Toxicology Research最新文献

The ameliorative effects of metformin and taurine against thioacetamide hepatotoxicity in rats. 二甲双胍和牛磺酸对大鼠硫乙酰胺肝毒性的改善作用。

IF 2.2 4区医学

Toxicology Research Pub Date : 2025-06-09 eCollection Date: 2025-06-01 DOI: 10.1093/toxres/tfaf076

Sherouk S Badawy, Mohammad M Mashaly, A F Abdel-Aziz, Mai M Madkour

{"title":"The ameliorative effects of metformin and taurine against thioacetamide hepatotoxicity in rats.","authors":"Sherouk S Badawy, Mohammad M Mashaly, A F Abdel-Aziz, Mai M Madkour","doi":"10.1093/toxres/tfaf076","DOIUrl":"10.1093/toxres/tfaf076","url":null,"abstract":"The main objective of this research was to investigate the therapeutic, anti-inflammatory, and histological effects of metformin and taurine, both alone and in combination, against thioacetamide (TAA)-induced hepatotoxicity in rats. The study included forty adult male Swiss albino rats, which were divided into five groups: Group I provided the control group. Group II (TAA group) rats received injections of TAA (200 mg/kg b.wt /3 times/week, i.p.) for six weeks. Group III (TAA + metformin) rats received administration of metformin (200 mg/kg/day, p.o.) for five weeks. Group IV (TAA + taurine) rats received injections of taurine (100 mg/kg/day, i.p.) for five weeks, while Group V (TAA + metformin + taurine) rats received daily intraperitoneal injections and oral administration of the medication for five weeks. Inflammation and changes in liver function are hallmarks of TAA-induced hepatotoxicity. Our findings demonstrated that the greatly improved liver dysfunction might be attributed to the effects of metformin and taurine. Furthermore, a combination of metformin and taurine markedly inhibited inflammatory responses, as indicated by the decreased levels of the inflammatory cytokine IL-6. The biochemical results were confirmed by the histological analyses of the liver tissues. Post-treatments of metformin and taurine might have crucial potential and synergistic effects against TAA-induced hepatotoxicity.","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 3","pages":"tfaf076"},"PeriodicalIF":2.2,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12146511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hepatoprotective mechanisms of ginkgo-Biloba and dandelion extracts: antioxidant activity and modulation of TNF-α and P53 pathways in Thioacetamide-induced liver injury. 银杏叶和蒲公英提取物的肝保护机制：硫代乙酰胺诱导肝损伤的抗氧化活性和TNF-α和P53通路的调节。

IF 2.2 4区医学

Toxicology Research Pub Date : 2025-06-08 eCollection Date: 2025-06-01 DOI: 10.1093/toxres/tfaf075

Heba M Shaaban, El-Sayed E Mehana, Samah S Oda, Hossam G Tohamy, Dina R Gad El-Karim, Mustafa Shukry

{"title":"Hepatoprotective mechanisms of ginkgo-Biloba and dandelion extracts: antioxidant activity and modulation of TNF-α and P53 pathways in Thioacetamide-induced liver injury.","authors":"Heba M Shaaban, El-Sayed E Mehana, Samah S Oda, Hossam G Tohamy, Dina R Gad El-Karim, Mustafa Shukry","doi":"10.1093/toxres/tfaf075","DOIUrl":"10.1093/toxres/tfaf075","url":null,"abstract":"Liver injuries, especially those induced by chemical toxins and pharmaceuticals, are increasingly prevalent. This study evaluated the hepatoprotective effects of Ginkgo biloba and dandelion extracts in a rat model of thioacetamide (TAA)-induced liver injury. Twenty-eight male albino rats were randomly assigned to four groups: control, TAA-treated, TAA plus G. biloba (100 mg/kg), and TAA plus dandelion (500 mg/kg). TAA administration over eight weeks significantly elevated serum liver enzymes (AST, ALT, ALP, and GGT), bilirubin, cholesterol, and triglycerides (P < 0.05) while significantly reducing total protein and albumin levels (P < 0.05). TAA also induced oxidative stress, evident by increased hepatic malondialdehyde and reduced glutathione levels (P < 0.05). Co-treatment with G. biloba or dandelion extracts significantly ameliorated these biochemical alterations (P < 0.05), with G. biloba demonstrating slightly stronger effects. Histopathological examination showed reduced necrosis, fibrosis, and inflammatory cell infiltration in treated groups. Immunohistochemical analysis confirmed decreased expression of TNF-α and P53 proteins (P < 0.05), indicating anti-inflammatory and anti-apoptotic properties. These findings suggest that G. biloba and dandelion extracts confer protective effects against TAA-induced liver damage through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms.","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 3","pages":"tfaf075"},"PeriodicalIF":2.2,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12145877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144256870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Use of new approach methodology for hepatic safety assessment of covalent inhibitor drug candidates. 应用新方法评价共价抑制剂候选药物的肝脏安全性。

