FREE RADICAL BIOLOGY AND MEDICINE
·
2025
·
IF 8.2
Tongwang Luo,Shengzhe Song,Shujie Wang,Sheng Jiang,Bin Zhou,Quanjiang Song,Lingjun Shen,Xiaodu Wang,Houhui Song,Chunyan Shao
Cadmium (Cd), a pervasive environmental toxicant, poses significant threats to human and animal health through multi-organ toxicity. While ferroptosis has been implicated in Cd-induced pathologies, the molecular mechanisms underlying Cd-mediated nephrotoxicity remain poorly understood. This study elucidates the ferroptosis pathway in CdCl 2 -exposed PK-15 cells and murine kidney, characterized by iron overload, lipid peroxidation, and mitochondrial dysfunction, which were ameliorated by ferroptosis inhibitor ferrostatin-1. Transcriptomic analysis revealed substantial upregulation of heme oxygenase-1 (HO-1) following CdCl 2 exposure. Mechanistically, CdCl 2 triggered nuclear translocation of nuclear factor erythroid 2-related factor-2 (NRF2), subsequently activating HO-1 transcription. Over-activated HO-1 catalyzes the decomposition of heme and releases free iron, accompanied with the degradation of ferritin heavy chain 1 (FTH1) induced by CdCl 2 exposure, which leads to intracellular iron overload and excessive lipid peroxides production through Fenton reaction, resulting in ferroptosis ultimately. In vivo validation confirmed NRF2/HO-1-mediated ferroptosis in CdCl 2 -induced murine nephrotoxicity. Both pre-treatment with HO-1 competitive inhibitor Zinc protoporphyrin IX (ZnPP) and knockout of HO-1 gene remarkably alleviated PK-15 cells against ferroptosis induced by CdCl 2 treatment. Our findings demonstrate that Cd exposure initiates NRF2-mediated HO-1 overexpression, driving iron-dependent lipid peroxidation and subsequent ferroptosis. This mechanistic insight provides potential therapeutic targets for mitigating Cd-induced renal damage, advancing our understanding of heavy metal toxicity and its cellular consequences.
研究领域:
毒理学
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细胞生物学
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环境健康科学
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产品关联
DOI
PubMed
高影响因子
Current Nanoscience
·
2024
·Vol. 21
·期 4
·757-765
·
IF 1.4
Zirui Liu,Dan Li,Baofeng Zhao,Xifan Mei
BackgroundGouty arthritis, characterized by excruciating pain and discomfort, poses a significant burden on patients. While nanomedicines have shown promise in addressing this ailment, their complicated synthesis processes often involve potentially toxic procedures, contributing to adverse side effects in disease management.MethodsIn this study, we introduce a straightforward and elegant solution by utilizing easily prepared gold platinum (AuPt) nanoparticles for the treatment of gouty arthritis. The synthesis of these nanoparticles involves the use of gold and platinum precursors in conjunction with NaBH4, simplifying the manufacturing process. Experimental models of gout were established in both in vivo and in vitro settings through lipopolysaccharide and monosodium urate crystal induction.ResultsOur findings revealed that AuPt nanoparticles exhibited potent anti-inflammatory effects against gout. This effect was attributed to their ability to activate the Nrf2/HO-1 pathway, resulting in pain alleviation and the inhibition of inflammation, ultimately leading to the reduction of joint edema. With their uncomplicated synthesis and promising therapeutic potential, these simply prepared AuPt nanoparticles emerge as a compelling candidate for pharmaceutical intervention in the treatment of gouty arthritis.ConclusionThis approach not only holds the promise of delivering effective relief to patients but also minimizes the risk of unwanted side effects associated with complex nanomedicine synthesis processes.
