Toxicology and applied pharmacology最新文献_第4页

Neurotoxicity study of cenobamate-induced zebrafish early developmental stages.

IF 3.3 3区医学

Toxicology and applied pharmacology Pub Date : 2024-12-10 DOI: 10.1016/j.taap.2024.117201

Jiahao Liu, Liya Fang, Chao Gong, Jiawei Li, Yuanyuan Liu, Pei Zeng, Yanping Fan, Yao Liu, Jin Guo, Luchuan Wang, Yue Li

{"title":"Neurotoxicity study of cenobamate-induced zebrafish early developmental stages.","authors":"Jiahao Liu, Liya Fang, Chao Gong, Jiawei Li, Yuanyuan Liu, Pei Zeng, Yanping Fan, Yao Liu, Jin Guo, Luchuan Wang, Yue Li","doi":"10.1016/j.taap.2024.117201","DOIUrl":"10.1016/j.taap.2024.117201","url":null,"abstract":"Cenobamate (CNB) is a novel anti-seizure medication with significant efficacy in treating epilepsy. However, in clinical trials, the most common adverse reactions observed in patients are central nervous system (CNS) symptoms. In animal studies, administration of CNB during pregnancy or lactation has been associated with adverse effects on neurodevelopment in offspring. To optimize the clinical use of CNB, we investigated the neurotoxicity of different concentrations of CNB (10, 20, 40, 80, and 160 μM) on zebrafish embryos. Following exposure, zebrafish embryos exhibited abnormal phenotypes such as shortened body length, impaired yolk sac absorption, and decreased heart rate. Behavioral experiments showed that CNB caused abnormal movements such as decreased spontaneous tail curling frequency, shortened total movement distance, and reduced average movement speed. We also found that CNB leads to increased acetylcholinesterase (AChE) activity levels in zebrafish embryos, along with differential expression of neurodevelopment-related genes such as nestin, gfap, synapsin IIa, and gap43. In summary, our research findings indicated that CNB may induce developmental and neurotoxic effects in zebrafish embryos by altering neurotransmitter systems and the expression of neurodevelopmental genes, thereby influencing behavior. This study will provide information for the clinical use of CNB, aiming to benefit more epilepsy patients through its appropriate administration.","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":" ","pages":"117201"},"PeriodicalIF":3.3,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819329","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}

引用次数: 0

Epigallocatechin gallate ameliorates retinal pigment epithelial cell damage via the CYFIP2 /AKT pathway.

IF 3.3 3区医学

Toxicology and applied pharmacology Pub Date : 2024-12-10 DOI: 10.1016/j.taap.2024.117124

Sijia Li, Dongmei Su, Shanshan Hu, Qiang Hu, Dawei Sun

{"title":"Epigallocatechin gallate ameliorates retinal pigment epithelial cell damage via the CYFIP2 /AKT pathway.","authors":"Sijia Li, Dongmei Su, Shanshan Hu, Qiang Hu, Dawei Sun","doi":"10.1016/j.taap.2024.117124","DOIUrl":"10.1016/j.taap.2024.117124","url":null,"abstract":"Age-related macular degeneration (AMD) is a representative age-related ophthalmic disease, and the pathogenesis of AMD remains unclear. This research intended to determine whether epigallocatechin gallate (EGCG) could alleviate the progression of AMD and the possible mechanism. We constructed three groups of mice (young, aged, and EGCG), and HE and TUNEL staining of retinal tissues was performed to observe the structural changes in the retinal pigment epithelial (RPE) layer and the level of apoptosis, respectively. Through RNA-Sequencing analysis of retinal tissues and by RT-qPCR, GO, KEGG, and literature analyses, we identified cytoplasmic fragile X mental retardation 1-interacting protein 2 (CYFIP2) as a possible effector gene for EGCG action and validated its role by immunofluorescent and western blotting experiments. The CCK-8 and Hoechst 33342 apoptosis assays, and western blotting and qRT-PCR assays showed that EGCG reduced hydrogen peroxide (H2O2)-induced apoptosis in adult human RPE (ARPE-19) cells, and the expression of Cyfip2 was changed accordingly. RNA interference analysis indicated that Cyfip2 knockdown alleviated H2O2-induced ARPE apoptosis, while its overexpression weakened EGCG's protective effect. Western blot analysis showed that Cyfip2 mediated the anti-apoptotic effect of EGCG by modulating the level of protein kinase B (Akt) phosphorylation in ARPE cells, and the activation level of phosphorylated AKT (p-AKT Ser473) in retinal tissue of the EGCG-fed group was higher than that of the aged group. Taken together, this study suggests that EGCG plays a protective role in the development of AMD and the apoptosis of ARPE cells through the Cyfip2/AKT pathway.","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":" ","pages":"117124"},"PeriodicalIF":3.3,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819295","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}

