Human & experimental toxicology最新文献

Human & experimental toxicology Pub Date : 2025-01-01 DOI: 10.1177/09603271241310364

引用次数: 0

Enhancing breast cancer treatment: Evaluating the efficacy of hyaluronic acid-coated tamoxifen-loaded solid lipid nanoparticles on MCF7 cells.

Human & experimental toxicology Pub Date : 2025-01-01 DOI: 10.1177/09603271251322531

Niloufar Ghayoumipour, Hossein Ghafouri

{"title":"Enhancing breast cancer treatment: Evaluating the efficacy of hyaluronic acid-coated tamoxifen-loaded solid lipid nanoparticles on MCF7 cells.","authors":"Niloufar Ghayoumipour, Hossein Ghafouri","doi":"10.1177/09603271251322531","DOIUrl":"https://doi.org/10.1177/09603271251322531","url":null,"abstract":"Introduction: Tamoxifen (TMX) shows promise in treating breast cancer, but it faces challenges such as poor solubility, instability, and incomplete release when targeting tumors. Additionally, TMX therapy's toxicity is a critical issue in breast cancer treatment. This study aimed to assess the impact of hyaluronic acid (HA)-coated TMX-loaded solid lipid nanoparticles (HA-TMX-SLNs) on MCF7 breast cancer cells.Methods: Solid lipid nanoparticles (SLNs) were prepared using hot homogenization. The HA-TMX-SLNs and TMX-SLNs were characterized and evaluated through transmission electron microscopy (TEM). Cytotoxicity was assessed using the MTT assay, and Western blot analysis was utilized to identify key factors in the cell cycle and apoptosis.Results: The nanoparticles (HA-TMX-SLNs) demonstrated approximately 55% loading efficiency after 100 h. HA-TMX-SLNs exhibited lower cytotoxicity in MCF7 cells compared to other treatments. Significant decreases in expression levels of cyclin-dependent kinase (CDK) 4, Cyclin D1, CDK2, and Bcl2 were observed after treatment with HA-TMX-SLNs, along with an increase in cleaved/procaspase-7.Discussion: The in vitro release study showed that HA-coated SLNs consistently released the drug into the media under controlled conditions. Furthermore, HA-TMX-SLNs exhibited cytotoxic effects, increasing apoptosis and inhibiting cancer cell proliferation. These findings suggest that HA-TMX-SLNs effectively deliver TMX to breast cancer cells.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251322531"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143461174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Activation of SIRT3/AMPK/mTOR-mediated autophagy promotes quercetin-induced ferroptosis in oral squamous cell carcinoma.

Human & experimental toxicology Pub Date : 2025-01-01 DOI: 10.1177/09603271251323753

Jin Wang, Jia-Hui Yang, Di Xiong, Ling Chen

{"title":"Activation of SIRT3/AMPK/mTOR-mediated autophagy promotes quercetin-induced ferroptosis in oral squamous cell carcinoma.","authors":"Jin Wang, Jia-Hui Yang, Di Xiong, Ling Chen","doi":"10.1177/09603271251323753","DOIUrl":"https://doi.org/10.1177/09603271251323753","url":null,"abstract":"Introduction: Quercetin has been reported to inhibit the growth of oral squamous cell carcinoma (OSCC), but the mechanism remains unclear. Therefore, our study aimed to investigate the involvement of sirtuin 3 (SIRT3) and the autophagy-dependent form of cell death, ferroptosis, in the pathogenesis of OSCC, and observe the impacts of quercetin on ferroptosis and SIRT3/AMPK/mTOR-mediated autophagy.Methods: SIRT3 knock out or overexpressing SCC15 cell line was generated, treated with indicated drugs, and malondialdehyde (MDA) and ROS levels were measured. Roles of SIRT3 in regulating autophagy-mediated ferroptosis were assessed by immunoprecipitation and Western blotting.Results: SIRT3 overexpression increased levels of MDA and ROS, reducing cell viability, and SIRT3 knockout produced the opposing effect. SIRT3 overexpression upregulated ATG16L1 expression and the conversion of LC3-Ⅰ to LC3-Ⅱ, triggering autophagy. Suppression of autophagy by ATG16L1 knockout impaired SIRT3-triggered ferroptosis. Use of an AMPK inhibitor antagonized the induction of ferroptosis by SIRT3 in SCC15 cells, indicating the involvement of the AMPK/mTOR pathway. Additionally, quercetin significantly increased the levels of SIRT3, p-AMPK, ATG16L1, and the ratio of LC3-Ⅱ/Ⅰ, but reduced cell viability and p-mTOR in SCC15 cells. Autophagy and AMPK inhibitors, or SIRT3 deletion significantly antagonized the impacts of quercetin on the autophagy-mediated ferroptosis in cancer cells.Discussion: SIRT3 overexpression activated the AMPK/mTOR pathway and triggered ATG16L1-mediated autophagy, promoting ferroptosis in SCC15 cells, and we proposed that quercetin may be a promising therapeutic drug for OSCC.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251323753"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Insights into therapeutic potential and practical applications of natural toxins from poisonous mushrooms.