研究领域:
药理学
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纳米医学
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炎症研究
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DOI
高影响因子
PHYTOMEDICINE
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2019
·
IF 4.18
Dan Chen,Ya-Xian Wu,Yu-bao Qiu,Bin-bin Wan,Gang Liu,Jun-liang Chen,Mu-dan Lu,Qing-feng Pang
Background Hypoxia is commonly existed in tumors and lead to cancer cell chemo/radio-resistance. It is well-recognized that tumor hypoxia is a major challenge for the treatment of various solid tumors . Hyperoside (quercetin-3-O-galactoside, Hy) possesses antioxidant effects and has been reported to protect against hypoxia/reoxygenation induced injury in cardiomyocytes . Therefore, Hy may be attractive compound applicable to hypoxia-related diseases . Purpose This study was designed to determine the role of Hy in hypoxia-induced proliferation of non-small cell lung cancer cells and the underlying mechanism. Study Design and Methods A549, a human non-small cell lung cancer (NSCLC) cell line, was used in the present study. 1% O 2 was used to mimic the in vivo hypoxic condition of NSCLC. The potential mechanisms of Hy on hypoxia-induced A549 survival and proliferation, as well as the involvement of AMPK/HO-1 pathway were studied via CCK-8 assay, EdU staining, flow cytometry, qRT-PCR and western blot . Results We showed that pretreatment with Hy suppressed hypoxia-induced A549 survival and proliferation in dose-dependent manner. In terms of mechanism, hypoxia-treated A549 showed the lower AMPK phosphorylation and the reduced HO-1 expression, which were reversed by Hy pretreatment. Both AMPK inhibitor (Compound C) and HO-1 activity inhibitor (Zinc protoporphyrin IX) abolished Hy-evoked A549 cell death under hypoxia stimuli. Of note, Ferrous iron contributed to Hy-induced A549 cell death under hypoxia, while Hy had no effect on lipid peroxidation under hypoxia. Conclusion Taken together, our results highlighted the beneficial role of Hy against hypoxia-induced A549 survival and proliferation through ferrous accumulation via AMPK/HO-1 axis.
研究领域:
肿瘤学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
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2025
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IF 4.7
Ji-Ping Wei,Bo Zhao,Zi-Jian Jiang,Peng-Yu Wang,Yan Xu,Ning Ding,Yuan-Yuan Hu,Wei Wang,Bo-Tao Jiang
Renal ischemia/reperfusion (I/R) injury is the most common cause of acute kidney injury (AKI). It can progress to chronic injury and subsequently to chronic kidney disease (CKD) via the renal fibrosis pathway. Luteolin is one of the most commonly occurring flavonoids and exhibits potential therapeutic activity against various pathophysiological processes. In this study, we investigated the protective role of luteolin in counteracting renal I/R injury and its potential mechanisms through systematic network pharmacology, molecular docking, and in vivo experimental studies. Using network pharmacology, we constructed and analyzed a luteolin-renal I/R injury target network. We assessed the relationship between luteolin and renal I/R injury targets using molecular docking analysis. Subsequently, we established a rat model of AKI to CKD transition using unilateral ischemia/reperfusion injury (UIRI), and detected changes in the expression of related proteins using biochemical indices. Network pharmacological analysis and molecular docking showed that luteolin affected renal I/R injury through multiple targets and pathways. As demonstrated by in vivo experiments, luteolin significantly attenuated renal I/R-induced oxidative injury by inhibiting renal lipid peroxidation in rats through the modulation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. Luteolin attenuated the levels of relevant inflammatory markers, significantly upregulated the synthesis of apoptosis-related proteins, and downregulated the expression of anti-apoptotic proteins. Our results suggest that luteolin effectively inhibited oxidative damage, inflammation, apoptosis, and fibrosis caused by renal I/R injury, thus exerting a nephroprotective effect. The antioxidant effects of luteolin may be related to the regulation of Nrf2/HO-1 signaling.
研究领域:
药理学
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分子生物学
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肾脏病学
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DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE
·
2014
·Vol. 50
·期 6
·2480-2490
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IF 2.305
Wei T.,Ye L.,Zhao C. Z.,Wang W. B.,Ma Q. Z.,Lv Q.,Liu J. M.
Filled tetragonal tungsten bronze (FTTB) oxides represent a huge family of materials which exhibit rich electric and magnetic functionalities deserving for comprehensive investigations. Recently, some members of this family have established their significance in efficient upconversion (UC) luminescence upon proper rare-earth species doping, while the signal intensity is yet weak. In this work, the UC luminescence of Ba
p
Ln 6− p
Ti 8− p
Nb 2+ p
O 30 codoped by Ho and Yb (BLTN p :Ho–Yb) with different p are studied. The bright UC green emission, red emission, and near-infrared (NIR) emissions, originating from the two-photon energy-transfer process associated with the 5 S 2 → 5 I 8 , 5 F 5 → 5 I 8 , and 5 S 2 → 5 I 7 transitions of Ho 3+ ions, were observed. The luminescence intensity demonstrates remarkable dependence on the A- and B-sites occupation, and the UC green, red, and NIR luminescence can be enhanced for 10, 25, and 10 times, respectively, upon a change of p from 3.5 to 5.0. This dependence is found to be tightly correlated with the crystal field environment, as characterized by the local lattice distortion. This work sheds light onto an alternative strategy to enhance the UC luminescence in this FTTB family.