IF 2.2 4区医学

Toxicology Research Pub Date : 2025-05-25 eCollection Date: 2025-06-01 DOI: 10.1093/toxres/tfaf054

Sara Amberntsson, Alison J Foster, Bhavik Chouhan, Stephen Wilkinson, Stephanie Harlfinger, Graham Smith, Jason G Kettle, Michael Niedbala, Stefan Kavanagh, Dominic P Williams

{"title":"Use of new approach methodology for hepatic safety assessment of covalent inhibitor drug candidates.","authors":"Sara Amberntsson, Alison J Foster, Bhavik Chouhan, Stephen Wilkinson, Stephanie Harlfinger, Graham Smith, Jason G Kettle, Michael Niedbala, Stefan Kavanagh, Dominic P Williams","doi":"10.1093/toxres/tfaf054","DOIUrl":"10.1093/toxres/tfaf054","url":null,"abstract":"Interest in inhibiting target proteins through covalent binding mechanisms has increased in the last decade due to the potential for beneficial pharmacological properties. However, the inherent targeted covalent inhibitor (TCI) adverse off-target reactivity risk requires a mitigation strategy early during drug discovery. The aim of this research was to design a pre-clinical hepatic safety assessment strategy for TCIs considering risk associated with electrophilic warhead reactivity and reactive metabolites formation at clinically-relevant plasma concentrations. The mitigation strategy was applied to compound 35, a potent irreversible inhibitor to KRASG12C. Drug induced liver injury was assessed in primary human hepatocyte spheroids. GSH and ATP depletion were investigated for compound 35 and 6 other marketed TCIs containing an acrylamide warhead which binds irreversibly to cysteine-containing target proteins. None of the TCIs showed GSH depletion prior to ATP depletion after 7-days exposure, suggesting that GSH depletion was not driving cytotoxicity in the spheroids. The calculated hepatotoxicity margin towards plasma exposure of 2.5 for compound 35 was found to be in the same range as for the two KRASG12Cinhibitors adagrasib and sotorasib, with clinically reported treatment-related adverse aminotransferase elevations leading to dose modifications. The safety evaluation reported here suggests no negative discrepancy in liver toxicity for compound 35 versus similar approved TCI's. Finally, the risk associated with detected oxidative metabolites was further mitigated as the pan-CYP450 inhibitor 1-aminobenzotriazole (ABT) had no effect on the cytotoxicity response following incubation of compound 35 in the presence and absence of ABT.","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 3","pages":"tfaf054"},"PeriodicalIF":2.2,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Protective effects of apricot kernel oil and metformin against BPA-induced ovarian toxicity in rat models of polycystic ovary syndrome: insights into PI3K/AKT and mitochondrial apoptosis pathways. 杏仁油和二甲双胍对bpa诱导的多囊卵巢综合征大鼠卵巢毒性的保护作用：对PI3K/AKT和线粒体凋亡途径的见解

IF 2.2 4区医学

Toxicology Research Pub Date : 2025-05-25 eCollection Date: 2025-06-01 DOI: 10.1093/toxres/tfaf071

