PanLN800(-Forte) after administration of a single intravenous dose to Wistar Han rats. The study included a control group and two treatment groups (5.0 mg/kg and 15.0 mg/kg PanLN800(-Forte)), each consisting of 10 male and 10 female rats. Experimental endpoints included moribundity/mortality, clinical signs, body weights, body weight gains, clinical pathology, toxicity, and gross necropsy observations.</div></div><div><h3>Results</h3><div>Unexpected acute mortality was observed after administration of 5.0 mg/kg PanLN800(-Forte) to rats. No clear cause of sudden death was found after gross necropsy and pathology observations. To understand the mechanism of toxicity of PanLN800(-Forte), several additional tests were performed. By elimination, acute cardiac toxicity appears to be the cause of acute mortality in rats, in which PanLN800(-Forte) was found to be a potent inotrope acting as a cardiac calcium sensitizer.</div></div><div><h3>Conclusion</h3><div>PanLN800(-Forte) is not a viable fluorescent contrast agent for lymph node imaging in surgery because of cardiac calcium sensitization but may be a novel treatment for heart failure.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"495 ","pages":"Article 117222"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T-2 toxin triggers immunotoxic effects in goats by inducing ferroptosis and neutrophil extracellular traps","authors":"Jing Huang ,&nbsp;Kaifeng He ,&nbsp;Xin Guo ,&nbsp;Jiaxuan Wang ,&nbsp;Han Hu ,&nbsp;Xuhui Zhang ,&nbsp;Na Guo ,&nbsp;Yiwen Wang ,&nbsp;Wenlong Huang ,&nbsp;Rongsheng Huang ,&nbsp;Tingting Liu ,&nbsp;Xi Jiang ,&nbsp;Deizhi Zhang ,&nbsp;Qianyong Li ,&nbsp;Zhengkai Wei","doi":"10.1016/j.taap.2025.117232","DOIUrl":"10.1016/j.taap.2025.117232","url":null,"abstract":"<div><div>T-2 toxin, a prevalent mycotoxin, represents a notable global public health risk. Neutrophil extracellular traps (NETs) and ferroptosis are involved in a variety of pathophysiological processes and are implicated in goat immunity. However, the impact of T-2 toxin on NETs release, ferroptosis, and their interplay have not been previously documented. In this study, neutrophils were stimulated with T-2 toxin for 4 h. The structure and mechanism of NETs were analyzed using immunofluorescence and Pico Green staining. The expressions of glutathione peroxidase 4 (GPX4) and ferritin (FT) was quantified by qRT-PCR and western blotting. The levels of ROS and lipid ROS were assessed using DCFH-DA and C11 BODIPY 581/591 probes, and cellular mitochondria Fe²⁺ were detected by using Mito-FerroGreen probe. Inhibitors were utilized to explore the interaction between these two processes. The results confirmed that the T-2 toxin stimulated the NETs production, characterized by a structure co-modified by citrullinated histones (citH3), neutrophil elastase (NE) and DNA. Notably, significant inhibition of NETs production by T-2 toxin was observed with the NOX inhibitor DPI (<em>P</em> &lt; 0.001), the ERK inhibitor U0126 (P &lt; 0.001), the TLR2 inhibitor C29 (P &lt; 0.001), and the TLR4 inhibitor TLR4-IN-C34 (P &lt; 0.001). T-2 toxin triggered ferroptosis in neutrophils by suppressing GPX4 and FT expression, elevating ROS and lipid ROS, and augmenting the concentration of mitochondrial Fe²⁺. The ferroptosis inhibitor Fer-1 could rescue this induction; however, Fer-1 was unable to inhibit NETs which is induced by T-2 toxin. Conversely, T-2 toxin effectively triggered the downregulation of GPX4, which was counteracted by DPI, U0126, C29, and C34. This research elucidates the immunotoxic mechanisms of T-2 toxin in goat neutrophils and offers a novel perspective on preventing and treating T-2 toxin.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"495 ","pages":"Article 117232"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxic effects of dibutyl phthalate on trophoblast through mitochondria mediated cellular dysfunction","authors":"Hyewon Jang ,&nbsp;Gwonhwa Song ,&nbsp;Whasun Lim ,&nbsp;Sunwoo Park","doi":"10.1016/j.taap.2024.117186","DOIUrl":"10.1016/j.taap.2024.117186","url":null,"abstract":"<div><div>Dibutyl phthalate is a chemical commonly used as a plasticizer in the production of daily necessaries, such as cosmetics and toys. Although several toxic effects of dibutyl phthalate have been confirmed, those related to pregnancy are unknown. Trophoblasts are critical for fetal and placental development, and