Human & experimental toxicology Pub Date : 2025-01-01 Epub Date: 2025-03-11 DOI: 10.1177/09603271251323134

Tharuka Wijesekara, Baojun Xu

{"title":"Insights into therapeutic potential and practical applications of natural toxins from poisonous mushrooms.","authors":"Tharuka Wijesekara, Baojun Xu","doi":"10.1177/09603271251323134","DOIUrl":"https://doi.org/10.1177/09603271251323134","url":null,"abstract":"IntroductionMushrooms, belonging to the phyla Ascomycota and Basidiomycota, comprise approximately 14,000 known species, among which a small fraction are toxic. While toxic mushrooms are primarily associated with adverse health effects, recent research highlights their potential as sources of bioactive compounds with promising therapeutic applications.MethodsA systematic review was conducted using four major electronic databases: Web of Science, Google Scholar, PubMed, and ScienceDirect. The literature search, completed on July 1, 2024, utilized keywords including \"Poisonous mushrooms,\" \"Mushroom toxins,\" \"Mycotoxins,\" \"Beta-glucans,\" \"Psilocybin,\" and \"Therapeutic applications.\" Articles were selected based on specific inclusion criteria, focusing on studies investigating the biochemical, toxicological, and pharmacological properties of toxic mushroom compounds. Studies unrelated to mushrooms, non-peer-reviewed sources, or those with outdated or incomplete data were excluded.ResultsThis review examines key toxic mushroom compounds such as amanitins, phallotoxins, ibotenic acid, muscimol, orellanine, and gyromitrin, emphasizing their biosynthesis, structural features, and health effects. Despite their toxicity, compounds like beta-glucans, polysaccharides, lectins, and psilocybin exhibit immune-modulating, anticancer, and neuroprotective properties. These bioactive compounds have shown promise in targeting cancer stem cells and enhancing neurotransmitter activity, positioning them as potential therapeutic agents.DiscussionUnderstanding the therapeutic potential of toxic mushroom-derived bioactive compounds bridges toxicology and pharmacology, offering novel avenues for drug discovery. Comparative analysis with existing treatments highlights their unique advantages in modern medicine.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251323134"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143607619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Conflicts of interest in the International Agency for Research on Cancer process of identifying carcinogenic hazards to humans.

Human & experimental toxicology Pub Date : 2025-01-01 DOI: 10.1177/09603271241269020

Susan A Elmore, Colin Berry, Brad Bolon, Gary A Boorman, Alys E Bradley, Samuel M Cohen, James E Klaunig, Felix M Kluxen, Robert R Maronpot, Abraham Nyska, Tracey L Papenfuss, Jerold E Rehg, David B Resnik, Ivonne McM Rietjens, Thomas J Rosol, Andrew W Suttie, Trenton R Schoeb, Christian Strupp, Bob Thoolen, Klaus Weber

{"title":"Conflicts of interest in the International Agency for Research on Cancer process of identifying carcinogenic hazards to humans.","authors":"Susan A Elmore, Colin Berry, Brad Bolon, Gary A Boorman, Alys E Bradley, Samuel M Cohen, James E Klaunig, Felix M Kluxen, Robert R Maronpot, Abraham Nyska, Tracey L Papenfuss, Jerold E Rehg, David B Resnik, Ivonne McM Rietjens, Thomas J Rosol, Andrew W Suttie, Trenton R Schoeb, Christian Strupp, Bob Thoolen, Klaus Weber","doi":"10.1177/09603271241269020","DOIUrl":"https://doi.org/10.1177/09603271241269020","url":null,"abstract":"Managing conflicts of interest (COIs) in scientific decision-making is important for minimizing bias and fostering public trust in science. Proper management of COIs has added significance when scientists are making decisions that impact public policy, such as assessing substances for carcinogenicity. The International Agency for Research on Cancer (IARC) organizes expert working groups to identify putative carcinogens and determine whether or not the hazard is likely to present significant potential harm to humans. While IARC has policies for managing COIs, prior professional experience with the substance being assessed is not defined as a COI. Indeed, IARC working group members are chosen based on subject matter expertise, including prior publication on the substance under review. However, a person's prior experience with a substance poses a significant potential COI by equipping them with strong pre-existing views about the substance's toxicity and carcinogenicity. To minimize the risk of bias in IARC working groups, participants with voting powers should be independent scientific experts with sufficient professional experience to review carcinogenicity data but with no substantial prior experience with the substance under review. A related IARC practice restricting data review by working groups to selected publications is another significant COI. Instead, all accessible data should be available for consideration by working groups in assessing the carcinogenic hazard of substances. Another recommendation to reduce potential bias would be to reinstate the option of \"probably not carcinogenic to humans\".","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271241269020"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Down-regulation of E2F1 attenuates UVB-induced human lens epithelial cell oxidative stress and pyroptosis through inhibiting NLRP3. 下调E2F1通过抑制NLRP3减弱uvb诱导的人晶状体上皮细胞氧化应激和焦亡。

