Free Radical Research最新文献_第3页

Distal substituents effect of 4-oxo-TEMPO derivatives bearing a benzyl group at the 2-position on the reduction resistance toward ascorbate. 远端取代基2位含苄基的4-氧- tempo衍生物对抗坏血酸还原抗性的影响。

IF 3.6 3区生物学

Free Radical Research Pub Date : 2025-05-01 Epub Date: 2025-05-16 DOI: 10.1080/10715762.2025.2503839

Karin Nagahama, Toshihide Yamasaki, Kohei Sano, Takahiro Mukai

{"title":"Distal substituents effect of 4-oxo-TEMPO derivatives bearing a benzyl group at the 2-position on the reduction resistance toward ascorbate.","authors":"Karin Nagahama, Toshihide Yamasaki, Kohei Sano, Takahiro Mukai","doi":"10.1080/10715762.2025.2503839","DOIUrl":"10.1080/10715762.2025.2503839","url":null,"abstract":"Nitroxides, which have unpaired electrons, find diverse applications owing to their characteristic redox and radical chemistries. To fine-tune the properties of nitroxide compounds for various applications, we investigated the effect of distant substituents on their reactivity. We synthesized 4-oxo-2,2,6,6-tetramethylpiperidine-N-oxyl (4-oxo-TEMPO) derivatives with electron-donating or electron-withdrawing groups at the para position of the benzyl group attached to the 2-position. The reactivities of these compounds were evaluated by measuring their second-order reaction rate constants with ascorbate using ESR spectroscopy. Density functional theory (DFT) calculations for each compound revealed a correlation between the charge of the N-O moiety and the second-order reaction rate constant. Notably, even substituents positioned far from the nitroxide center significantly affected the reductive reactivity with ascorbate. These findings suggest that both proximal and distal structural modifications can be leveraged to fine-tune nitroxide properties, providing a basis for the rational design of nitroxides with tailored reactivities.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"369-376"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Edaravone inhibits neuronal ferroptosis and alleviates acute Central nervous system injury induced by diquat via enhancement of METTL14-mediated m6A methylation of Aldh1l1. 依达拉奉通过增强mettl14介导的Aldh1l1的m6A甲基化，抑制diquat诱导的神经元铁吊并减轻急性中枢神经系统损伤。

IF 3.6 3区生物学

Free Radical Research Pub Date : 2025-03-01 Epub Date: 2025-03-28 DOI: 10.1080/10715762.2025.2482774

Liaozhang Wu, Zunwei Luo, Fuli Luo, Tingting Huang, Yifang Cen, Guosheng Rao, Zhijie Zhao, Renyang Ou, Manhong Zhou

{"title":"Edaravone inhibits neuronal ferroptosis and alleviates acute Central nervous system injury induced by diquat via enhancement of METTL14-mediated m6A methylation of Aldh1l1.","authors":"Liaozhang Wu, Zunwei Luo, Fuli Luo, Tingting Huang, Yifang Cen, Guosheng Rao, Zhijie Zhao, Renyang Ou, Manhong Zhou","doi":"10.1080/10715762.2025.2482774","DOIUrl":"10.1080/10715762.2025.2482774","url":null,"abstract":"The biological effects of edaravone (Eda), a free radical scavenger, include anti-inflammatory, antioxidant, and neuroprotective qualities. Nevertheless, the function and potential mechanisms of Eda in central nervous system injury damage are still unknown. A rat model of acute diquat toxicity was constructed to observe the pathological changes in brain tissues after diquat administration. The changes of mitophagy and ferroptosis in PC12 cells were assessed to the protective activity of Eda. To assess the methylation levels of m6A RNA, the EpiQuik m6A RNA Methylation Quantification Kit was utilized. RIP, dual luciferase reporter assay and mRNA stability detection confirm the relationship between METTL14 and Aldh11l1. Knockdown and overexpression experiments were performed to determine the effects of METTL14 and Aldh1l1 on rats and PC12 cells stimulated with diquat under Eda treatment. Eda dramatically ameliorated diquat-induced central nervous system injury. Eda notably attenuated apoptosis, pro-inflammatory cytokines activation, and oxidative stress damage in diquat-induced rats. Eda significantly suppressed apoptosis, mitophagy and ferroptosis after diquat-stimulated PC12 cells. Mitophagy inhibitor Mdivi-1 reversed the induction of ferroptosis effects of diquat via decreased Fe2+ content and increased Ca2+ level. knockdown of METTL14 reversed the therapeutic effect of Eda on diquat-induced injury. Eda promoted METTL14-mediated Aldh1l1 m6A methylation and alleviates acute central nervous system injury induced by diquat in vivo and in vitro. Eda has a protective effect on diquat-induced nervous system injury, and its mechanism may be related to the activation of m6A modification of Aldh11l1 by METTL14 and the inhibition of mitophagy and.ferroptosis.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"274-288"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