trophoblast damage may cause preeclampsia. This study aimed to confirm the toxic effect of dibutyl phthalate on trophoblasts. We used the human trophoblast cell line HTR-8/SVneo and human choriocarcinoma JEG-3 cells as a placental trophoblast model to investigate the toxic effects of dibutyl phthalate. Both cell lines were treated with dibutyl phthalate (0–20 μg/mL) to verify the mechanisms regulating trophoblast function. Dibutyl phthalate treatment significantly reduced trophoblast viability, reduced invasion ability, and induced mitochondrial depolarization. Ultimately, dibutyl phthalate regulated the PI3K and MAPK signaling pathways and the expression of autophagy-related proteins ATG5, LC3B, and SQSTM1/p62. We concluded that dibutyl phthalate induced autophagy and effectively weakened trophoblast function. Additionally, we conducted experiments to assess the potential effects of monobutyl phthalate, a metabolite of dibutyl phthalate, on cellular mobility, penetration, and autophagy induction. Our results demonstrated that monobutyl phthalate impaired these functions and weakened the trophoblast barrier, after dibutyl phthalate metabolized. Thus, exposure to dibutyl phthalate and its metabolite monobutyl phthalate can damage trophoblast function, highlighting their potential as hazardous substances that impair trophoblast barrier integrity.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"495 ","pages":"Article 117186"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142795144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolomics based early warning model for acute kidney injury risk in patients exposed to diquat","authors":"Shengkai Zhu ,&nbsp;Xinyu Li ,&nbsp;Chengzhao Wu ,&nbsp;Xu Zhao ,&nbsp;Shuiying Xu ,&nbsp;Yujing Zhao ,&nbsp;Xiaobo Peng ,&nbsp;Xiaohe Xiao ,&nbsp;Ming Niu","doi":"10.1016/j.taap.2024.117207","DOIUrl":"10.1016/j.taap.2024.117207","url":null,"abstract":"<div><div>Acute kidney injury (AKI) is one of the most important indications of severe clinical symptoms in patients with diquat poisoning and is closely related to poor prognosis. However, current studies have rarely focused on early warnings of diquat-related AKI, which is not conducive to the treatment of patients with early clinical diquat poisoning. In this study, untargeted plasma metabolomics was employed to reveal the differences between diquat-poisoned patients with and without AKI, as well as between patients and healthy volunteers. The results showed that 48 metabolites were significantly changed in the patients, among which 3-hydroxybutyrylcarnitine, SAICAR, dodecanoic acid, and tetrahydrofolyl-[Glu](2) could be used to effectively differentiate the above three groups. Based on the ratios of the first two metabolites and the ratios of the last two metabolites, a decision tree model for the early warning of diquat-induced AKI was established with an accuracy rate of 88.7 %. This model provides great support for accurate clinical diagnosis and intervention regarding the AKI risk of diquat-exposed patients.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"495 ","pages":"Article 117207"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety assessment on CBD-rich hemp extract in sub-chronic cross-sex study with rats","authors":"Jan Dehner ,&nbsp;Hana Holcova Polanska ,&nbsp;Katerina Petrlakova ,&nbsp;Sanja Cavar Zeljkovic ,&nbsp;Tibor Beres ,&nbsp;Michal Hendrych ,&nbsp;Jan Storch ,&nbsp;Petr Tarkowski ,&nbsp;Michal Masarik ,&nbsp;Petr Babula ,&nbsp;Jan Vacek","doi":"10.1016/j.taap.2024.117218","DOIUrl":"10.1016/j.taap.2024.117218","url":null,"abstract":"<div><div>Cannabidiol (CBD) is a phytocannabinoid from <em>Cannabis sativa</em> L., in which there is currently growing interest for medicinal use. Here, we focused on the safety and pharmacokinetics of a CBD-rich (77 %, <em>w</em>/<em>w</em>) full-spectrum hemp extract in male and female rats. A 90-day sub-chronic toxicity assay was conducted with doses of 0.5, 5, 10, and 35 mg CBD extract/kg/day administered orogastrically. No adverse effects or disruption in organ or body weight, behaviour, locomotion, food intake, or impact on morbidity/mortality were observed. Pathomorphological examination showed no gastrointestinal or liver changes. Blood cell analysis showed a significant (<em>p</em> &lt; 0.05) decrease in the number of leukocytes for both sexes, and a significant difference (<em>p</em> &lt; 0.01 or 0.05) between the control and treated animals for mean corpuscular haemoglobin concentration, mean corpuscular volume of erythrocytes, and percentage of neutrophils and monocytes. However, blood cell analysis revealed significant (<em>p</em> &lt; 0.05) sex-dependent differences, such as haematocrit and erythrocyte count. The levels of ions (Ca²⁺, Na⁺, K⁺ and Cl⁻), alkaline phosphatase activity, and creatinine level in treated animals were also observed for both sexes. Males exhibited decreased alanine transaminase activities, and females exhibited hyperalbuminemia (<em>p</em> &lt; 0.01). CBD was quantified in treated animals in a dose-dependent manner, with statistical significance varying from <em>p</em> &lt; 0.05 to 0.0001. The accumulation of CBD in the individual tissues increased in the order: brain &lt; serum &lt; liver &lt; heart &lt;&lt; kidney &lt;&lt;&lt; muscle and skin. The results indicated sex-dependent latent disruption of kidney and liver homeostasis, most likely reversible in nature.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"495 ","pages":"Article 117218"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142897828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cadmium biphasically impacts the adaptive immune system via regulating mitochondrial activation of hematopoietic stem cells in mice","authors":"Yifan Zhao ,&nbsp;Chuanxuan Wang ,&nbsp;Jun Du ,&nbsp;Wei Wang ,&nbsp;Jiaojiao Wu ,&nbsp;Ting Liu ,&nbsp;Peng Xue ,&nbsp;Yingzi Ju ,&nbsp;Xinyu Hong ,&nbsp;Jianheng Zheng ,&nbsp;Weidong Qu ,&nbsp;Yubin Zhang","doi":"10.1016/j.taap.2024.117216","DOIUrl":"10.1016/j.taap.2024.117216","url":null,"abstract":"<div><div>Cadmium (Cd) is a highly toxic metal in human body, and therefore understanding the immunotoxicity of Cd is significant for public health. The aim of this study was to investigate the role of hematopoietic stem cells (HSC) in regulating the immunotoxicity of Cd. After exposure to 10 ppm Cd via drinking water for up to 9 months, C57BL/6 mice had a suppressed adaptive immune system at day 135 but had an enhanced adaptive immune system at day 270 during Cd exposure. The biphasic impacts of Cd on the adaptive immune system were correlated to the mitochondrial (MT) activation of HSC. Mechanistically, a direct action of Cd activated the non-canonical Wnt signaling to increase MT activation in HSC in the bone marrow (BM) at day 90, thus resulting in an impaired adaptive immune system in mice at day 135 during Cd exposure; conversely, Cd reduced the production of thrombopoietin (TPO) by osteoblasts in the BM to suppress MT activation in HSC at day 180, which in turn caused an enhanced adaptive immune system in mice at day 270 during Cd exposure. Thus, Cd biphasically impacts the adaptive immune system via regulating MT activation of HSC, providing a novel angle for understanding the immunotoxicology of metals.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"495 ","pages":"Article 117216"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the impact of sub-chronic polyethylene terephthalate nanoplastic exposure on male reproductive health in mice","authors":"Oğuz Kaan Tombul ,&nbsp;Arife Dilşad Akdağ ,&nbsp;Pınar Buket Thomas ,&nbsp;Nur Kaluç","doi":"10.1016/j.taap.2025.117235","DOIUrl":"10.1016/j.taap.2025.117235","url":null,"abstract":"<div><div>The widespread use of polyethylene terephthalate (PET) in food and beverage packaging raises concerns about its potential health effects, particularly when PET-derived nanoplastics (PET-NPs) are released into the environment. This study investigates the reproductive toxicity of PET-NPs in male mice. Mice were exposed to PET-NPs at doses of 0.1 mg/day and 0.5 mg/day for 28 days, and the testes index, sperm count, sperm morphology, Reactive Oxygen Species (ROS) production, DNA integrity, histopathology, and spermatogenesis were evaluated. PET-NP exposure resulted in a significant decrease in sperm concentration and an increase in abnormal spermatozoa—particularly blunt-headed sperm and sperm with neck and tail anomalies— and elevated ROS levels in testicular tissue in a dose-dependent manner (<em>p</em> &lt; 0.05). Additionally, PET-NPs induced DNA strand breaks, as demonstrated by the COMET assay (p &lt; 0.05). Histopathological analysis revealed disorganization of the germinal epithelium, vacuolization, reduced sperm density, and increased interstitial spaces, accompanied by a significant decline in spermatogenic activity, as assessed by Johnsen scoring. These findings strongly suggest that the observed adverse effects on male reproductive health, including sperm abnormalities, DNA damage, and impaired spermatogenesis, are primarily driven by ROS-induced oxidative stress. The observed changes provide clear evidence of the adverse effects of subchronic exposure to PET nanoplastics on male reproductive health, highlighting the inherent risks associated with nanoplastic exposure and offering crucial insights for public health awareness and regulatory considerations.