引用次数: 0

Exposure to environmentally relevant concentrations of di-(2-ethylhexyl) phthalate (DEHP) induced reproductive toxicity in female koi carp (Cyprinus carpio).

IF 3.3 3区医学

Toxicology and applied pharmacology Pub Date : 2024-12-09 DOI: 10.1016/j.taap.2024.117200

Kampan Bisai, Vikash Kumar, Basanta Kumar Das, Bijay Kumar Behera, Manoj Kumar Pati

{"title":"Exposure to environmentally relevant concentrations of di-(2-ethylhexyl) phthalate (DEHP) induced reproductive toxicity in female koi carp (Cyprinus carpio).","authors":"Kampan Bisai, Vikash Kumar, Basanta Kumar Das, Bijay Kumar Behera, Manoj Kumar Pati","doi":"10.1016/j.taap.2024.117200","DOIUrl":"10.1016/j.taap.2024.117200","url":null,"abstract":"A frequently utilized plasticizer is di-(2-ethylhexyl) phthalate (DEHP), considered a ubiquitous contaminant in the environment and reported to have severe impacts on animals. Although it disrupts the female reproductive system in mammals, little is known about how it effects on fish reproduction. The reproductive parameters of female adult koi carp (Cyprinus carpio) were investigated in this study subjected to environmentally relevant exposure of DEHP (1, 10 and 100 μg/L). After 60 days experiment, significantly lower GSI was recorded in females of 10 and 100 μg/L DEHP-exposed groups. The examination of ovarian histology showed defective histoarchitecture, which included the existence of atretic oocytes, the emergence of intra-oocyte vacuoles as well as necrosis. The groups exposed to DEHP (10 and 100 μg/L) showed significant decreases in fecundity and ova-diameter values. Significant changes in the biochemical (total protein, glucose and cholesterol) and ionic (sodium, potassium, calcium and magnesium) composition were noticed in the ovarian fluid of exposed groups. The groups treated with DEHP showed higher levels of 11-ketotestosterone along with reduced levels of 17β-estradiol. Using real-time PCR, the mRNA expression of several genes linked to reproduction, such as Fshr, Lhr, Ar, Erα and Erβ were assessed and observed that there was a concentration-dependent alternation. The pairing of exposed females with untreated males significantly lowered the rates of fertilization, hatching and larval survival. In summary, the results of this investigation validated that exposure to DEHP in a nominal concentration could potentially reduce the reproductive health of female fish.","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":" ","pages":"117200"},"PeriodicalIF":3.3,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814236","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}

引用次数: 0

Ginkgetin enhances breast cancer radiotherapy sensitization by suppressing NRF2-HO-1 axis activity. 银杏黄酮通过抑制 NRF2-HO-1 轴活性增强乳腺癌放疗的敏感性

IF 3.3 3区医学

Toxicology and applied pharmacology Pub Date : 2024-12-07 DOI: 10.1016/j.taap.2024.117199