FABP3 promotes cell apoptosis and oxidative stress by regulating ferroptosis in lens epithelial cells. FABP3通过调节晶状体上皮细胞铁下垂促进细胞凋亡和氧化应激。

IF 3.6 3区生物学

Free Radical Research Pub Date : 2025-03-01 Epub Date: 2025-03-13 DOI: 10.1080/10715762.2025.2475390

Qi Wang, Chunxiao Zhang, Bin Yu, Yanyan Zhang, Yuanyuan Guo

{"title":"FABP3 promotes cell apoptosis and oxidative stress by regulating ferroptosis in lens epithelial cells.","authors":"Qi Wang, Chunxiao Zhang, Bin Yu, Yanyan Zhang, Yuanyuan Guo","doi":"10.1080/10715762.2025.2475390","DOIUrl":"10.1080/10715762.2025.2475390","url":null,"abstract":"The purpose of this study is to investigate FABP3's biological function and potential mechanism in cataract. Treatment of H2O2 raised FABP3 expression. H2O2 decreased cell viability, enhanced apoptosis, promoted Bax and cleaved caspase-3 expression, inhibited Bcl-2 expression, enhanced the levels of IL-6, IL-1β, and TNF-α, raised MDA level, and decreased SOD and GSH levels in HLE-B3 cells. However, the effects of H2O2 on cell viability, apoptosis, inflammatory cytokines, and oxidative stress were reversed by FABP3 knockdown and aggravated by FABP3 overexpression. H2O2 increased the levels of lipid hydroperoxides and Fe2+, but reduced the expression of GPX4, SLC7A11, and Ferritin protein. Nevertheless, knockdown of FABP3 reversed the changes of lipid hydroperoxides, Fe2+, GPX4, SLC7A11, and Ferritin protein, and FABP3 overexpression caused the opposite results. In addition, the inhibition of FABP3 knockdown on cell apoptosis, inflammation, and oxidative stress was reversed by ferroptosis inducer (erastin), and the promotion of FABP3 overexpression on cell apoptosis, inflammation, and oxidative stress was reversed by ferroptosis inhibitor (Fer-1). Taken together, knockdown of FABP3 in lens epithelial cells treated with H2O2 restrained apoptosis, inflammation, and oxidative stress through regulating ferroptosis, suggesting that FABP3 might be a potential target for cataract treatment.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"250-261"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Luteolin protects human ARPE-19 retinal pigment epithelium cells from blue light-induced phototoxicity through activation of Nrf2/Keap1 signaling. 木犀草素通过激活Nrf2/Keap1信号通路保护人ARPE-19视网膜色素上皮细胞免受蓝光诱导的光毒性。

IF 3.6 3区生物学

Free Radical Research Pub Date : 2025-03-01 Epub Date: 2025-05-14 DOI: 10.1080/10715762.2025.2503832

Ryo Hayakawa, Takeshi Ishii, Taiki Fushimi, Yuki Kamei, Ai Yamaguchi, Kenji Sugimoto, Hitoshi Ashida, Mitsugu Akagawa