研究领域:
材料科学
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光学
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DOI
高影响因子
Frontiers in Pharmacology
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2022
·
IF 5.988
Li Dafei,Zhao Haiyan,Xu Piao,Lin Qiongping,Zhao Tingting,Li Chubing,Cui Zhong-Kai,Tian Guangyong
Irreversible sensorineural hearing loss is one of the most common side effects after cisplatin treatment. Prevention and reversal of hearing loss caused by cisplatin are of great importance for cancer patients, especially children. Oxidative stress is an important cause of hearing loss resulted from cisplatin, unfortunately, there is no drug yet available that can completely prevent and reverse the ototoxicity from cisplatin. Polydatin (PD) possesses excellent antioxidant and anti-inflammatory effects, however, its role in the cisplatin-induced hearing loss has not been investigated. Herein, we have explored the preventive and therapeutic effects of PD on cisplatin-induced hearing loss and the possible underlying mechanisms. In the in vivo setting with guinea pigs, we have demonstrated that PD can reduce the threshold shift of auditory brainstem response (ABR) caused by cisplatin, promote the nuclear translocation of Nuclear factor erythroid-2 related factor 2 (Nrf2), increase the expression of Nrf2 and heme oxygenase-1 (HO-1), and thus reduce the loss of outer hair cells (OHCs). PD can ameliorate cisplatin-induced hearing loss through activating the Nrf2/HO-1 signaling pathway. This study provides a potential strategy for preventing and improving hearing loss resulted from cisplatin treatment in clinics.
研究领域:
药理学
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耳鼻喉科学
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肿瘤学
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DOI
PubMed
高影响因子
NEUROCHEMISTRY INTERNATIONAL
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2025
·
IF 4
Yinpei Huang,Hailun Xie,Lian Liu,Heng Zhao,Bing Li,Feng Zhang
Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (IH), which induces oxidative stress and neuronal apoptosis, ultimately leading to progressive cognitive impairment. This study investigated the neuroprotective potential of a reactive oxygen species (ROS)-responsive nanotherapeutic, namely TPCD nanoparticles (TPCD NP), synthesized through the conjugation of Tempol and phenylboronic acid pinacol ester to β-cyclodextrin, in both in vivo and in vitro models. In rats, intravenous administration of TPCD NP improved memory performance as assessed by the Morris water maze test, and preserved hippocampal neuronal morphology. TPCD NP significantly reduced intracellular ROS content and malondialdehyde (MDA) levels while restoring antioxidant capacity, including superoxide dismutase (SOD) and glutathione (GSH). Apoptosis was attenuated, as evidenced by the downregulation of Bax and cleaved caspase-3, and the upregulation of Bcl-2 expression. Mechanistically, TPCD NP enhanced the nuclear translocation of nuclear factor erythroid 2–related factor 2 (NRF2), suppressed Kelch-like ECH-associated protein 1 (KEAP1), and increased heme oxygenase-1 (HO-1) expression. The protective effects were abolished by ML385, a selective NRF2 inhibitor, confirming the essential role of NRF2 activation in mediating the antioxidant and anti-apoptotic effects of TPCD NP. In conclusion, TPCD NP attenuates oxidative stress and apoptosis induced by IH in the hippocampus by activating the NRF2/KEAP1/HO-1 pathway. These findings highlight TPCD NP as a promising therapeutic strategy for OSA-associated neurodegeneration.
