Free Radical Research最新文献_第4页

Exploring the impact of Apelin and Reactive Oxygen Species on autophagy and cell senescence in pre-eclampsia. 探讨Apelin和活性氧对子痫前期自噬和细胞衰老的影响。

IF 3.6 3区生物学

Free Radical Research Pub Date : 2025-01-01 Epub Date: 2025-01-07 DOI: 10.1080/10715762.2024.2446337

Xue Peng, Xi Tan, Li Dai, Wei Xia, Zhao Wu

引用次数: 0

Modulation of inflammatory signaling by vitamin E metabolites and its therapeutic implications. 维生素E代谢产物对炎症信号的调节及其治疗意义。

IF 3.6 3区生物学

Free Radical Research Pub Date : 2025-01-01 Epub Date: 2025-01-08 DOI: 10.1080/10715762.2024.2449457

Seher Mese-Tayfur, Tugce Demirel-Yalcıner, Anna Migni, Desirée Bartolini, Francesco Galli, Nesrin Kartal Ozer, Erdi Sozen

{"title":"Modulation of inflammatory signaling by vitamin E metabolites and its therapeutic implications.","authors":"Seher Mese-Tayfur, Tugce Demirel-Yalcıner, Anna Migni, Desirée Bartolini, Francesco Galli, Nesrin Kartal Ozer, Erdi Sozen","doi":"10.1080/10715762.2024.2449457","DOIUrl":"10.1080/10715762.2024.2449457","url":null,"abstract":"Naturally occurring vitamin E is a lipophilic plant-derived molecule corresponding to the 2 R forms of alpha-tocopherol. A series of natural analogs or tocochromanols are present in nature, including β-, γ- and δ-tocopherol (βT, γT, δT), the corresponding tocotrienols (αTE, βTE, γTE, δTE) and tocomonoenols. Differences between these analogs as lipophilic antioxidants and modulators of molecular processes suggest specific therapeutic properties against various disorders associated with acute and chronic inflammation. However, hepatic metabolism of these compounds via cytochrome P450-initiated side chain ω-oxidation involves the production of long-chain metabolites (LCMs) followed by intermediate (ICMs) and short-chain metabolites (SCMs), respectively. Despite the initial studies indicating these metabolites as catabolic-end products, recent findings identify their importance in providing biological functions. In this scope, LCMs, especially 13'-carboxychromanols (13'-COOHs), have been reported to hold stronger anti-inflammatory capacity than their unmetabolized precursors due to their ability to inhibit 5-lipoxygenase and cyclooxygenase-catalyzed eicosanoid formation, as well as their modulation of the pro-inflammatory transcriptional protein nuclear factor κB (NF-κB). Also, these LCMs have been reported to enhance detoxification and lipid metabolism pathways associated with cellular inflammation by modulating the nuclear receptors peroxisome proliferator-activated receptor-γ (PPARγ) and pregnane x receptor (PXR). These properties of LCMs will be described in this narrative review article focusing on recent information regarding their bioavailability, anti-inflammatory effects, and mechanisms of action in acute and chronic inflammatory disorders.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":"59 1","pages":"86-101"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055904","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

Apelin deficiency exacerbates cardiac injury following infarction by accelerating cardiomyocyte ferroptosis. Apelin缺乏通过加速心肌细胞铁下垂加重心肌梗死后的心脏损伤。

IF 3.6 3区生物学

Free Radical Research Pub Date : 2024-12-01 Epub Date: 2024-12-28 DOI: 10.1080/10715762.2024.2443606

Yuechu Zhao, Xiaoting Liang, Ting Li, Zhuang Shao, Zhi Cao, Yi Zeng, Xiaofei Yan, Qi Chen, Hao Zhou, Weifeng Li, Guifen Cheng, Yaping Jiang, Xin Li, Yuelin Zhang, Bei Hu

