Human & experimental toxicology最新文献_第5页

Targeted inhibition of STING-TBK1 axis alleviates the hepatotoxicity of tripterygium glycosides. 靶向抑制STING-TBK1轴可减轻雷公藤苷的肝毒性。

IF 3.2

Human & experimental toxicology Pub Date : 2025-01-01 Epub Date: 2025-08-13 DOI: 10.1177/09603271251369053

Ting Yang, Tian Ma, Huanhuan Zhang, Zechen Niu, Chunzhou Cai, Dongxiao Cui

{"title":"Targeted inhibition of STING-TBK1 axis alleviates the hepatotoxicity of tripterygium glycosides.","authors":"Ting Yang, Tian Ma, Huanhuan Zhang, Zechen Niu, Chunzhou Cai, Dongxiao Cui","doi":"10.1177/09603271251369053","DOIUrl":"10.1177/09603271251369053","url":null,"abstract":"IntroductionThis study aimed to investigate the mechanisms underlying Tripterygium glycosides (TG) - induced liver injury, focusing on the role of the STING-TBK1 signaling pathway, and to evaluate the therapeutic potential of inhibiting this axis in mitigating liver damage.MethodsThe study employed two experimental approaches. First, male Balb/c mice were administered TG at doses of 13.5, 40.5, and 135 mg/kg for 3 weeks to assess dose-dependent hepatotoxicity. Liver injury was evaluated through serum ALT/AST levels, hepatic histopathology, and liver index. Immunohistochemical staining and Western blot analysis were used to examine STING expression in liver tissues and THP-1 cells. In the second approach, pharmacological inhibitors of STING and TBK1 were administered to evaluate their protective effects against TG-induced liver injury.ResultsTG induced dose-dependent liver injury and inflammatory infiltration, along with activation of the STING-TBK1 pathway in non-parenchymal cells. Inhibition of this pathway significantly attenuated hepatotoxicity, as evidenced by reduced ALT/AST levels, decreased inflammatory cytokines, and improved histopathological outcomes.DiscussionThese findings demonstrate that the STING-TBK1 axis plays a critical role in mediating TG-induced hepatotoxicity. Pharmacological inhibition of this pathway effectively alleviates TG-induced hepatotoxicity, suggesting its potential as a therapeutic target for drug-induced liver injury.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251369053"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144850094","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

Robinin attenuates cardiac hypertrophy in pulmonary heart disease by modulating SIRT1/NF-κB signaling and inhibiting oxidative stress and the NLRP3 inflammasome. Robinin通过调节SIRT1/NF-κB信号，抑制氧化应激和NLRP3炎性体，减轻肺心病心肌肥厚。

Human & experimental toxicology Pub Date : 2025-01-01 Epub Date: 2025-07-18 DOI: 10.1177/09603271251361892

Chao Wang, Lei Qin, Xinrui Zhang, Yubao Liu

{"title":"Robinin attenuates cardiac hypertrophy in pulmonary heart disease by modulating SIRT1/NF-κB signaling and inhibiting oxidative stress and the NLRP3 inflammasome.","authors":"Chao Wang, Lei Qin, Xinrui Zhang, Yubao Liu","doi":"10.1177/09603271251361892","DOIUrl":"https://doi.org/10.1177/09603271251361892","url":null,"abstract":"BackgroundRobinin possesses certain antioxidative and anti-inflammatory properties. However, its mechanisms of action in cardiac hypertrophy (CH) and fibrosis remain inadequately explored.MethodsAn in vitro model of CH was established using angiotensin II-treated rat H9c2 cardiomyocytes treated with escalating concentrations of Robinin. For the in vivo model, pulmonary heart disease-induced CH in rats was induced by chronic hypercapnia and TAC. Myocardial cell markers were evaluated through qRT-PCR, Western blotting, ELISA, cellular immunofluorescence, and HE staining. The role of SIRT1 in Robinin's effects was determined using pharmacological inhibition with SIRT1-IN-1.ResultsIn vitro, Robinin suppressed hypertrophic (ANP, BNP, β-MHC) and fibrotic markers (MyHC, Collagen I, TGF-β1) and reduced NLRP3 components (IL-1β, IL-18, ASC, Caspase-1) and oxidative stress (OS, ↓MDA, ↑SOD/HO-1/Nrf2) in a dose-dependent manner. These effects were mediated by SIRT1 upregulation and NF-κB inactivation. Crucially, SIRT1 inhibition abolished Robinin's protection against hypertrophy and inflammation. In vivo, Robinin attenuated pulmonary heart disease-induced hypertrophy, fibrosis, NLRP3 activation, and OS while restoring SIRT1/NF-κB balance.ConclusionRobinin alleviates CH in pulmonary heart disease by modulating the SIRT1/NF-κB pathway to suppress OS and NLRP3 inflammasome activation, establishing its novel therapeutic potential.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251361892"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144661409","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