{"title":"Luteolin protects human ARPE-19 retinal pigment epithelium cells from blue light-induced phototoxicity through activation of Nrf2/Keap1 signaling.","authors":"Ryo Hayakawa, Takeshi Ishii, Taiki Fushimi, Yuki Kamei, Ai Yamaguchi, Kenji Sugimoto, Hitoshi Ashida, Mitsugu Akagawa","doi":"10.1080/10715762.2025.2503832","DOIUrl":"10.1080/10715762.2025.2503832","url":null,"abstract":"Age-related macular degeneration (AMD), a serious physical and mental health problem worldwide, is the leading cause of irreversible, severe vision impairment and loss in older people. AMD is associated with multiple risk factors, many of which are closely linked to increased oxidative stress. Some studies have suggested that long-term and excessive exposure to blue light may be a potential risk factor for the development or progression of AMD. Recently, we demonstrated that blue light irradiation caused oxidative stress in all-trans-retinal (atRAL)-exposed human ARPE-19 retinal pigment epithelium cells by generating singlet oxygen (1O2), leading to apoptotic cell death. Luteolin, a flavonoid found in various edible plants, has been reported to possess divergent health-promoting properties including anti-oxidative and chemopreventive effects by up-regulating anti-oxidative and phase II detoxifying enzymes through activation of Keap1/Nrf2 signaling. Herein, we verified the cytoprotective action of luteolin against blue light irradiation using atRAL-exposed ARPE-19 cells. Our results established that luteolin effectively prevented blue light-induced apoptosis of ARPE-19 cells by mitigating oxidative stress. We also confirmed that luteolin suppressed intracellular accumulation of 1O2 and formation of atRAL-derived lipofuscin by increased expression of heme oxygenase-1 and aldehyde dehydrogenase 1A1 through activation of Keap1/Nrf2 signaling. Furthermore, our data implied that the luteolin-provoked activation of Keap1/Nrf2 signaling might be due to covalent binding of luteolin o-quinone to the critical cysteinyl thiol in Keap1. The present results suggest that luteolin could be helpful in the prevention and amelioration of blue light-induced retinal degeneration, including AMD.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"356-368"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cigarette smoke induces endoplasmic reticulum stress-associated mucus hypersecretion via orosomucoid 1-like protein 3 in airway epithelia. 香烟烟雾通过气道上皮口躯体样蛋白1- 3诱导内质网应激相关粘液高分泌。

IF 3.6 3区生物学

Free Radical Research Pub Date : 2025-03-01 Epub Date: 2025-05-08 DOI: 10.1080/10715762.2025.2501019

Rui Chen, Yuting Cui, Mary Sau-Man Ip, Judith Choi-Wo Mak

{"title":"Cigarette smoke induces endoplasmic reticulum stress-associated mucus hypersecretion via orosomucoid 1-like protein 3 in airway epithelia.","authors":"Rui Chen, Yuting Cui, Mary Sau-Man Ip, Judith Choi-Wo Mak","doi":"10.1080/10715762.2025.2501019","DOIUrl":"10.1080/10715762.2025.2501019","url":null,"abstract":"Apart from a strong association with childhood-onset asthma, orosomucoid 1-like protein 3 (ORMDL3), an endoplasmic reticulum (ER)-localized transmembrane protein, is also linked with chronic obstructive pulmonary disease (COPD), in which cigarette smoke (CS) is the crucial risk factor. Compared to healthy subjects, COPD patients had elevated ORMDL3 mRNA in well-differentiated primary human bronchial epithelial cells (HBECs). However, its role in COPD remains understudied. We, therefore, hypothesize that ORMDL3 may play an essential role in CS-induced chronic mucus hypersecretion and inflammation via activation of specific unfolded protein response (UPR) pathways under ER stress in primary HBECs. Gene silencing using siRNA for ORMDL3 was performed in submerged culture of primary HBECs before 24-h cigarette smoke medium (CSM) exposure. The mucin, inflammatory and mitochondrial markers, and the activation of the UPR pathways were evaluated. CSM triggered significant induction of ORMDL3 expression at both mRNA and protein level, which was significantly inhibited by silencing ORMDL3. In addition, ORMDL3 knockdown inhibited CSM-induced mucin MUC5AC mRNA and release of inflammatory marker interleukin (IL)-8. Silencing ORMDL3 reduced CSM-induced ER stress via inhibiting the activating transcription factor (ATF)6 and the inositol-requiring enzyme (IRE)1 of the UPR pathways. The involvement of ORMDL3 was demonstrated in mitochondrial dynamics via fusion protein Mfn2 and mitochondrial respiration after CSM stimulation. In conclusion, ORMDL3 is an inducible gene in mediating CS-induced activation of specific ATF6 and IRE1 pathways to regulate mucus hypersecretion and inflammation. Therefore, ORMDL3 may be a promising therapeutic target to treat smoking-associated mucus hypersecretion and inflammation in COPD.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"342-355"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Reactive oxygen species-mediated cytotoxic and DNA-damaging mechanism of N⁴-hydroxycytidine, a metabolite of the COVID-19 therapeutic drug molnupiravir. n4 -羟基胞苷是COVID-19治疗药物莫诺匹拉韦的代谢物，其活性氧介导的细胞毒性和dna损伤机制

