TOXICOLOGY AND APPLIED PHARMACOLOGY
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2024
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IF 3.3
Li Tao,Yu-Feng Xue,Fei-Fei Sun,Xue He,Hong-Qian Wang,Cheng-Cheng Tong,Cheng Zhang,De-Xiang Xu,Xi Chen
Ferroptosis has been shown to be involved in carbon tetrachloride (CCl 4 )-induced acute liver injury (ALI). The mitochondrion-targeted antioxidant MitoQ can eliminate the production of mitochondrial reactive oxygen species (mtROS). This study investigated the role of MitoQ in CCl 4 -induced hepatocytic ferroptosis and ALI. MDA and 4HNE were elevated in CCl 4 -induced mice. In vitro, CCl 4 exposure elevated the levels of oxidized lipids in HepG2 cells. Alterations in the mitochondrial ultrastructure of hepatocytes were observed in the livers of CCl 4 -evoked mice. Ferrostatin-1 (Fer-1) attenuated CCl 4 -induced hepatic lipid peroxidation, mitochondrial ultrastructure alterations and ALI. Mechanistically, acyl-CoA synthetase long-chain family member 4 (ACSL4) was upregulated in CCl 4 -exposed human hepatocytes and mouse livers. The ACSL4 inhibitor rosiglitazone alleviated CCl 4 -induced hepatic lipid peroxidation and ALI. ACSL4 knockdown inhibited oxidized lipids in CCl 4 -exposed human hepatocytes. Moreover, CCl 4 exposure decreased the mitochondrial membrane potential and OXPHOS subunit levels and increased the mtROS level in HepG2 cells. Correspondingly, MitoQ pretreatment inhibited the upregulation of ACSL4 in CCl 4 -evoked mouse livers and HepG2 cells. MitoQ attenuated lipid peroxidation in vivo and in vitro after CCl 4 exposure. Finally, MitoQ pretreatment alleviated CCl 4 -induced hepatocytic ferroptosis and ALI. These findings suggest that MitoQ protects against hepatocyte ferroptosis in CCl 4 -induced ALI via the mtROS-ACSL4 pathway.
研究领域:
医学
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生物化学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
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2024
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IF 6.1
Ying Tan,Yali Nie,Lei ZhengWen,Zhi Zheng
In cardiac tissue engineering, myocardial surface patches and hydrogel intramyocardial injections represent the two primary hydrogel-based strategies for myocardial infarction (MI) treatment. However, the comparative effectiveness of these two treatments remains uncertain. Therefore, this study aimed to compare the effects of the two treatment modalities by designing a simple and reproducible hydrogel cross-linked with γ-PGA and 4-arm-PEG-SG. To improve mitochondrial damage in cardiomyocytes (CMs) during early MI, we incorporated the mitochondria-targeting antioxidant MitoQ into the hydrogel network. The hydrogel exhibited excellent biodegradability, biocompatibility, adhesion, and injectability in vitro. The hydrogel was utilized for rat MI treatment through both patch adhesion and intramyocardial injections. In vivo results demonstrated that the slow release of MitoQ peptide from the hydrogel hindered ROS production in CM, alleviated mitochondrial damage, and enhanced CM activity within 7 days, effectively inhibiting MI progression. Both hydrogel intramyocardial injections and patches exhibited positive therapeutic effects, with intramyocardial injections demonstrating superior efficacy in terms of cardiac function and structure in equivalent treatment cycles. In conclusion, we developed a MitoQ/hydrogel system that is easily prepared and can serve as both a myocardial patch and an intramyocardial injection for MI treatment, showing significant potential for clinical applications.