Qiong Duan, Zhenting Cui, Mingxiao Wang, Ruochen Li, Feng Han, Jianxin Ma

{"title":"Ginkgetin enhances breast cancer radiotherapy sensitization by suppressing NRF2-HO-1 axis activity.","authors":"Qiong Duan, Zhenting Cui, Mingxiao Wang, Ruochen Li, Feng Han, Jianxin Ma","doi":"10.1016/j.taap.2024.117199","DOIUrl":"10.1016/j.taap.2024.117199","url":null,"abstract":"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.","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":" ","pages":"117199"},"PeriodicalIF":3.3,"publicationDate":"2024-12-07","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}

引用次数: 0

Toxic effects of dibutyl phthalate on trophoblast through mitochondria mediated cellular dysfunction.

IF 3.3 3区医学

Toxicology and applied pharmacology Pub Date : 2024-12-06 DOI: 10.1016/j.taap.2024.117186

Hyewon Jang, Gwonhwa Song, Whasun Lim, Sunwoo Park

{"title":"Toxic effects of dibutyl phthalate on trophoblast through mitochondria mediated cellular dysfunction.","authors":"Hyewon Jang, Gwonhwa Song, Whasun Lim, Sunwoo Park","doi":"10.1016/j.taap.2024.117186","DOIUrl":"10.1016/j.taap.2024.117186","url":null,"abstract":"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.","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":" ","pages":"117186"},"PeriodicalIF":3.3,"publicationDate":"2024-12-06","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}

引用次数: 0

Analysis of children's kidney stones and comparison to canine kidney stones: Both resulting from ingesting adulterated food products.

IF 3.3 3区医学

Toxicology and applied pharmacology Pub Date : 2024-12-06 DOI: 10.1016/j.taap.2024.117190

James A Campbell, Catherine E Petersen

{"title":"Analysis of children's kidney stones and comparison to canine kidney stones: Both resulting from ingesting adulterated food products.","authors":"James A Campbell, Catherine E Petersen","doi":"10.1016/j.taap.2024.117190","DOIUrl":"10.1016/j.taap.2024.117190","url":null,"abstract":"Kidney stones resulting from ingestion of melamine-tainted food products were originally detected in dogs and cats in 2004 and 2007. Nephroliths were removed at necropsy from dogs that had died from acute kidney injury in Asia in 2004. Samples of these were submitted to our laboratories for analysis. The presence of a mixed s-triazine matrix comprising melamine, cyanuric acid, and ammelide, but no detectable ammeline was found in the canine stone samples we analyzed. The unusual and unique green coloration of these stones was attributed to the presence of biliverdin. The techniques developed in the canine study were applied to the analysis of human kidney stones. In 2008, high levels of melamine were detected in some infant formula and other liquid and powdered milk products originating from China. Human kidney stones, resulting from this type of contamination, were obtained from children, and analyzed using mass spectral techniques. The results indicated the presence of melamine, ammeline, uric acid, but no ammelide. No green color was observed, thereby eliminating biliverdin. Careful monitoring of food additives is warranted to prevent future problems in both animals and humans.","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":" ","pages":"117190"},"PeriodicalIF":3.3,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142795135","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}

引用次数: 0

Preclinical safety and efficacy of the recombinant CR1 drug product CSL040 in rats and cynomolgus monkeys.

IF 3.3 3区医学

Toxicology and applied pharmacology Pub Date : 2024-12-06 DOI: 10.1016/j.taap.2024.117191

Tanja Ruthsatz, Sandra Wymann, Elena Velkoska, Mariam Mansour, Daniel Schu, Marit Lichtfuss, Paolo Rossato, Meaghan FitzPatrick, Sarah Hosback, Allison Dyson, Eva Herzog, Kirstee Martin, Barbara Dietrich, Matthew P Hardy