Xuejuan Jiao, Qianqian Zhang, Guoliu Ye, Fang Xing, Dongmei Xie, Liqun Wang

{"title":"Protective effects of apricot kernel oil and metformin against BPA-induced ovarian toxicity in rat models of polycystic ovary syndrome: insights into PI3K/AKT and mitochondrial apoptosis pathways.","authors":"Xuejuan Jiao, Qianqian Zhang, Guoliu Ye, Fang Xing, Dongmei Xie, Liqun Wang","doi":"10.1093/toxres/tfaf071","DOIUrl":"10.1093/toxres/tfaf071","url":null,"abstract":"In this study, the therapeutic synergistic effects of metformin (MET) and Apricot Kernel Oil (AKO) were investigated in an animal model of bisphenol A (BPA)-induced polycystic ovary syndrome (PCOS). BPA disrupts endocrine functions and induces oxidative stress in ovarian tissues, leading to PCOS. AKO and MET target underlying mechanisms associated with PCOS, particularly those related to insulin resistance and oxidative stress, which are critical in the pathology of this condition. Antioxidant activities, total phenolic, and flavonoid contents of AKO were performed. The AKO underwent liquid chromatographic-electrospray ionization tandem mass-spectrometric (LC-ESI-MS/MS) analysis after acetonitrile treatment. PCOS was induced in adult Wistar rats by administering BPA. After 60 days, the 70 rats were divided into seven groups (n = 10/group): Normal, PCOS, MET, AKO, and co-treatment with MET and AKO. On the 22ndday of the study, serum catalase, glutathione peroxidase, superoxide dismutase activity, LH, FSH, progesterone, estrogen, and testosterone hormones alongside inflammatory cytokines (TNF-a, IL-6, CRP, and IL-1β) and nitric oxide levels were measured. Ovarian tissues were isolated for measurements of ferric reducing ability of plasma and thiobarbituric acid reactive substances levels. The expression of genes and proteins related to mitochondrial and PI3K/AKT pathways was analyzed. The results demonstrated that AKO, in synergy with MET, modulated hormone levels, reduced pro-inflammatory cytokines, and enhanced antioxidant properties. AKO, in combination with MET modulated apoptosis via mitochondrial and PI3K/AKT pathways. These findings suggest that AKO holds promise as a potential therapeutic option for women with ovulation disorders, particularly those affected by bisphenol A-induced PCOS.","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 3","pages":"tfaf071"},"PeriodicalIF":2.2,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chaperone mediated autophagy modulates microglia polarization and inflammation via LAMP2A in ischemia induced spinal cord injury. 伴蛋白介导的自噬通过LAMP2A调节缺血脊髓损伤中的小胶质细胞极化和炎症。

IF 2.2 4区医学

Toxicology Research Pub Date : 2025-04-29 eCollection Date: 2025-04-01 DOI: 10.1093/toxres/tfaf061

Dan Fu, Ziyou Li, Huafeng Feng, Fangling Fan, Wang Zhang, Liang He

{"title":"Chaperone mediated autophagy modulates microglia polarization and inflammation via LAMP2A in ischemia induced spinal cord injury.","authors":"Dan Fu, Ziyou Li, Huafeng Feng, Fangling Fan, Wang Zhang, Liang He","doi":"10.1093/toxres/tfaf061","DOIUrl":"https://doi.org/10.1093/toxres/tfaf061","url":null,"abstract":"Spinal cord injury (SCI)-induced ischemic delayed paralysis is one of the most serious side effects of aneurysms surgeries. Recent studies prove that the activation of autophagy, including macroautophagy and micro-autophagy pathways, occur during SCI-induced brain neuron damage. However, the role of chaperone mediated autophagy (CMA) during SCI remains to be unveiled. In the present work, rat model of delayed paralysis after aneurysms operation and adenovrius induced LAMP2A knockdown in microglia cells were applied in the present work to investigate the involvement of LAMP2A-mediated CMA in the aneurysm operation related SCI and delayed paralysis. The results showed that LAMP2A was upregulated in the SCI procedure, and contributed to neuron death and pro-inflammation perturbation via inducing iNOS+ polarization in microgila. We additionally observed that knockdown of LAMP2A resulted in the shift of microglia from iNOS+ to ARG1+ phenotype, as well as alleviated neuron damage during SCI. Furthermore, the analysis of BBB score, the result of immunohistological staining, and protein detection confirmed the activation of LAMP2A-mediated CMA activation and its interaction with NF-κB signaling, which leads to neuron death and motor function loss. These results prove that LAMP2A-mediated CMA contributes to the upregulation of pro-inflammatory cytokines and results in cell death in neurons during ischemic delayed paralysis via activating NF-κB signaling. Inhibition of LAMP2A promotes neurons survival during ischemic delayed paralysis.","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 2","pages":"tfaf061"},"PeriodicalIF":2.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12038812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

FTO-mediated m6A demethylation of KLF4 promotes the proliferation and collagen deposition of keloid fibroblasts. fto介导的KLF4的m6A去甲基化促进瘢痕疙瘩成纤维细胞的增殖和胶原沉积。