Human & experimental toxicology Pub Date : 2025-01-01 DOI: 10.1177/09603271241309258

Fang Wang, Fan Yang, Guiqi Yang, Qi Zhou, Hongbin Lv

{"title":"Down-regulation of E2F1 attenuates UVB-induced human lens epithelial cell oxidative stress and pyroptosis through inhibiting NLRP3.","authors":"Fang Wang, Fan Yang, Guiqi Yang, Qi Zhou, Hongbin Lv","doi":"10.1177/09603271241309258","DOIUrl":"https://doi.org/10.1177/09603271241309258","url":null,"abstract":"Background: It is well-known that ultraviolet B (UVB) causes cataracts by inducing pyroptosis and the production of reactive oxygen species (ROS) in human lens epithelial cells (HLECs). The transcription factor E2F1 (E2F1) serves as a positive regulator of disrupted pathways involved in histone modification and cell cycle regulation. However, its function in UVB-treated HLECs remains unknown.Purpose: This study aims to investigate the function of E2F1 in UVB-treated HLECs, with a particular focus on its interaction with NLRP3 and its impact on oxidative stress and pyroptosis. Research Design: HLECs were irradiated with UVB, and cell damage was assessed using CCK-8, ROS, and pyroptosis detection. The interaction between E2F1 and NLRP3 was confirmed using Chromatin immunoprecipitation (ChIP)-qPCR and dual-luciferase reporter assays.Study Sample: The study was conducted using UVB-treated HLECs.Data collection and/or analysis: Collected data were statistically analyzed using one-way analysis of variance (ANOVA).Results: Our results show that HLECs were much more susceptible to oxidative stress, pyroptosis, and E2F1 in response to UVB-irradiation, but that E2F1 down-regulation effectively counteracted these effects. E2F1 was then suggested as a potential NLRP3 transcription factor by bioinformatics studies. At the same time, luciferase and CHIP assays showed that E2F1 could bind to the NLRP3 promoter and enhance NLRP3 transcription. In addition, the protective effects of si-E2F1 against oxidative stress and pyroptosis in HLECs are counteracted by overexpressing NLRP3.Conclusions: All of the above provided the possibility to demonstrate that E2F1 plays a crucial role in regulating oxidative stress and pyroptosis in UVB-induced HLECs through inhibiting NLRP3, and it promotes oxidative stress-induced pyroptosis by suppressing NLRP3 expression.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271241309258"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142934227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The acute and sub-chronic toxicological effects of 3-amino-9-ethylcarbazole (AEC) on zebrafish. 3-amino-9-ethylcarbazole (AEC) 对斑马鱼的急性和亚慢性毒理效应。

Human & experimental toxicology Pub Date : 2025-01-01 DOI: 10.1177/09603271251318968

Erna Vásárhelyi, Gergely Rácz, Béla Urbányi, Balázs P Szabó, Dóra Szepesi-Bencsik, István Szabó, Illés Bock, Cintia Volner, Jeffrey Daniel Griffitts, Balázs Kriszt, Katalin Bakos, Zsolt Csenki