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"495 ","pages":"Article 117235"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing toxicity prediction for natural products in herbal medicine and dietary supplements: Integrating (Q)STR models and in vitro assays","authors":"Hyun Kil Shin ,&nbsp;Se-Myo Park ,&nbsp;Mi-Sun Choi ,&nbsp;Jung-Hwa Oh ,&nbsp;Sang Kyum Kim ,&nbsp;Seokjoo Yoon ,&nbsp;Hae-Ryung Park ,&nbsp;Hyoung-Yun Han","doi":"10.1016/j.taap.2024.117220","DOIUrl":"10.1016/j.taap.2024.117220","url":null,"abstract":"<div><div>New approach methods (NAMs) are required to predict human toxicity effectively, particularly due to limitations in conducting <em>in vivo</em> studies. While NAMs have been established for various industries, such as cosmetics, pesticides, and drugs, their applications in natural products (NPs) are lacking. NPs' complexity (multiple ingredients and structural differences from synthetic compounds) complicates NAM development. In this study, we devised NAMs for NPs using (quantitative) structure-toxicity relationship (Q)STR models and <em>in vitro</em> assays.</div><div>Validation involved testing each method with single compounds isolated from NPs. A linear regression model was developed for (Q)STR prediction (R² on test set: 0.52), with an applicability domain analysis demonstrating its reliability across NPs. This model was applied to predict the LD₅₀ range of species, aiding in the development of herbal medicine and dietary supplements. <em>In vitro</em> screening employed three reporter cell lines (AP-1, P53, and Nrf2), with Tox scores derived by integrating <em>in silico</em> and <em>in vitro</em> data.</div><div>Nimbolide exhibited the highest Tox score, with experimental studies corroborating the accuracy and reliability of the predictions made <em>via</em> Tox score analysis. The findings of the study align well with the purpose, as the suggested NAMs, utilizing (Q)STR models and <em>in vitro</em> assays, provide a Tox score to efficiently prioritize NPs for herbal medicine and dietary supplements.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"495 ","pages":"Article 117220"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ginkgetin enhances breast cancer radiotherapy sensitization by suppressing NRF2-HO-1 axis activity","authors":"Qiong Duan ,&nbsp;Zhenting Cui ,&nbsp;Mingxiao Wang ,&nbsp;Ruochen Li ,&nbsp;Feng Han ,&nbsp;Jianxin Ma","doi":"10.1016/j.taap.2024.117199","DOIUrl":"10.1016/j.taap.2024.117199","url":null,"abstract":"<div><div>Breast cancer (BC) is a critical threat to women's lives. Radiotherapy (RT) is a pivotal treatment modality for BC, but the failure of RT due to radioresistance is still not well facilitated. Ginkgetin (GK) has a potent anti-tumor activity intimately associated with ferroptosis. This study applied in vitro and in vivo experimental models to ascertain the GK mechanism of action on BC radioresistance. The outcomes reported that GK could inhibit BC cell growth and increase apoptosis. In addition, when BC cells generated radioresistance, GK promoted ferroptosis of radioresistant BC cells by mitigating NRF2 expression, suppressing HO-1 and NQO1 expression, increasing the intracellular content of reactive oxygen species (ROS) and ferrous ions, accelerating the glutathione (GSH) depletion, and decreasing GPX4 expression. Notably, GK can damage intracellular mitochondria and cause a substantial increase in ferrous ions in BC cells. Therefore, GK shows immense potential for enhancing breast cancer radiotherapy sensitivity, which may provide pivotal evidence for subsequent RT sensitization.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"495 ","pages":"Article 117199"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}