{"title":"Apelin deficiency exacerbates cardiac injury following infarction by accelerating cardiomyocyte ferroptosis.","authors":"Yuechu Zhao, Xiaoting Liang, Ting Li, Zhuang Shao, Zhi Cao, Yi Zeng, Xiaofei Yan, Qi Chen, Hao Zhou, Weifeng Li, Guifen Cheng, Yaping Jiang, Xin Li, Yuelin Zhang, Bei Hu","doi":"10.1080/10715762.2024.2443606","DOIUrl":"10.1080/10715762.2024.2443606","url":null,"abstract":"Apelin is an endogenous ligand for the Apelin receptor and is a critical protective effector in myocardial infarction (MI). Nevertheless, these protective mechanisms are not fully understood. Ferroptosis is the major driving factor of MI. This study aimed to investigate the effects and underlying regulatory mechanisms of Apelin on cardiomyocyte ferroptosis in MI. A model of MI was induced in adult C57BL/6J wild type (WT) and Apelin knockout (Apelin-/-) mice. Cardiac function was examined by echocardiography 4 weeks post-MI. RNA-seq, histochemical analyses, and Western blotting were applied to examine the effects of Apelin knockout on the transcriptome and pathological remodeling following infarction and the molecular mechanisms. Mice neonatal cardiomyocytes (NCMs) were used to establish the serum deprivation/hypoxia (SD/H) model in vitro. Compared with WT mice, Apelin-/- mice exhibited more severe impairment of cardiac function and increased fibrosis following infarction. Transcriptome and biochemical analyses revealed the involvement of ferroptosis in mediating Apelin function in MI. Ferroptosis-related proteins were significantly increased post-MI in Apelin-/- mice whereas p-AMPK was greatly decreased. Apelin treatment activated the AMPK pathway and thereby inhibited ferroptosis of NCMs induced by SD/H in vitro. These protective effects were partially reversed by AMPK inhibitor. Apelin deficiency aggravated cardiac dysfunction following infarction by activating cardiomyocyte ferroptosis via inhibition of the AMPK pathway. This offers a novel potential therapeutic target for MI treatment.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"854-867"},"PeriodicalIF":3.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893271","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

Theoretical studies on the antioxidant activity of potential marine xanthones. 关于潜在海洋氧杂蒽酮抗氧化活性的理论研究。

IF 3.6 3区生物学

Free Radical Research Pub Date : 2024-12-01 Epub Date: 2024-12-15 DOI: 10.1080/10715762.2024.2438918

Phan Thi Thuy, Nguyen Xuan Ha

{"title":"Theoretical studies on the antioxidant activity of potential marine xanthones.","authors":"Phan Thi Thuy, Nguyen Xuan Ha","doi":"10.1080/10715762.2024.2438918","DOIUrl":"10.1080/10715762.2024.2438918","url":null,"abstract":"In this study, a quantum chemical exploration was conducted to assess the antioxidant activity of xanthones isolated from marine sources, focusing on thermodynamics and kinetics within simulated physiological environments. DFT analysis revealed that xanthones such as 1,4,7-trihydroxy-6-methylxanthone (1), 1,4,5-trihydroxy-2-methylxanthone (2), arthone C (3), 2,3,4,6,8-pentahydroxy-1-methylxanthone (4), sterigmatocystin (5), oxisterigmatocystin C (6), and oxisterigmatocystin D (7) favor the SPLET pathway in water and the FHT pathway in lipid environments. The kinetic study of these xanthones reacting with the hydroperoxyl radical (HOO•) was conducted using the formal hydrogen atom transfer (FHT) mechanism and the single electron transfer (SET) mechanism. The results showed that compounds 1-4 exhibited antioxidant activities in aqueous environments surpassing that of the reference compound Trolox, with rate constants ranging from 2.02 x 105 to 9.44 x 107 M-1·s-1. In lipid environments, compounds 1 and 2 also demonstrated higher rate constants than Trolox. Additionally, molecular docking and molecular dynamics analysis suggested that xanthones 1-7 potentially inhibit the pro-oxidant effect of the Keap1 enzyme, highlighting their promise as both antiradicals and enzyme inhibitors.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"826-840"},"PeriodicalIF":3.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827681","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

New era of plasma dentistry. 等离子牙科的新时代。

IF 3.6 3区生物学

Free Radical Research Pub Date : 2024-12-01 Epub Date: 2024-12-27 DOI: 10.1080/10715762.2024.2446323

Kotaro Sato, Hiromasa Tanaka, Yasumasa Okazaki, Masaru Hori, Hideharu Hibi, Shinya Toyokuni