{"title":"The acute and sub-chronic toxicological effects of 3-amino-9-ethylcarbazole (AEC) on zebrafish.","authors":"Erna Vásárhelyi, Gergely Rácz, Béla Urbányi, Balázs P Szabó, Dóra Szepesi-Bencsik, István Szabó, Illés Bock, Cintia Volner, Jeffrey Daniel Griffitts, Balázs Kriszt, Katalin Bakos, Zsolt Csenki","doi":"10.1177/09603271251318968","DOIUrl":"https://doi.org/10.1177/09603271251318968","url":null,"abstract":"Introduction: In this study, we sought to determine the sub-chronic toxicological effects of AEC on zebrafish embryos.Methods: We utilized fish early life stage (FELS) and fish embryo toxicity (FET) tests, vascular, neurological, and renal transgenic zebrafish lines, and gene expression anal-ysis of the zebrafish tissue.Results: In the FET tests, AEC caused several abnormalities in the larvae, with the LC50 at 24 hpf being 4.076 ± 0.221 mg/L and 3.296 ± 0.127 mg/L at 96 hpf. In the FELS test, AEC was shown to be lethal following 16 days of exposure at 0.5 mg/L, 1 mg/L and 2 mg/L. Some of the transgenic zebrafish lines exhibited slight changes in fluorescent signaling pat-terns after exposure to AEC at 1 mg/L and 2 mg/L. Notable results of the gene expression analysis revealed: gpx4b and got2 were downregulated in the liver; HIF1a was downregulated at 0.25 mg/L and 0.5 mg/L concentrations, NOTCH1a and fli-1 genes were downregulated at all concentrations, and A2b was upregulated in the vasculature; a1T, ngn1, elavl3, syn2a, mbp, gap43 were down-regulated in the nervous system; and wt1b was downregulated in the kidney.Discuccion: Altogether, the results of our study indicate the potential for AEC to cause harm to organisms.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251318968"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143470429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Rhynchophylline promotes microglia phenotypic transformation and repair of cerebral ischaemic injury through the JAK2/STAT3 pathway. 黄连素通过 JAK2/STAT3 通路促进小胶质细胞表型转化和脑缺血损伤的修复。

Human & experimental toxicology Pub Date : 2025-01-01 DOI: 10.1177/09603271251324582

Peng Bai, Caixia Li, Luwei Yin, Yao Li, Meng Ju, Laicang Wang

{"title":"Rhynchophylline promotes microglia phenotypic transformation and repair of cerebral ischaemic injury through the JAK2/STAT3 pathway.","authors":"Peng Bai, Caixia Li, Luwei Yin, Yao Li, Meng Ju, Laicang Wang","doi":"10.1177/09603271251324582","DOIUrl":"https://doi.org/10.1177/09603271251324582","url":null,"abstract":"Background: Rhynchophylline (RIN) is an alkaloid known for its ability to effectively block signal transduction related to various neurodegenerative diseases. However, the specific mechanism by which RIN regulates microglial activation and cerebral ischemia remains unexplored. This study aims to investigate the function and molecular pathways through which RIN activates the JAK2/STAT3 signaling cascade, promoting the transformation of microglial phenotypes that contribute to recovery from cerebral ischemic injury.Methods: By establishing a microglia oxygen glucose deprivation/reoxygenation (OGD/R) model and a middle cerebral artery occlusion animal model, we assessed changes in the expression of phenotype-specific marker factors for M1 and M2 microglia, as well as key proteins in the JAK2/STAT3 pathway, utilizing ELISA and Western blot techniques. Histological examination, including HE staining, TUNEL assay, and immunofluorescence, was employed to evaluate pathological changes in brain tissue, along with cell apoptosis and proliferation.Results: The results indicated that microglial activity was significantly reduced and shifted towards the M1 phenotype following OGD/R. However, RIN treatment reversed these changes. When JAK2/STAT3 inhibitors were combined with RIN, it inhibited RIN's protective effect. Animal studies have shown that RIN reduces histopathological changes associated with cerebral ischemia. Additionally, RIN inhibited microglial proliferation in ischemic cortical tissue and increased the expression of M2-type marker proteins, as well as the levels of phosphorylated JAK2 and STAT3 in the ischemic tissue.Conclusion: In conclusion, this study indicates that RIN may protect against cerebral ischemic injury by activating the JAK2/STAT3 pathway, which promotes the transition of microglia to the M2 phenotypic.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251324582"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

KLF9 mediates NLRP3 inflammasome and reactive oxygen species to mediate pyroptosis in trophoblasts.