研究领域:
医学
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神经科学
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药理学
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产品关联
DOI
PubMed
高影响因子
CLINICAL AND EXPERIMENTAL HYPERTENSION
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2025
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IF 3.5
Hao Wang,Ke Zhou,Xiaoling Chen,Yao Tong,Qiuyan Jiang,Qiang She,Jun Xiao
Myocardial infarction (MI) is a leading cause of morbidity and mortality globally, primarily due to oxidative stress-induced cardiomyocyte apoptosis and adverse cardiac remodeling. OL-FS13, a neuroprotective peptide derived from Odorrana livida, has previously shown anti-apoptotic effects in cerebral ischemia models. However, its role in myocardial protection remains unclear. In this study, we investigated the cardioprotective effects of OL-FS13 in both in vitro and in vivo models of MI. Hydrogen peroxide (H₂O₂) was used to induce oxidative stress in primary neonatal rat cardiomyocytes, while permanent ligation of the left anterior descending (LAD) coronary artery was employed to establish a murine MI model. OL-FS13 treatment significantly attenuated cardiomyocyte apoptosis, reduced ROS accumulation, improved left ventricular function, and decreased infarct size. Mechanistically, OL-FS13 activated the Nrf2/HO-1 signaling pathway, restoring antioxidant protein levels and suppressing oxidative stress-induced apoptosis. Pharmacological inhibition of Nrf2 with ML385 abrogated the antioxidant and anti-apoptotic effects of OL-FS13 both in vitro and in vivo, confirming the central role of this pathway. These findings demonstrate that OL-FS13 exerts potent cardioprotective effects via Nrf2/HO-1 pathway activation and ROS suppression, suggesting its potential as a novel therapeutic agent for the treatment of myocardial infarction.
研究领域:
心血管病学
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分子药理学
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氧化应激生物学
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心肌缺血再灌注损伤
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信号转导
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产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2025
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IF 3.5
Ziyang Huang,Ruijia Xu,Zhongjun Wan,Chao Liu,Jinquan Li,Jun He,Li Li
Cadmium (Cd) is a prevalent heavy metal pollutant known to cause lung damage. However, the mechanisms underlying Cd-induced lung injury and the associated therapeutic strategies remain unclear. By establishing Cd-induced lung damage models both in vivo and in vitro , we observed that Cd inhibited the Nrf2/HO-1 signaling pathway, disrupted the redox balance in lung tissue, accelerated endoplasmic reticulum (ER) stress, and promoted ferroptosis, ultimately leading to lung injury. Melatonin (Mel), a potent reactive oxygen species (ROS) inhibitor with high antioxidative efficacy, mitigated the increasing in ROS and the decreasing in superoxide dismutase levels induced by Cd, as well as the upregulation of PERK-eIF2α-ATF4 signaling associated with ER stress, through the activation of the Nrf2/HO-1 signaling pathway. Furthermore, Mel administration not only prevented Cd-induced iron overload but also reduced lipid peroxidation levels, thereby improving mitochondrial morphological alterations. Collectively, our results demonstrated that Mel treatment alleviated Cd-induced lung injury by inhibiting oxidative stress, which in turn ameliorated ER stress and ferroptosis through the activation of the Nrf2/HO-1 pathway.
研究领域:
毒理学
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分子生物学
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呼吸系统医学
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产品关联
DOI
PubMed
高影响因子
NEUROCHEMICAL RESEARCH
·
2022
·Vol. 48
·期 2
·579-590
·
IF 4.414
Shen Mengya,Zheng Yuantie,Li Ge,Chen Yinqi,Huang Lili,Wu Jianzhang,Hong Chenglv
Abstract Antioxidants represent a potential therapy for cerebral ischemia–reperfusion injury (CIRI). Compounds which exhibit both direct and indirect antioxidative activity may potentially exert improved effects. Hence, we aimed to assess whether the dual antioxidant DH-217, a derivative of DHAP clinically used to treat coronary heart disease, can reduce oxidative stress damage and elucidate the underlying mechanism. Hydrogen peroxide (H 2 O 2 )-induced and Middle Cerebral Artery Occlusion (MCAO)-induced damages were used to imitate oxidative stress. The antioxidation of DH-217 was determined by MTT, ROS, colony and DPPH assay. Besides, immunofluorescence, Real-Time PCR Analyses, western blotting and si-RNA/Plasmid-induced protein expression were used for mechanism validation. DPPH scavenging assay evidenced DH-217 was a well free radical scavenger. Cell survival assay also showed that DH-217 had a significant cytoprotection through direct and indirect clearance mechanisms. Further, it clearly inhibited oxidative stress-induced IkappaB kinase beta (IKKβ) phosphorylation and increased heme oxygenase-1 (HO-1) expression. Significantly, these antioxidant beneficial effects were reversed by HO-1 inhibitor, si-nuclear erythroid 2-related factor 2 (Nrf2) and IKKβ plasmid. Meanwhile, DH-217 had a good neuroprotective effect on CIRI rats. The dual antioxidant DH-217 has potential reference value for drug development of CIRI. Furthermore, inhibition of IKKβ phosphorylation and activation of Nrf2/HO-1 could be a promising antioxidant pathway. Graphical Abstract Dual antioxidant DH-217 not only has the ability of directly scavenging ROS, but also can clear it by targeting IKKβ/Nrf2/HO-1 signal axis. Inhibition of IKKβ phosphorylation and activation of Nrf2/HO-1 may be a promising antioxidant pathway for CIRI.