IF 3.6 3区生物学

Free Radical Research Pub Date : 2025-03-01 Epub Date: 2025-03-06 DOI: 10.1080/10715762.2025.2469738

Yurie Mori, Rinya Yogo, Hatasu Kobayashi, Hirotaka Katsuzaki, Yuichiro Hirao, Shinya Kato, Hirokazu Kotani, Shosuke Kawanishi, Mariko Murata, Shinji Oikawa

{"title":"Reactive oxygen species-mediated cytotoxic and DNA-damaging mechanism of N4-hydroxycytidine, a metabolite of the COVID-19 therapeutic drug molnupiravir.","authors":"Yurie Mori, Rinya Yogo, Hatasu Kobayashi, Hirotaka Katsuzaki, Yuichiro Hirao, Shinya Kato, Hirokazu Kotani, Shosuke Kawanishi, Mariko Murata, Shinji Oikawa","doi":"10.1080/10715762.2025.2469738","DOIUrl":"10.1080/10715762.2025.2469738","url":null,"abstract":"Molnupiravir is a prodrug of the antiviral ribonucleoside analogue N4-hydroxycytidine (NHC), for use in the treatment of coronavirus disease 2019 (COVID-19). However, it is generally considered that NHC-triphosphate is incorporated into the host genome to induce mutations. In our previous preliminary report, we proposed oxidative DNA damage by NHC via cytidine deaminase (CDA)-mediated ROS formation. In the present study, we investigated cell viability using the HL-60 human leukemia cell line and its H2O2-resistant clone, HP100 cells. The survival rate was significantly reduced in HL-60 cells treated with NHC, but not in HP100 cells. LC-MS analysis revealed that uridine formation occurred from CDA-treated NHC, suggesting that CDA metabolizes NHC to uridine and hydroxylamine. We clarified mechanisms of CDA-mediated reactive oxygen species (ROS) generation and DNA damage by NHC using isolated DNA. CDA-treated NHC induced DNA damage in the presence of Cu(II). The DNA damage was enhanced by NADH addition and piperidine treatment. CDA-treated NHC and Cu(II) caused piperidine-labile sites at thymine, cytosine, and guanine, and the DNA cleavage pattern was similar to that of hydroxylamine. Catalase and bathocuproine inhibited the DNA damage, indicating the involvement of H2O2 and Cu(I). An indicator of oxidative DNA damage, 8-oxo-7,8-dihydro-2'-deoxyguanosine formation by CDA-treated NHC, was lower under hypoxic conditions than under normal conditions. Therefore, hydroxylamine, possibly produced from NHC treated with CDA, could induce metal-dependent H2O2 generation during the redox reactions, suggesting that oxidative DNA damage induced by ROS plays an important role in molnupiravir-related cytotoxicity and mutagenicity.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"205-214"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Examining the prognostic and clinicopathological significance of GPX4 in human cancers: a meta-analysis. GPX4在人类癌症中的预后和临床病理意义：一项荟萃分析。

IF 3.6 3区生物学

Free Radical Research Pub Date : 2025-03-01 Epub Date: 2025-03-06 DOI: 10.1080/10715762.2025.2475153