{"title":"Preclinical safety and efficacy of the recombinant CR1 drug product CSL040 in rats and cynomolgus monkeys.","authors":"Tanja Ruthsatz, Sandra Wymann, Elena Velkoska, Mariam Mansour, Daniel Schu, Marit Lichtfuss, Paolo Rossato, Meaghan FitzPatrick, Sarah Hosback, Allison Dyson, Eva Herzog, Kirstee Martin, Barbara Dietrich, Matthew P Hardy","doi":"10.1016/j.taap.2024.117191","DOIUrl":"10.1016/j.taap.2024.117191","url":null,"abstract":"CSL040 is a soluble, recombinant fragment of the complement receptor 1 (CR1) extracellular domain that acts as an inhibitor of all three pathways of the complement system. Systemic toxicity, toxicokinetics (TK), and pharmacodynamics (PD) of CSL040 were assessed in two-week intravenous (IV) bolus studies in Han Wistar rats and cynomolgus monkeys. Recovery from any effects was evaluated during a four-week recovery period. Daily repeat-dose administration for 2 weeks at doses of up to 500 mg/kg CSL040 IV was well tolerated in rats and cynomolgus monkeys, leading to a no observed adverse effect level (NOAEL) of 500 mg/kg for both species. Safety pharmacology parameters such as electrophysiology of the heart, blood pressure, heart rate, and respiratory rate measurements, and general toxicological readouts were considered unaffected by CSL040 treatment. Anti-drug antibodies (ADAs) were observed in all cynomolgus monkeys and in some rats at the highest dose of CSL040, but with no effect on pharmacokinetics (PK), supportive of adequate exposure levels as required for a safety assessment. All three complement pathways were inhibited dose-dependently by CSL040. Additionally, no effect on cytokine levels by CSL040 was detected in vitro using a cytokine release assay. These non-clinical studies with CSL040 demonstrated PD activity consistent with its mode of action, adequate PK properties, and a safety profile supporting a phase 1 clinical strategy. A small follow-up study comparing the PK/PD effects of CSL040 following IV and subcutaneous (SC) administration also suggested that the latter route of administration might be a viable alternative to IV administration.","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":" ","pages":"117191"},"PeriodicalIF":3.3,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142795138","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}

引用次数: 0

An oat fiber intervention for reducing PFAS body burden: A pilot study in male C57Bl/6 J mice.

IF 3.3 3区医学

Toxicology and applied pharmacology Pub Date : 2024-12-06 DOI: 10.1016/j.taap.2024.117188

Jennifer J Schlezinger, Kushal Biswas, Audrey Garcia, Wendy J Heiger-Bernays, Dhimiter Bello

{"title":"An oat fiber intervention for reducing PFAS body burden: A pilot study in male C57Bl/6 J mice.","authors":"Jennifer J Schlezinger, Kushal Biswas, Audrey Garcia, Wendy J Heiger-Bernays, Dhimiter Bello","doi":"10.1016/j.taap.2024.117188","DOIUrl":"10.1016/j.taap.2024.117188","url":null,"abstract":"Perfluoroalkyl substances (PFAS) are a major public health concern, in part because several PFAS have elimination half-lives on the order of years and are associated with adverse health outcomes. While PFAS can be transported into bile, their efficient reuptake by intestinal transporter proteins results in minimal fecal elimination. Here, we tested the hypothesis that consumption of oat β-glucan, a dietary supplement known to disrupt the enterohepatic recirculation of bile acids, will reduce PFAS body burdens. Male C57Bl/6 J mice were fed diets based on the \"What we eat in America\" analysis that were supplemented with inulin or oat β-glucan and exposed via drinking water to a seven PFAS mixture (PFHpA, PFOA, PFNA, Nafion Byproduct-2, PFHxS and PFOS) for 6 weeks. One cohort of mice was euthanized at the end of the exposure, and one cohort continued on the experimental diets for 4 more weeks without additional PFAS exposure. The β-glucan fed mice drank significantly more water than the inulin fed mice, resulting in a significantly higher dose of PFAS. Relative to overall exposure, we observed lower serum concentration trends (p < 0.1) in β-glucan fed mice for PFHpA, PFOA and PFOS. Additionally, β-glucan fed mice had lower adipose:body weight ratios and liver and jejunum triglyceride concentrations. Hepatic mRNA expression of Cyp4a10, Cyp2b10 and Cyp3a11 were elevated in PFAS exposed mice, with only the expression of Cyp3a11 decreasing following depuration. This pilot study generates support for the hypothesis that oat β-glucan supplementation can reduce PFAS body burdens and stimulate healthful effects on lipid homeostasis.","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":" ","pages":"117188"},"PeriodicalIF":3.3,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142795133","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}