IF 2.2 4区医学

Toxicology Research Pub Date : 2025-04-26 eCollection Date: 2025-04-01 DOI: 10.1093/toxres/tfaf058

Yanqi Li, Wanchao Wang, Yuge Wang, Hongmei Ai

{"title":"FTO-mediated m6A demethylation of KLF4 promotes the proliferation and collagen deposition of keloid fibroblasts.","authors":"Yanqi Li, Wanchao Wang, Yuge Wang, Hongmei Ai","doi":"10.1093/toxres/tfaf058","DOIUrl":"https://doi.org/10.1093/toxres/tfaf058","url":null,"abstract":"This study aims to elucidate the molecular mechanism mechanism by which FTO affects fibroblast proliferation and collagen deposition in keloids. Human keloid fibroblasts (KFs) and normal fibroblasts were cultured in vitro. FTO expression was silenced in KFs, and cell viability and proliferation were evaluated via CCK-8 and clone formation assays. FTO, KLF4, and MC1R expressions were quantified via qRT-PCR, while the protein levels of FTO, KLF4, MC1R, Collagen I, and Collagen III were determined by Western blot. The m6A RNA methylation status of total RNA was evaluated using the EpiQuik m6A RNA Methylation Quantification Kit. Post-actinomycin D treatment, the stability of KLF4 mRNA and its m6A modification level were measured. ChIP and dual-luciferase reporter assays confirmed the binding between KLF4 and MC1R promoter. KFs presented with significantly enhanced proliferation and collagen deposition, correlating with elevated FTO expression. Silence of FTO repressed the proliferation and collagen deposition of KFs, and elevated the m6A levels of total RNA and KLF4 mRNA in KFs, resulting in enhanced KLF4 mRNA stability and expression. KLF4 bound to the MC1R promoter and promoted MC1R expression. In conclusion, FTO represses KLF4 expression by removing m6A modification and further diminishes MC1R expression, thereby facilitating KF proliferation and collagen deposition.","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 2","pages":"tfaf058"},"PeriodicalIF":2.2,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12031721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Catechin designates individual and co-adjuvant antiproliferative effects with docetaxel in prostate cancer cell models. 儿茶素与多西紫杉醇在前列腺癌细胞模型中的单独和辅助抗增殖作用。

IF 2.2 4区医学

Toxicology Research Pub Date : 2025-04-24 eCollection Date: 2025-04-01 DOI: 10.1093/toxres/tfaf057

Eman E El Nahass, Safaa I Abou Eldahab, Elsayed I Salim

{"title":"Catechin designates individual and co-adjuvant antiproliferative effects with docetaxel in prostate cancer cell models.","authors":"Eman E El Nahass, Safaa I Abou Eldahab, Elsayed I Salim","doi":"10.1093/toxres/tfaf057","DOIUrl":"https://doi.org/10.1093/toxres/tfaf057","url":null,"abstract":"The current study examined the potential therapeutic advantages of catechin, either alone or in combination with docetaxel (DTX), against PC-3 prostate cancer cells. Following the MTT assay's determination of the IC50 concentrations, the cell lines were subjected to 48 h of treatment in the following protocol: untreated PC-3 control cells, docetaxel treatment, catechin (Cat) treatment, and DTX + Cat therapy at a ratio of 1:1. Treatments with DTX and Cat significantly decreased the number of viable cells in PC-3 cells in a dose-dependent manner. Additionally, the combo treatments caused the highest cytotoxicity compared with the other treatments. Also, when DTX and Cat were combined, they caused a significant synergistic effect (CI < 1) (combination index < 1). Furthermore, it was demonstrated that all treatments increased the expression of BAX, Caspase-3, and P21 mRNA in PC-3 cells while decreasing that of BCL-2 mRNA. The highest proportion of overexpression was observed in the combo therapy. A greater proportion of early and late apoptotic cells were caused by the combined treatment than by > DTX > Cat, according to flow cytometry. DNA damage in PC-3 cells was detected using the comet assay, and values of DNA tail, tail length, and tail moment increased considerably with increasing treatment dose. According to this study, Cat is effective against PC-3 cells when used in conjunction with DTX; by causing apoptosis, it enhances DTX's chemotherapeutic capability in cancerous cells.","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 2","pages":"tfaf057"},"PeriodicalIF":2.2,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12021262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Reproductive and developmental toxicology of nitrosamines. 亚硝胺的生殖和发育毒理学。