研究领域:
药理学
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神经科学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Pharmaceuticals
·
2022
·Vol. 15
·期 12
·1548
·
IF 5.215
Fei Yang,Cuizhen Shen
On the basis of the mice pressure ulcers (PU) model, the protective effect and potential mechanism of sodium Danshensu (SDSS) cream against PU were investigated. The mice were randomly divided into three groups: the negative control group (cream without 0.5 g SDSS), the SDSS group (cream containing 0.5 g SDSS), and the positive group (0.5 g Hirudoid®). After 7 and 14 days of ointment application, the wound-healing rate of the SDSS and positive groups was significantly higher than that of the control group (p< 0.05). The results of hematoxylin–eosin staining also indicated that SDSS has the potential to promote the healing of PU. In addition, the serum IL-6, IL-1β, TNF-α, and MDA levels decreased significantly (p< 0.01) after 14 days of SDSS treatment, while the SOD, CAT, and GSH-Px activities increased significantly (p< 0.01). In addition, SDSS cream was able to significantly increase the expression of Nrf2, HO-1, GCLM, NQO1, NF-κB p65, NF-κB p50, IKKα, and IKKβ while decreasing the expression of Keap1 and IκBαin the Nrf2/HO-1 and NF-κB pathways. Our research will provide a foundation for the future clinical prevention and treatment of PU with SDSS cream.Keywords:pressure ulcers;sodium Danshensu cream;ischemia/reperfusion injury;Nrf2/HO-1 pathway;NF-κB pathway
研究领域:
药理学
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伤口愈合
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炎症
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氧化应激
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产品关联
DOI
PubMed
高影响因子
Frontiers in Neuroscience
·
2019
·
IF 3.648
Chen Xiao,Xi Zhiyu,Liang Huaibin,Sun Yuhao,Zhong Zhihong,Wang Baofeng,Bian Liuguan,Sun Qingfang
Secondary injuries mediated by oxidative stress lead to deterioration of neurological functions after intracerebral hemorrhage (ICH). Cortical astrocytes are among the most important cells in the central nervous system (CNS), and play key roles in maintaining redox homeostasis by providing oxidative stress defense. Hemin is a product of hemoglobin degradation, which has strong toxicity and can induce reactive oxygen species (ROS). Melatonin (Mel) and its metabolites are well tolerated without toxicity, prevent tissue damage as well as effectively assist in scavenging free radicals. We evaluated the hemin neurotoxicity to astrocytes and the resistance of Mel-treated astrocytes to hemin neurotoxicity. And we found Mel induced PKCα phosphorylation (p-PKC), nuclear translocation of Nrf2 in astrocytes, and upregulation of HO-1, which contributed to the reduction of ROS accumulation and cell apoptosis. Nrf2 and HO1 protein expression upregulated by Mel were decreased after administration of PKC inhibitor, Ro 31-8220 (Ro 31). Luzindole (Luz), a melatonin receptor inhibitor, suppressed p-PKCα, HO-1, and Nrf2 expression upregulated by Mel and increased cell apoptosis rate. The upregulation of HO-1 induced by Mel was depressed by knocking down Nrf2 expression by siRNA, which also decreased the resistance of astrocytes to toxicity of hemin. Mel activates astrocytes through PKCα/Nrf2/HO-1 signaling pathway to acquire resistance to toxicity of hemin and resist from oxidative stress and apoptosis. The positive effect of Mel on PKCα/Nrf2/HO-1 signaling pathway may become a new target for neuroprotection after intracerebral hemorrhage.
研究领域:
神经科学
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药理学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
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