引用次数: 0

Protective effect of thymoquinone against doxorubicin-induced cardiotoxicity and the underlying mechanism.

IF 3.3 3区医学

Toxicology and applied pharmacology Pub Date : 2024-12-05 DOI: 10.1016/j.taap.2024.117179

Yi Chen, Wei Luo, Yanqing Wu

{"title":"Protective effect of thymoquinone against doxorubicin-induced cardiotoxicity and the underlying mechanism.","authors":"Yi Chen, Wei Luo, Yanqing Wu","doi":"10.1016/j.taap.2024.117179","DOIUrl":"https://doi.org/10.1016/j.taap.2024.117179","url":null,"abstract":"Background: Ferroptosis is a key process in doxorubicin (DOX)-induced cardiotoxicity and is a potentially important therapeutic target. Thymoquinone (TQ) is a monoterpenoid compound isolated from black cumin extract that exhibits antitumor effects and acts as a powerful mitochondrial-targeted antioxidant. In this study, we investigated the effect of TQ on DOX-induced cardiotoxicity and the potential underlying mechanisms.Methods and results: Mice were randomly assigned to the control (CON) group, DOX (20 mg/kg) group, TQ10 (10 mg/kg/d) group, and TQ20 (20 mg/kg/d) group and intraperitoneally injected with DOX and different doses of TQ. The electrocardiogram, blood pressure, and cardiac ultrasound changes during the experiments showed that TQ exerted a protective effect against DOX-induced cardiotoxicity. The glutathione (GSH), malondialdehyde (MDA), and total antioxidant capacity (T-AOC) levels in the mouse heart tissue were significantly different from those in the CON group. Western blot analysis revealed that the expression of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), glutathione peroxidase 4 (GPX4), and ferritin heavy chain 1 (FTH1) in the DOX group was lower than that in the control group. TQ treatment decreased these changes, indicating that TQ alleviated DOX-induced cardiotoxicity and increased the antioxidant capacity of murine cardiomyocytes. The mechanism might involve activating the Nrf2/HO-1 signaling pathway and reducing iron-mediated death. Immunohistochemical staining revealed similar effects on the expression levels of NQO1, COX-2, and NOX4. Moreover, transmission electron microscopy indicated that TQ protected murine cardiomyocytes against DOX-induced mitochondrial damage.Conclusion: The results of this study suggested that TQ can decrease oxidative stress levels and DOX-induced cardiotoxicity by activating the Nrf2/HO-1 signaling pathway to alleviate ferroptosis in murine cardiomyocytes.","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":" ","pages":"117179"},"PeriodicalIF":3.3,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792339","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}

引用次数: 0

Corrigendum to "Differentiation of sow and mouse ovarian granulosa cells exposed to zearalenone in vitro using RNA-seq gene expression" [Toxicology and Applied Pharmacology, 350 (2018) 78-90].

IF 3.3 3区医学

Toxicology and applied pharmacology Pub Date : 2024-12-04 DOI: 10.1016/j.taap.2024.117189

Guo-Liang Zhang, Jun-Lin Song, Yi Zhou, Rui-Qian Zhang, Shun-Feng Cheng, Xiao-Feng Sun, Guo-Qing Qin, Wei Shen, Lan Li

引用次数: 0