Rosa roxburghii tratt juice mitigates diosbulbin B-induced hepatotoxicity through autophagy regulation. 刺梨汁通过自噬调节减轻黄黄素b诱导的肝毒性。

IF 3.2

Human & experimental toxicology Pub Date : 2025-01-01 Epub Date: 2025-08-12 DOI: 10.1177/09603271251356256

Yuhong Zhang, Xingcan Yang, Maoyuan Gong, Yang Yang, Ruobi Chen, Yuqi Li, Amin Wang, Yuyan Xu, Qibing Zeng

{"title":"Rosa roxburghii tratt juice mitigates diosbulbin B-induced hepatotoxicity through autophagy regulation.","authors":"Yuhong Zhang, Xingcan Yang, Maoyuan Gong, Yang Yang, Ruobi Chen, Yuqi Li, Amin Wang, Yuyan Xu, Qibing Zeng","doi":"10.1177/09603271251356256","DOIUrl":"https://doi.org/10.1177/09603271251356256","url":null,"abstract":"IntroductionDiosbulbin B (DB) has emerged as a potential drug for tumor treatment, but its hepatotoxicity restricts clinical use. The role of autophagy in DB-induced liver damage remains unclear. This study investigates autophagy mechanisms in DB hepatotoxicity and the protective effect of Rosa roxburghii Tratt juice (RRTJ).MethodsRats were randomized into control group, DB (12.5, 25, 50 mg/kg), RRTJ control, and RRTJ + DB (5/10 mL/kg + 50 mg/kg), and orally administered for 1 month. Hepatic superoxide dismutase (SOD)/glutathione peroxidase (GSH-Px) activities, malondialdehyde (MDA) content, serum liver function markers, and liver histopathology were assessed. Gene and protein expression levels of Beclin1, LC3B, and p62 were detected by real-time quantitative polymerase chain reaction (qPCR), immunohistochemistry, and Western blot. QPCR and immunohistochemistry evaluated the potential role of AMPK.Results25 and 50 mg/kg DB induced liver damage by reducing the levels of SOD/GSH-Px in liver tissues and increasing MDA. Resulting in elevated serum AST levels and histopathological changes such as cytoplasmic loosening, punctate necrosis in hepatocytes. DB-induced liver injury was associated with autophagic dysfunction. Compared with the control group, DB-treated rats showed upregulated expression of autophagy-related proteins Beclin1, LC3B, and p62. RRTJ inhibited DB-induced AMPK phosphorylation and reduced the expression of Beclin1, LC3B, and p62, thereby attenuating liver injury.ConclusionDB induces liver injury via autophagy dysregulation, while RRTJ alleviates damage by reducing AMPK phosphorylation to modulate autophagy, suggesting RRTJ as a potential strategy against DB-induced hepatotoxicity.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251356256"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144823487","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

Integrated gut microbiota and serum metabolomics reveal glyphosate-induced hepatic injury in mice. 综合肠道微生物群和血清代谢组学揭示草甘膦诱导的小鼠肝损伤。

Human & experimental toxicology Pub Date : 2025-01-01 Epub Date: 2025-03-11 DOI: 10.1177/09603271251326877

Gang Li, Yu Cheng, Xiaolei Yang, Zijun Chai, Zhihui Mu, Hong Chao, Hongjie Li, Yanbo Qi, Lei Qi, Jicheng Liu

{"title":"Integrated gut microbiota and serum metabolomics reveal glyphosate-induced hepatic injury in mice.","authors":"Gang Li, Yu Cheng, Xiaolei Yang, Zijun Chai, Zhihui Mu, Hong Chao, Hongjie Li, Yanbo Qi, Lei Qi, Jicheng Liu","doi":"10.1177/09603271251326877","DOIUrl":"10.1177/09603271251326877","url":null,"abstract":"IntroductionGlyphosate (GLP) is one of the most widely used herbicides in the world. However, its underlying effects on the liver remain unclear. This study aims to investigate the toxic effects and the gut microbiome- and serum metabolite-related mechanisms of GLP on the liver in mice.Methods16S rDNA sequencing and UPLC-Q-TOF-MS/MS were used to investigate the mechanisms of GLP toxicity in mice administered with 0, 50, 250 and 500 mg/kg/day GLP for 30 days.ResultsGLP induced hepatocyte edema and ballooning as well as inflammatory cell infiltration. Exposure to GLP resulted in increased levels of serum ALT, TBIL, DBIL, and GLU. Microbiota analysis at the phylum level demonstrated that the proportions of Patescibacteria decreased in the GLP-treated group. The genus-level analysis identified 11 different genera, with eight decreased and three increased in the GLP-exposed group. Metabolomics analysis of serum showed 42 differential metabolites between the GLP and control groups. The metabolic pathway enrichment analysis revealed that the pentose phosphate pathway (PPP) and pyrimidine metabolism were significantly activated. Spearman analysis showed that the changes in the differential metabolites of the PPP and pyrimidine metabolism and gut microbiota were strongly associated with the biochemical index.DiscussionIn conclusion, GLP exposure induces hepatic injury through alterations in the gut microbiome and metabolic pathways, particularly by activating the pentose phosphate pathway and pyrimidine metabolism.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251326877"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606097","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