Hao Wu, Xiting Liao, Wusixian Huang, Huai Hu, Lan Lan, Qianlei Yang, Yan An

{"title":"Examining the prognostic and clinicopathological significance of GPX4 in human cancers: a meta-analysis.","authors":"Hao Wu, Xiting Liao, Wusixian Huang, Huai Hu, Lan Lan, Qianlei Yang, Yan An","doi":"10.1080/10715762.2025.2475153","DOIUrl":"10.1080/10715762.2025.2475153","url":null,"abstract":"Elevated levels of the enzyme GPX4 have been detected in tumor tissues, which may play a role in cancer progression. We did a meta-analysis of eight studies encompassing 1180 individuals to evaluate the importance of GPX4 in cancer, particularly in terms of prognosis and clinicopathological characteristics. Research results indicate that higher levels of GPX4 were linked to worse overall survival (OS) (HR = 1.47 [95%CI = 1.18-1.76], p < .001). Elevated levels of GPX4 were linked to lymph node invasion (OR.69 [95% CI.44-1.10], p =.12), metastasis (OR 1.58 [95% CI.97-2.55], p =.06, p <.0001), and advanced clinical stage III-IV (OR.82 [95% CI.70-.96], p =.001). A sensitivity study revealed that the general findings were constant across all levels of impact intensity. The findings of this meta-analysis suggest that increased GPX4 levels are not only correlated with reduced overall survival rates for patients with tumors but it also offers valuable insights regarding the clinical traits of tumor malignancy and metastasis. Based on these connections, GPX4 has the potential to serve as a biomarker for tumor detection, prognosis, and targeted therapy.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"239-249"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comparison of microbubbling and conventional bubbling methods for ozonated saline solution in CKD patients: a pilot study. 微泡法与常规泡法在慢性肾病患者臭氧化盐水溶液中的比较：一项初步研究。

IF 3.6 3区生物学

Free Radical Research Pub Date : 2025-03-01 Epub Date: 2025-03-30 DOI: 10.1080/10715762.2025.2483454

Estoneck Guevara-Aguilar, Diana Moroni-González, José Carlos Jiménez-Ortega, Samuel Treviño, Victor Enrique Sarmiento-Ortega

{"title":"Comparison of microbubbling and conventional bubbling methods for ozonated saline solution in CKD patients: a pilot study.","authors":"Estoneck Guevara-Aguilar, Diana Moroni-González, José Carlos Jiménez-Ortega, Samuel Treviño, Victor Enrique Sarmiento-Ortega","doi":"10.1080/10715762.2025.2483454","DOIUrl":"10.1080/10715762.2025.2483454","url":null,"abstract":"Chronic kidney disease (CKD) is a progressive condition marked by persistent kidney damage, leading to high mortality rates and economic burden in advanced stages. Ozone therapy has emerged as a complementary alternative capable of mitigating oxidative stress involved in CKD progression. Ozonated saline solution (OSS) prepared via microbubbling offers enhanced efficacy due to greater ozone dissolution, homogeneity, and stability compared to conventional methods. This study compared the biosafety and efficacy of OSS prepared through bubbling and microbubbling methods in advanced CKD patients. In vitro, hydrogen peroxide (H2O2) concentrations were measured at various doses and times for both methods. In healthy volunteer, biosafety was assessed using TMRE and Annexin V in leukocytes. In CKD patients, TMRE, Annexin V, redox markers (catalase, superoxide dismutase, glutathione system, H2O2, lipoperoxidation), and renal function markers (urea, creatinine, glomerular filtration rate) were evaluated. Microbubbling produced lower H2O2 concentrations in vitro, depending on time and ozone dose. In vivo, both methods increased mitochondrial activity and apoptosis in CKD patient leukocytes. However, microbubbling notably enhanced antioxidant capacity, catalase and superoxide dismutase activity, and redox balance (elevated reduced-to-oxidized glutathione ratio) compared to conventional bubbling. It also showed slight improvements in serum clinical parameters. In conclusion, the microbubbling method demonstrated superior biosafety and therapeutic efficacy in advanced CKD patients, highlighting its potential as a preferred approach in ozone therapy.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"297-307"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of a novel tetrahydroxynaphthalene derivative by chemical screening with ferroptosis inhibitory activity and promising therapeutic potential. 化学筛选鉴定一种新型四羟基萘衍生物，具有抑制铁下垂活性和良好的治疗潜力。

IF 3.6 3区生物学

Free Radical Research Pub Date : 2025-03-01 Epub Date: 2025-05-01 DOI: 10.1080/10715762.2025.2497033