{"title":"New era of plasma dentistry.","authors":"Kotaro Sato, Hiromasa Tanaka, Yasumasa Okazaki, Masaru Hori, Hideharu Hibi, Shinya Toyokuni","doi":"10.1080/10715762.2024.2446323","DOIUrl":"10.1080/10715762.2024.2446323","url":null,"abstract":"Plasma, which was coined by Irving Langmuir in 1928, is the fourth physical state after the solid/liquid/gas phases. Low-temperature plasma (LTP) is a contradictory condition that involves high energy with free radicals at near-body temperatures and was developed through engineering in the 1990's. Research on LTP in engineering and medical fields has rapidly developed since the 2000's. LTP can be applied through direct or indirect exposure, and there are advantages to both methods. In the medical field, LTP has been found to exert several effects, such as wound healing, hemostasis and anticancer effects, mainly based on different levels of oxidative stress. In the dental field, studies have been performed on LTP applications for general dental procedures, such as restorative, periodontal and prosthodontic procedures, and for oral cancer treatment. Many studies have demonstrated the effectiveness of LTP. Compared with other organs, the anatomical characteristic of the oral cavity is easy direct observation, which is highly advantageous for clinical applications. Due to its good accessibility and efficiency, plasma dentistry is expected to be applied to various dental applications in clinics in the near future.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"868-874"},"PeriodicalIF":3.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876702","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

Urban aerosol particulate matter promotes cellular senescence through mitochondrial ROS-mediated Akt/Nrf2 downregulation in human retinal pigment epithelial cells. 城市气溶胶颗粒物通过线粒体ros介导的Akt/Nrf2下调促进人视网膜色素上皮细胞衰老。

IF 3.6 3区生物学

Free Radical Research Pub Date : 2024-12-01 Epub Date: 2024-12-08 DOI: 10.1080/10715762.2024.2438919

Beom Su Park, EunJin Bang, Hyun Hwangbo, Gi-Young Kim, JaeHun Cheong, Yung Hyun Choi

{"title":"Urban aerosol particulate matter promotes cellular senescence through mitochondrial ROS-mediated Akt/Nrf2 downregulation in human retinal pigment epithelial cells.","authors":"Beom Su Park, EunJin Bang, Hyun Hwangbo, Gi-Young Kim, JaeHun Cheong, Yung Hyun Choi","doi":"10.1080/10715762.2024.2438919","DOIUrl":"10.1080/10715762.2024.2438919","url":null,"abstract":"Urban aerosol particulate matter (UPM) is widespread in the environment, and its concentration continues to increase. Several recent studies have reported that UPM results in premature cellular senescence, but few studies have investigated the molecular basis of UPM-induced senescence in retinal pigment epithelial (RPE) cells. In this study, we primarily evaluated UPM-induced premature senescence and the protective function of nuclear factor erythroid 2-related factor 2 (Nrf2) in human RPE ARPE-19 cells. The findings indicated that UPM exposure substantially induced premature cellular senescence in ARPE-19 cells, as observed by increased β-galactosidase activity, expression levels of senescence-associated marker proteins, and senescence-associated phenotypes. Such UPM-induced senescence is associated with mitochondrial oxidative stress-mediated phosphatidylinositol 3'-kinase/Akt/Nrf2 downregulation. Sulforaphane-mediated Nrf2 activation Sulforaphane-mediated upregulation of phosphorylated Nrf2 suppressed the decrease in its target antioxidant gene, NAD(P)H quinone oxidoreductase 1, under UPM, which notably prevented ARPE-19 cells from UPM-induced cellular senescence. By contrast, Nrf2 knockdown exacerbated cellular senescence and promoted oxidative stress. Collectively, our results demonstrate the regulatory role of Nrf2 in UPM-induced senescence of RPE cells and suggest that Nrf2 is a potential molecular target.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"841-853"},"PeriodicalIF":3.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794468","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

Accumulation of polyunsaturated lipids fuels ferroptosis to promote liver failure after extended hepatectomy in mice. 多不饱和脂质的积累助长了铁变态反应，从而导致小鼠肝切除术后肝功能衰竭。

IF 3.6 3区生物学

Free Radical Research Pub Date : 2024-11-01 Epub Date: 2024-11-08 DOI: 10.1080/10715762.2024.2423691

Can Huang, Jian Gan, Xiangyue Mo, Qingping Li, Leyi Liao, Biao Wang, Xianqiu Wu, Hanbiao Liang, Chen Xie, Tianzhou Peng, Yang Lei, Baoxiong Zhuang, Minghui Zeng, Yonghong Peng, Yisi Chen, Cuiting Liu, Jie Zhou, Kai Wang, Chuanjiang Li