Correction to "Corrigendum to effect of grape seed extract ondoxorubicin-induced testicular andepididymal damage in rats". 更正“葡萄籽提取物对多柔比星致大鼠睾丸和附睾损伤影响的勘误表”。

IF 3.2

Human & experimental toxicology Pub Date : 2025-01-01 Epub Date: 2025-09-04 DOI: 10.1177/09603271251374506

引用次数: 0

Thanks to Reviewers. 感谢评论者。

Human & experimental toxicology Pub Date : 2025-01-01 DOI: 10.1177/09603271251315241

引用次数: 0

Hydrogen attenuates the senescence of adipose-derived stem cells and enhances their myogenic differentiation via modulation of the PRDX6/SIRT1/PGC-1α signaling pathway. 氢通过调节PRDX6/SIRT1/PGC-1α信号通路，减缓脂肪源性干细胞的衰老，增强其肌源性分化。

IF 3.2

Human & experimental toxicology Pub Date : 2025-01-01

Pei Zhang, Yanmin Hu, Wenkang Liu, Jingcheng Wang, Yuan Liang, Wenyong Fei

{"title":"Hydrogen attenuates the senescence of adipose-derived stem cells and enhances their myogenic differentiation via modulation of the PRDX6/SIRT1/PGC-1α signaling pathway.","authors":"Pei Zhang, Yanmin Hu, Wenkang Liu, Jingcheng Wang, Yuan Liang, Wenyong Fei","doi":"","DOIUrl":"","url":null,"abstract":"IntroductionAdipose-derived mesenchymal stem cells (ADSCs) are promising candidates for regenerative therapies, but their clinical application is limited by cellular aging. This study investigated the effects of hydrogen on ADSC senescence and myogenic differentiation, along with the underlying molecular mechanisms.MethodsADSCs were treated with hydrogen gas. Senescence was assessed using β-galactosidase staining, proliferation assays, measurements of mitochondrial oxidative stress, and protein expression analysis. Differentiation capacity was evaluated through MyHC immunofluorescence, MYOD expression profiling, and quantification of myogenic regulatory factors. Additionally, the key molecular pathway of hydrogen's action was investigated by pharmacologically inhibiting PRDX6.ResultsThe findings showed that hydrogen treatment reduced senescence and increased differentiation capacity, as evidenced by higher proportions of MyHC-positive cells, increased myogenin levels, and decreased Muscle RING finger protein1 (MuRF1) expression. Molecular investigations revealed activation of the PRDX6/SIRT1/PGC-1α axis, accompanied by elevated NQO-1 expression. Importantly, pharmacological inhibition of PRDX6 largely eliminated the protective effects of hydrogen on cellular aging, disrupted differentiation, and caused mitochondrial dysfunction.DiscussionThese results suggest that hydrogen can regulate ADSC behavior via PRDX6-driven activation of SIRT1/PGC-1α signaling, offering potential approaches to improve stem cell quality for regenerative medicine.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251371685"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144983996","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

Exploring the role of rare earth elements (praseodymium, samarium, lanthanum, and terbium) and oxidative stress in polycystic ovary syndrome: A case-control study. 探讨稀土元素（镨、钐、镧和铽）和氧化应激在多囊卵巢综合征中的作用：一项病例对照研究。

Human & experimental toxicology Pub Date : 2025-01-01 Epub Date: 2025-05-16 DOI: 10.1177/09603271251342280