Takujiro Homma, Chihiro Tada, Moeka Yamauchi, Yuto Matsumoto, Shinji Matsunaga, Shuji Akai, Hiroaki Gotoh, Shuhei Tomita

{"title":"Identification of a novel tetrahydroxynaphthalene derivative by chemical screening with ferroptosis inhibitory activity and promising therapeutic potential.","authors":"Takujiro Homma, Chihiro Tada, Moeka Yamauchi, Yuto Matsumoto, Shinji Matsunaga, Shuji Akai, Hiroaki Gotoh, Shuhei Tomita","doi":"10.1080/10715762.2025.2497033","DOIUrl":"10.1080/10715762.2025.2497033","url":null,"abstract":"Hydroxyl radicals produced by the iron-mediated Fenton reaction are highly reactive, increase lipid peroxide levels, and damage cell membranes, resulting in ferroptosis, an iron-dependent form of cell death. In recent years, the role of ferroptosis in various pathological conditions has garnered interest. Because it is responsible for oxidative stress-induced organ damage, especially cell death associated with ischemia-reperfusion injury and neurological disorders, the inhibition of ferroptosis may ameliorate organ damage. Through a screen of a unique chemical compound library from Osaka University, we identified several structurally distinct compounds that were highly protective against ferroptosis in vitro. Notably, compound #562, which is a tetrahydroxynaphthalene derivative, exhibited a remarkable ability to fully rescue cells from ferroptosis at low concentrations (0.1 µM). A computational analysis revealed its structural uniqueness and high drug-likeness score, indicating its clinical potential. Along with its enhanced efficacy, this suggests that compound #562 may provide alternative modes of action or improved therapeutic potential for ferroptosis-related diseases.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"321-331"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Antioxidative activity of a novel antioxidant resorcimoline. 新型抗氧化剂间苯二胺的抗氧化活性。

IF 3.6 3区生物学

Free Radical Research Pub Date : 2025-03-01 Epub Date: 2025-05-02 DOI: 10.1080/10715762.2025.2497040

Osamu Tokumaru, Akihiro Higuchi, Takayuki Kawashima, Kazue Ogata, Kazuhiro Ueno, Takanori Inoue, Shinji Miyamoto

{"title":"Antioxidative activity of a novel antioxidant resorcimoline.","authors":"Osamu Tokumaru, Akihiro Higuchi, Takayuki Kawashima, Kazue Ogata, Kazuhiro Ueno, Takanori Inoue, Shinji Miyamoto","doi":"10.1080/10715762.2025.2497040","DOIUrl":"10.1080/10715762.2025.2497040","url":null,"abstract":"During the synthesis of a known drug, we synthesized a novel compound impromptu, which we have named resorcimoline. This compound exhibited significant antioxidative activity. In this report, we present the concentration-dependent free radical scavenging activity of resorcimoline against various free radical species. The scavenging activity of resorcimoline was evaluated against nine free radicals using electron spin resonance spectroscopy with a spin-trapping method. These free radicals were hydroxyl radical, superoxide anion, tert-butyl peroxyl radical, tert-butoxyl radical, ascorbyl free radical, singlet oxygen, nitric oxide, 2,2-diphenyl-1-picrylhydrazyl, and tyrosyl radical. Sigmoid concentration-response curves were fitted to estimate the reaction rate constants of resorcimoline for the free radicals, and these were compared with those of edaravone, the only current clinically approved free radical scavenger. The antioxidative activity of resorcimoline against lipid peroxidation within tissue was assessed using the thiobarbituric acid reactive substance (TBARS) assay. The cytotoxicity and stability of resorcimoline were also evaluated. Resorcimoline demonstrated significant concentration-dependent scavenging activity against all tested free radicals. Notably, the reaction rate constants for superoxide anion and nitric oxide were significantly higher than those of edaravone, while the rate constant for hydroxyl radical was significantly lower. The TBARS assay revealed that resorcimoline inhibited tissue lipid peroxidation in a concentration-dependent manner. Moreover, resorcimoline exhibited no cytotoxicity at concentrations up to 100 μM and remained stable at room temperature under ambient light for 7 d. These findings indicate that resorcimoline's direct free radical scavenging activity could contribute to its potential clinical antioxidative effects.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"332-341"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0