{"title":"Accumulation of polyunsaturated lipids fuels ferroptosis to promote liver failure after extended hepatectomy in mice.","authors":"Can Huang, Jian Gan, Xiangyue Mo, Qingping Li, Leyi Liao, Biao Wang, Xianqiu Wu, Hanbiao Liang, Chen Xie, Tianzhou Peng, Yang Lei, Baoxiong Zhuang, Minghui Zeng, Yonghong Peng, Yisi Chen, Cuiting Liu, Jie Zhou, Kai Wang, Chuanjiang Li","doi":"10.1080/10715762.2024.2423691","DOIUrl":"10.1080/10715762.2024.2423691","url":null,"abstract":"Background: Post-hepatectomy liver failure (PHLF) is a fatal complication of hepatectomy. However, the mechanism of hepatocyte injury in PHLF remains elusive.Methods: PHLF was induced by extended 86% hepatectomy (eHx) in mice. Lipidomics was performed to investigate the eHx-induced lipid alteration in the residual liver. Ferroptosis was assessed to screen the hepatocyte injury induced by eHx. The therapeutic effects of ferrostatin-1 (Fer-1) on PHLF were evaluated.Results: PHLF was induced by eHx with elevation in markers of hepatocyte injury and mortality in mice within 48 h after surgery. eHx-induced hepatocyte injury was manifested by hepatocyte enlargement and hepatocyte death with glycogen depletion and lipid accumulation. Lipidomics revealed that eHx induced the accumulation of ferroptosis-favored polyunsaturated lipids. Ferroptosis was found to mediate the eHx-induced hepatocyte death in the residual liver during the development of PHLF. Fer-1 could attenuate the eHx-induced ferroptotic hepatocyte death and PHLF in mice.Conclusions: Ferroptosis partly mediates the eHx-induced hepatocyte injury during the development of PHLF. Accumulation of polyunsaturated lipids in hepatocytes may promote eHx-induced ferroptosis, and targeting lipid peroxidation is a potential therapeutic strategy for PHLF.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"733-747"},"PeriodicalIF":3.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603925","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

The impact of hyperbaric oxygen therapy on the redox balance of patients with diabetic foot syndrome. 高压氧疗法对糖尿病足综合征患者氧化还原平衡的影响。

IF 3.6 3区生物学

Free Radical Research Pub Date : 2024-11-01 Epub Date: 2024-10-19 DOI: 10.1080/10715762.2024.2417286

Paweł Sutkowy, Jarosław Paprocki, Jacek Piechocki, Alina Woźniak

{"title":"The impact of hyperbaric oxygen therapy on the redox balance of patients with diabetic foot syndrome.","authors":"Paweł Sutkowy, Jarosław Paprocki, Jacek Piechocki, Alina Woźniak","doi":"10.1080/10715762.2024.2417286","DOIUrl":"10.1080/10715762.2024.2417286","url":null,"abstract":"Diabetic foot wounds associated with oxidative stress are treated with hyperbaric oxygen (HBO), but that may also induce the stress itself; therefore, we studied the effect of HBO treatments on the oxidant-antioxidant balance in the venous blood of patients with diabetic foot syndrome. In addition, blood counts were also examined. 14 male patients (24-74 years), at risk of lower limb amputation were treated with 30 HBO procedures (60 min of the inhalation of pure oxygen at a pressure of 2.5 atm per day, 5 days a week). The control group consisted of 29 healthy male volunteers aged 25-69 years. No members of the group had been subjected to HBO therapy previously (ClinicalTrials.gov, no. NCT06401941). The analyzed redox parameters did not change during the experiment in the patients (p > 0.05). The concentration of thiobarbituric acid reactive substances (TBARS) in the plasma was higher in the patients before the first and after the thirtieth HBO treatments when compared to the control group. In contrast, the TBARS concentration in erythrocytes was lower in the patients after the first treatment vs. the controls. Moreover, the higher activity of catalase in the patients' erythrocytes was noted before the therapy and after the first and last treatments compared to the controls. HBO therapy increased the percentage of monocytes and platelet volume, but it decreased the volume of platelets in the patients' blood. HBO therapy does not affect the oxidant-antioxidant balance disturbed in diabetic foot patients.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"723-732"},"PeriodicalIF":3.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461847","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

Ferritin with methylglyoxal produces reactive oxygen species but remains functional. 含有甲基乙二醛的铁蛋白会产生活性氧，但仍能发挥作用。

IF 3.6 3区生物学

Free Radical Research Pub Date : 2024-11-01 Epub Date: 2024-11-07 DOI: 10.1080/10715762.2024.2417281