研究领域:
心脏组织工程
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生物医学工程
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心脏病学
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药学
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产品关联
DOI
PubMed
高影响因子
Oxidative Medicine and Cellular Longevity
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2021
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IF 6.543
Bao-Liang Li,Xizhe Liu,Manman Gao,Fu Zhang,Xu Chen,Zhongyuan He,Jianmin Wang,Wei Tian,Dafu Chen,Zhiyu Zhou,Shaoyu Liu
Increasing evidence has indicated that mitochondrial reactive oxygen species (ROS) play critical roles in mechanical stress-induced lumbar degenerative disc disease (DDD). However, the detailed underlying pathological mechanism needs further investigation. In this study, we utilized a one-strike loading disc degeneration organ culture model to explore the responses of intervertebral discs (IVDs) to mechanical stress. IVDs were subjected to a strain of 40% of the disc height for one second and then cultured under physiological loading. Mitoquinone mesylate (MitoQ) or other inhibitors were injected into the IVDs. IVDs subjected to only physiological loading culture were used as controls. Mitochondrial membrane potential was significantly depressed immediately after mechanical stress (). The percentage of ROS-positive cells significantly increased in the first 12 hours after mechanical stress and then declined to a low level by 48 hours. Pretreatment with MitoQ or rotenone significantly decreased the proportion of ROS-positive cells (). Nucleus pulposus (NP) cell viability was sharply reduced at 12 hours after mechanical stress and reached a stable status by 48 hours. While the levels of necroptosis- and apoptosis-related markers were significantly increased at 12 hours after mechanical stress, no significant changes were observed at day 7. Pretreatment with MitoQ increased NP cell viability and alleviated the marker changes by 12 hours after mechanical stress. Elevated mitochondrial ROS levels were also related to extracellular matrix (ECM) degeneration signs, including catabolic marker upregulation, anabolic marker downregulation, increased glycosaminoglycan (GAG) loss, IVD dynamic compressive stiffness reduction, and morphological degradation changes at the early time points after mechanical stress. Pretreatment with MitoQ alleviated some of these degenerative changes by 12 hours after mechanical stress. These changes were eliminated by day 7. Taken together, our findings demonstrate that mitochondrial ROS act as important regulators of programmed NP cell death and ECM degeneration in IVDs at early time points after mechanical stress.
研究领域:
骨科学
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细胞生物学
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生物力学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2025
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IF 8.2
Wenjia Xie,Yuxuan Wang,Jicenyuan Wu,Xu Wang,Jiaxin Wu,Bin Cheng,Hao Feng,Xinxu Huang,Xinting Cheng,Junyu Chen,Qianbing Wan,Jian Wang,Xibo Pei
Diabetic periodontitis is characterized by persistent and aggravated inflammation, largely driven by a reactive oxygen species (ROS) vicious loop in M1 macrophages driven by mitochondrial dysfunction. To disrupt this pathogenic cascade, we developed hierarchically targeted polymeric nanoparticles (MPPT NPs) by conjugating the tuftsin peptide for selective uptake by M1 macrophages and loading mitoquinone mesylate (MitoQ) to restore mitochondrial function after mitochondrial localization. For local retention and responsive drug release, MPPT NPs were incorporated into a ROS-responsive hydrogel (MTP hydrogel) constructed by cross-linking poly(vinyl alcohol) (PVA) with a ROS-cleavable linker (N1-(4-boronobenzyl)-N3-(4-boronophenyl)-N1,N1,N3,N3-tetramethylpropane-1,3-diaminium (TSPBA)). This constructed platform not only enabled the on-demand release of MPPT NPs but also provided additional ROS-scavenging ability. In vitro studies demonstrated that MTTP NPs effectively repaired oxidatively damaged mitochondria and suppressed NLRP3 inflammasome priming and activation. MTP hydrogel platform reduced pro-inflammatory cytokine release and rescued inflammation-induced osteogenic impairment. In a diabetic periodontitis rat model, local administration of the MTP hydrogel significantly attenuated periodontal tissue destruction and promoted alveolar bone regeneration, achieving BV/TV 1.5 times that of previous reports. Collectively, this hierarchically targeted and ROS-responsive platform disrupts the ROS vicious loop in M1 macrophages by repairing damaged mitochondria, offering a promising therapeutic strategy for the management of diabetic periodontitis.
研究领域:
纳米医学
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牙科
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免疫学
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活性氧信号通路
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生物材料
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炎症性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）