Manal Abudawood

{"title":"Exploring the role of rare earth elements (praseodymium, samarium, lanthanum, and terbium) and oxidative stress in polycystic ovary syndrome: A case-control study.","authors":"Manal Abudawood","doi":"10.1177/09603271251342280","DOIUrl":"https://doi.org/10.1177/09603271251342280","url":null,"abstract":"BackgroundPraseodymium (Pr), Samarium (Sm), Lanthanum (La), and Terbium (Tb) are rare earth elements (REEs) that can accumulate in the body and induce oxidative stress (OS), which may contribute to polycystic ovary syndrome (PCOS), a condition affecting 116 million women worldwide. With the increasing use of REEs, understanding their role in PCOS is crucial.DesignThis case-control study included 56 PCOS cases and 50 healthy controls, with confounding factors such as age, BMI, and hormones controlled. Inductively Coupled Plasma Mass Spectrometry (ICP-MS) was used to measure serum levels of Pr, Sm, La, and Tb, and Pearson correlation was performed to explore their relationship with oxidative stress markers such as malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD).ResultA significant increase in serum levels of Pr, Sm, La, and Tb was observed in PCOS cases compared to controls (p < 0.05). The 95% confidence intervals (CIs) for the differences in serum Pr, Sm, La, and Tb levels were [0.0008, 0.0032], [0.0002, 0.0091], [0.0019, 0.0073], and [0.0002, 0.0129], respectively. Additionally, serum levels of MDA were significantly elevated, accompanied by reduction in the antioxidant markers-GSH and SOD (p < 0.001). Elevated REE levels were positively correlated with increased MDA and negatively correlated with GSH and SOD, indicating increased oxidative stress.ConclusionThese findings suggest that oxidative stress-induced metal intoxication may play a critical role in the development of PCOS. Future studies should explore the clinical significance of REE exposure and its potential as a target for preventive strategies in PCOS management.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251342280"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083033","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

High-dose vitamin C potently induces apoptosis in acute lymphoblastic leukemia by activating ER stress response. 高剂量维生素C可通过激活内质网应激反应诱导急性淋巴细胞白血病细胞凋亡。

Human & experimental toxicology Pub Date : 2025-01-01 Epub Date: 2025-05-29 DOI: 10.1177/09603271251345656

Hui Meng Sun, Yanan Jiang, Kaiping Luo, Dong Hui Xing, Yixin Zhai, Xiang He, Wenqi Wu, Zhigang Zhao

{"title":"High-dose vitamin C potently induces apoptosis in acute lymphoblastic leukemia by activating ER stress response.","authors":"Hui Meng Sun, Yanan Jiang, Kaiping Luo, Dong Hui Xing, Yixin Zhai, Xiang He, Wenqi Wu, Zhigang Zhao","doi":"10.1177/09603271251345656","DOIUrl":"https://doi.org/10.1177/09603271251345656","url":null,"abstract":"IntroductionHigh-dose Vitamin C has shown significant anti-tumor effects in various cancers, including hematological malignancies. However, its therapeutic efficacy against acute lymphoblastic leukemia (ALL) remains underexplored.MethodsALL cell lines and normal bone marrow mononuclear cells were treated with Vitamin C to assess cell viability, apoptosis, proliferation, and cell cycle progression. Colony formation assays evaluated long-term growth. Additionally, transgenic mouse models were employed to evaluate the in vivo antitumor activity of high-dose Vitamin C in ALL. Western blotting, ROS detection 2',7'-Dichlorofluorescin diacetate (DCFH-DA), and RNA sequencing with GSEA were conducted to explore Vitamin C's mechanism of action.ResultsOur results demonstrated that high-dose Vitamin C exhibited potent cytotoxicity toward ALL cells at relatively low concentrations (200 μM) while sparing normal human bone marrow mononuclear cells even at concentrations as high as 1 mM. Vitamin C effectively inhibited ALL cell line proliferation, induced apoptosis, and disrupted cell cycle progression. We further identified that the increased expression of Solute Carrier Family 23 Member 1 (SLC23A1) in ALL cells enhanced their sensitivity to Vitamin C. In SLC23A1 knockout cells, treatment with 200 μM Vitamin C significantly restored cell viability and reduced apoptosis compared to controls. Mechanistically, high-dose Vitamin C induced apoptosis in ALL cells by activating the ER stress response through the PERK/CHOP pathway.ConclusionTaken together, our findings suggest that high-dose Vitamin C demonstrated significant anti-leukemic effects in ALL, showing cytotoxicity at 200 μM. Furthermore, SLC23A1 may serve as a potential biomarker for predicting the therapeutic response to Vitamin C treatment in ALL patients.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251345656"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183114","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

Retraction: Association of miR-9-5p and NFIC in the progression of gastric cancer. 撤回：miR-9-5p和NFIC在胃癌进展中的关联。

Human & experimental toxicology Pub Date : 2025-01-01 Epub Date: 2025-05-08 DOI: 10.1177/09603271251336600

引用次数: 0