Adriana Rybnikářová, Richard Buchal, Jan Pláteník

{"title":"Ferritin with methylglyoxal produces reactive oxygen species but remains functional.","authors":"Adriana Rybnikářová, Richard Buchal, Jan Pláteník","doi":"10.1080/10715762.2024.2417281","DOIUrl":"10.1080/10715762.2024.2417281","url":null,"abstract":"Iron is necessary for life, but the simultaneous iron-catalyzed formation of reactive oxygen species (ROS) is involved in pathogenesis of many diseases. One of them is diabetes mellitus, a widespread disease with severe long-term complications, including neuropathy, retinopathy, and nephropathy. Much evidence points to methylglyoxal, a potent glycating agent, as the key mediator of diabetic complications. In diabetes, there is also a peculiar dysregulation of iron homeostasis, leading to an expansion of redox-active iron. This in vitro study focuses on the interaction of methylglyoxal with ferritin, which is the main cellular protein for iron storage. Methylglyoxal effectively liberates iron from horse spleen ferritin, as well as synthetic iron cores; in both cases, it is partially mediated by superoxide. The interaction of methylglyoxal with ferritin increases the production of hydrogen peroxide, much above the generation of peroxide by methylglyoxal alone, in an iron-dependent manner. Glycation with methylglyoxal results in structural changes in ferritin. All of these findings can be demonstrated with pathophysiologically relevant (submillimolar) methylglyoxal concentrations. However, the rate of iron release by ascorbate, the ferroxidase activity, or the diameter of gated pores even in intensely glycated ferritin is not altered. In conclusion, although the functional features of ferritin resist alterations due to glycation, the interaction of methylglyoxal with ferritin liberates iron and markedly increases ROS production, both of which could enhance oxidative stress in vivo. Our findings may have implications for the pathogenesis of long-term diabetic complications, as well as for the use of ferritin as a nanocarrier in chemotherapy.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"702-722"},"PeriodicalIF":3.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603927","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

Metformin suppresses metabolic dysfunction-associated fatty liver disease by ferroptosis and apoptosis via activation of oxidative stress. 二甲双胍通过激活氧化应激，抑制铁凋亡和细胞凋亡，从而抑制代谢功能障碍相关性脂肪肝。

IF 3.6 3区生物学

Free Radical Research Pub Date : 2024-11-01 Epub Date: 2024-10-18 DOI: 10.1080/10715762.2024.2417279

Zhiyu Li, Chao Cui, Liang Xu, Mingfeng Ding, Yinghui Wang

{"title":"Metformin suppresses metabolic dysfunction-associated fatty liver disease by ferroptosis and apoptosis via activation of oxidative stress.","authors":"Zhiyu Li, Chao Cui, Liang Xu, Mingfeng Ding, Yinghui Wang","doi":"10.1080/10715762.2024.2417279","DOIUrl":"10.1080/10715762.2024.2417279","url":null,"abstract":"Metformin is known for its antioxidant properties and ability to ameliorate metabolic dysfunction-associated fatty liver disease (MAFLD) and is the focus of this study. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is linked to MAFLD risk. This study investigated the effects of metformin on ferroptosis in free fatty acid (FFA)-treated Huh7 hepatoma cells and its association with MAFLD risk. Using Western blot, immunofluorescence, and ELISA, this study revealed that FFA treatment led to increased intracellular fat and iron accumulation, heightened Lp-PLA2 expression, reduced levels of the cysteine transporter SLC7A11 and glutathione peroxidase 4 (GPX4), altered glutathione (GSH)/oxidized glutathione (GSSG) ratios, generation of reactive oxygen species (ROS), and initiation of lipid peroxidation, which ultimately resulted in cell ferroptosis. Importantly, metformin reversed FFA-induced iron accumulation, and this effect was attenuated by ferrostatin-1 but enhanced by erastin, RSL3, and si-GPX4. Additionally, metformin activated antioxidant and antiapoptotic mechanisms, which reduced lipid peroxidation and suppressed Lp-PLA2 expression in FFA-treated Huh7 cells. In conclusion, our findings indicate that metformin may protect against MAFLD by inhibiting iron accumulation and Lp-PLA2 expression through the ROS, ferroptosis, and apoptosis signaling pathways. This study highlights potential therapeutic strategies for managing MAFLD-related risks and emphasizes the diverse roles of metformin in maintaining hepatocyte balance.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"686-701"},"PeriodicalIF":3.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461846","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