Human & experimental toxicology Pub Date : 2025-01-01 Epub Date: 2025-03-11 DOI: 10.1177/09603271251324702

Qian Li, Min Chen

{"title":"KLF9 mediates NLRP3 inflammasome and reactive oxygen species to mediate pyroptosis in trophoblasts.","authors":"Qian Li, Min Chen","doi":"10.1177/09603271251324702","DOIUrl":"https://doi.org/10.1177/09603271251324702","url":null,"abstract":"IntroductionThe objective of this study was to explore the effect of KLF9 on oxidative stress (OS) and NLRP3-mediated inflammation in preeclampsia (PE).MethodsLipopolysaccharide (LPS)+adenosine triphosphate (ATP)-induced HTR-8/SVneo cells were used as an in vitro PE inflammation cell model. shRNA was used to interfere with KLF9 expression (sh-KLF9) to assess the transfection efficiency and the effect of KLF9 on cell proliferation, migration, and invasion. ELISA was performed to detect OS-related factors and inflammatory cytokines. Reactive oxygen species (ROS) levels and pyroptosis were analyzed using DCFH-DA and TUNEL staining. LPS and ATP induced HTR-8/SVneo cells were co-transfected with sh-PRDX6/sh-KLF9 to explore the potential regulatory effect of KLF9 on PRDX6.ResultsLPS+ATP stimulation increased KLF9 expression in the PE cell model. Specifically, reducing KLF9 levels alleviated morphological damage and enhanced proliferation, migration, and invasion in the in vitro PE cell models. Moreover, inhibiting KLF9 expression decreased protein expression of NLRP3, GSDMD-N, cleaved caspase-1, and cleaved-IL-1β, suppressing cell death in LPS+ATP-induced HTR-8/SVneo cells. Analysis of OS indicators revealed that downregulating KLF9 expression restrained intracellular ROS production, decreased MDA expression, and increased SOD and CAT levels. KLF9 regulated the transcription of PRDX6 to attenuate OS and pyroptosis. Knockdown of PRDX6 partially abolished the effect of KLF9 downregulation on OS and pyroptosis of LPS+ATP-induced HTR-8/SVneo cells, as evidenced by the inhibition of cell proliferation, migration, and invasion, as well as the enhanced activity of the NLRP3 inflammasome.ConclusionDownregulation of KLF9 enhances trophoblast cell invasion and reduces OS and NLRP3 inflammasome activation-mediated pyroptosis.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251324702"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pedunculoside inhibits cardiomyocyte inflammatory biomarkers via Nrf2/HO-1 pathway in high glucose-induced H9c2 cells and diabetic cardiomyopathy model rats.

Human & experimental toxicology Pub Date : 2025-01-01 Epub Date: 2025-03-11 DOI: 10.1177/09603271251322186

Yuanben Lu, Jianqiang Meng, Dewen Zhu, Zhenhua Jiang, Hailiang Ma

{"title":"Pedunculoside inhibits cardiomyocyte inflammatory biomarkers via Nrf2/HO-1 pathway in high glucose-induced H9c2 cells and diabetic cardiomyopathy model rats.","authors":"Yuanben Lu, Jianqiang Meng, Dewen Zhu, Zhenhua Jiang, Hailiang Ma","doi":"10.1177/09603271251322186","DOIUrl":"https://doi.org/10.1177/09603271251322186","url":null,"abstract":"IntroductionDiabetic cardiomyopathy (DCM) is a complication of diabetes mellitus (DM) that can lead to heart failure and increase the risk of mortality. Pedunculoside (PE), a novel triterpenoid saponin, exhibits anti-inflammatory and anti-oxidative stress (OS) properties. However, its role in DCM remains unexplored.MethodsDCM models were established and treated with PE or the Nrf2 inhibitor (ML385). In vitro, cell function was evaluated using CCK-8, flow cytometry, qRT-PCR, and ELISA. In vivo, fasting blood glucose and insulin levels in rats were measured. The effects of PE on DCM were assessed using HE staining, TUNEL staining, and corresponding kits. Additionally, Nrf2/HO-1 pathway proteins were analyzed by western blot.ResultsLow doses of PE (2.5, 5, 10, and 20 μM) did not affect the viability of H9c2 cells. PE (10 and 20 μM) improved cell viability and prevented apoptosis, inflammation, and OS in high glucose (HG)-stimulated H9c2 cells. PE also upregulated Nrf2 in the nucleus and enhanced HO-1 and NQO1 expression in HG-treated H9c2 cells. Furthermore, the Nrf2 inhibitor (ML385) reversed PE's protective effects on HG-induced cell injury. In vivo, PE reduced blood glucose, increased insulin, alleviated myocardial injury, inhibited apoptosis, decreased levels of inflammatory factors and OS, and upregulated Nrf2, HO-1, and NQO1 in DCM model rats.DiscussionPE alleviates DCM injury by activating the Nrf2/HO-1 pathway. These findings support the potential therapeutic application of PE in DCM.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251322186"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0