IF 2.2 4区医学

Toxicology Research Pub Date : 2025-04-16 eCollection Date: 2025-04-01 DOI: 10.1093/toxres/tfaf051

Juan Liu, Wei Xu, Yi Liu, Qi Zhang

{"title":"Reproductive and developmental toxicology of nitrosamines.","authors":"Juan Liu, Wei Xu, Yi Liu, Qi Zhang","doi":"10.1093/toxres/tfaf051","DOIUrl":"https://doi.org/10.1093/toxres/tfaf051","url":null,"abstract":"With the development of science and technology and the acceleration of industrialization, environmental pollution is becoming more and more serious, and the global fertility rate is decreasing every year, which makes people pay more attention to reproductive health. Nitrosamines are a kind of easy to contact food pollutants, widely exist in pickled food (10.2-14.8 mg/kg) and contaminated water sources (10-150 ng/L), etc. They have been confirmed to be carcinogenic, but the reproductive and developmental toxic effects of nitrosamines have not been systematically reported. Based on relevant researches, the classification, distribution and metabolism kinetics of nitrosamines were summarized in this review. In addition, nitrosamines can inhibit testosterone synthesis (Leydig cells) and spermatogenesis (spermatogenic cells) in F0 male, and reduce ovary functions in F0 female, finally induce parental reproductive toxic effects. Meanwhile, the effects of parental (including maternal pregnancy, paternal) nitrosamine exposure on offspring development (such as cancer susceptibility) and related research deficiencies were summarized. To sum up, this paper systematically reviewed the reproductive and developmental toxic effects caused by exposure to nitrosamines, enabling people to fully understand the negative effects of nitrosamines on the body, so as to effectively avoid and reduce intake in daily life, and at the same time provide a theoretical and literature basis for guiding the healthy life and maintaining fertility.","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 2","pages":"tfaf051"},"PeriodicalIF":2.2,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12001771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ellagic acid alleviates PM_2.5-induced senescence of lung epithelial cells by mediating autophagy. 鞣花酸通过介导自噬减轻pm2.5诱导的肺上皮细胞衰老。

IF 2.2 4区医学

Toxicology Research Pub Date : 2025-04-16 eCollection Date: 2025-04-01 DOI: 10.1093/toxres/tfaf055

Yuqi Tong, Yanping Lu, Yaqi Li, Jiaquan Ding, Chenxi Yan, Zhihui Deng, Jiekang Chen, Zhaohui Zhang

{"title":"Ellagic acid alleviates PM2.5-induced senescence of lung epithelial cells by mediating autophagy.","authors":"Yuqi Tong, Yanping Lu, Yaqi Li, Jiaquan Ding, Chenxi Yan, Zhihui Deng, Jiekang Chen, Zhaohui Zhang","doi":"10.1093/toxres/tfaf055","DOIUrl":"https://doi.org/10.1093/toxres/tfaf055","url":null,"abstract":"Fine particulate matter (PM2.5) exposure is significantly linked to lung epithelial cell senescence, and autophagy dysfunction being a key contributor to the aging process. Although the anti-aging properties of ellagic acid (EA) are well-documented, its specific protective effect on PM2.5-induced lung epithelial cell senescence still needs to be studied in depth. To investigate the impacts of PM2.5 on autophagy and senescence in lung epithelial cells, 16HBE and A549 cells were exposed to PM2.5 suspension. Additionally, to explore the potential intervention effect of EA, cells were pretreated with EA before exposure to PM2.5 suspension. Cell morphology, proliferation, senescence-related markers, senescence-associated secretory phenotype (SASP), and autophagy-related markers were then assessed. Our results showed that the proliferation of 16HBE and A549 cells were inhibited and autophagy dysfunction and senescence were induced under PM2.5 exposure. However, pretreatment with EA can significantly improve the obstruction of autophagy flux caused by PM2.5, thereby effectively alleviating cell senescence. This study reveals the mechanism by which PM2.5 induces senescence in lung epithelial cells and confirms the protective role of ellagic acid in this process.","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 2","pages":"tfaf055"},"PeriodicalIF":2.2,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12001767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Toxic endpoints or ubiquitous expression? 有毒终点还是无处不在的表达？

IF 2.2 4区医学

Toxicology Research Pub Date : 2025-04-14 eCollection Date: 2025-04-01 DOI: 10.1093/toxres/tfaf052

Rajesh Pamanji, Gisha Sivan

引用次数: 0