ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
·
2024
·
IF 3.8
Haiyan Zhu,Yijing Yang,Yenan Duan,Xin Zheng,Zixiong Lin,Jie Zhou
Sodium aescinate (SA), an active compound found in horse chestnut seeds, is widely used in clinical practice. Recently, the incidence of SA-induced adverse events , particularly renal impairment, has increased. Our previous work demonstrated that SA causes severe nephrotoxicity via nephrocyte ferroptosis ; however, the underlying mechanism remains to be fully elucidated. In the current study, we investigated additional molecular pathways involved in SA-induced nephrotoxicity. Our results showed that SA inhibited cell viability , disrupted cellular membrane integrity, and enhanced reactive oxygen species (ROS), ferrous iron (Fe 2+ ), and malondialdehyde (MDA) levels, as well as lipid peroxidation in rat proximal renal tubular epithelial cell line (NRK-52E) cells. SA also depleted coenzyme Q10 (CoQ10, ubiquinone) and nicotinamide adenine dinucleotide (NADH) and reduced ferroptosis suppressor protein 1 (FSP1) and polyprenyltransferase (coenzyme Q2, COQ2) activity, triggering lipid peroxidation and ROS accumulation in mouse kidneys and NRK-52E cells. The overexpression of COQ2, FSP1, or CoQ10 (ubiquinone) supplementation effectively attenuated SA-induced ferroptosis, whereas iFSP1 or 4-formylbenzoic acid (4-CBA) pretreatment exacerbated SA-induced nephrotoxicity. Additionally, SA decreased nuclear factor-erythroid-2-related factor 2 (Nrf2) levels and inhibited Nrf2 binding to the −1170/-1180 bp ARE site in FSP1 promoter, resulting in FSP1 suppression. Overexpression of Nrf2 or its agonist dimethyl fumarate (DMF) promoted FSP1 expression, thereby improving cellular antioxidant capacity and alleviating SA-induced ferroptosis. These results suggest that SA-triggers renal injury through oxidative stress and ferroptosis, driven by the suppression of the Nrf2/FSP1/CoQ10 axis.
研究领域:
药理学
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毒理学
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细胞生物学
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分子生物学
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肾脏生理学
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产品关联
DOI
PubMed
高影响因子
Cell Chemical Biology
·
2026
·
IF 9
Tae Ha Kim,Chi Thi Ngoc Nguyen,Dahee Jang,Sae Bom Lee,Yun Jae Cha,Seon Min Kim,Yun Ji Lim,Tae Hwan Choi,Taeryeong Kim,Jae-Young Lee,Eun-Woo Lee,Sung Eun Kim,Tong-Shin Chang,You Jeong Lee,Maria Fedorova,Derek A. Pratt,Marcus Conrad,Sung Won Kwon,Yun Pyo Kang
Coenzyme Q (CoQ) is an essential electron carrier and lipophilic antioxidant whose biological functions depend on its redox state. However, accurate measurement of reduced and oxidized CoQ is hindered by rapid ex vivo oxidation during sample preparation and analysis. Here, we develop a dual-isotope-based oxidation-correction LC-MS/MS platform that enables accurate quantification of CoQ redox status across diverse biological matrices. Coupled with rapid subcellular fractionation, this approach resolves cytosolic and mitochondrial CoQ pools and reveals that the CoQ 10 H 2 /CoQ 10 ratio is substantially higher in the cytosol than in mitochondria. During ferroptosis, compartment-specific remodeling of CoQ redox status is observed, consistent with distinct roles for CoQ in plasma membrane and mitochondrial biology. The platform also enables robust analysis of plasma CoQ redox status in mouse and human samples. These advances provide a broadly applicable approach for studying redox biology, ferroptosis, mitochondrial metabolism, and biomarker discovery.
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2025
·
IF 16
Lei Shu,Peili Luo,Chuanyu Ren,Ziwei Lai,Xuejuan Zhang,Chuanbin Wu,Xin Pan,Zhengwei Huang
The application of ferroptosis inducer FIN56 to decrease antioxidant levels in lung adenocarcinoma (LUAD) is a promising tumor eradication technique. However, several obstacles reduce the efficacy of ferroptosis therapy including insufficient oxidative stress from monotherapy and restricted drug retention in tumor tissues. To address these challenges, we developed an inhalable hybrid liposome in which FIN56 and piperlongumine (PPL) are coloaded into silk fibroin nanoparticles to overcome the limitation of the poor therapeutic effect of single-drug ferroptosis. Subsequently, lipids containing hyaluronic acid were added to the hybrid liposome to enable it to specifically target the overexpressed CD44 receptors on the surface of LUAD cells and solve the problem of insufficient active targeting of silk fibroin nanoparticles. Compared to conventional intravenous formulations, the as-synthesized formulation FP@SLCDH increased pulmonary accumulation by 13.6-fold and lipid peroxidation products by 2.14-fold. FIN56 prompts tumor-specific ferroptosis by inhibiting glutathione peroxidase 4 (GPX4) and glutathione (GSH), whereas PPL further augments this effect by increasing intracellular reactive oxygen species levels and facilitating ferritin degradation to release Fe ions from ferritin. The role of autophagy in promoting ferroptosis and therapeutic efficacy was validated in an orthotopic LUAD tumor model. The real-time tracking of targeted retention of FP@SLCDH in LUAD cells is also possible using an aggregation-induced emission probe, which is facilitated as a “double-lock logic gate fluorescence probe”. This probe emits fluorescence signals only after entering cancer cells and arriving at the mitochondria. To summarize, our proposed hybrid liposomes represent a significantly enhanced pulmonary strategy for LUAD therapy.
研究领域:
药学
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纳米技术
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肿瘤学
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生物化学
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药物递送系统
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分子生物学
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产品关联
DOI
PubMed
高影响因子
NANOTECHNOLOGY
·
2023
·Vol. 34
·期 39
·395503
·
IF 3.5
Zhiwen Li,Zhilin Zhou,Jianghua Wang,Tingxian Tao,Yingqiang Fu
Carbon quantum dots (CQDs) have been extensively researched as fluorescent probes, but there are few reports on fluorescence-enhanced probes. Herein, nitrogen and sulfur co-doped CQDs (N, S-CQDs) with blue aggregation-induced emission enhancement (AIEE) fluorescence were synthesized by a one-step hydrothermal reaction. N, S-CQDs can rely on the presence of –OH, C=O, –NH2, and ether bonds on their surfaces and the formation of hydrogen bonds by ciprofloxacin (CIP) containing Ar-F and –COOH functional groups to achieve effective charge transfer. In addition, CIP forces N, S-CQDs to aggregate to form cross-linked structures, which effectively limits the vibration and rotation of N, S-CQDs, leading to enhanced fluorescence of N, S-CQDs. Based on the above intermolecular charge transfer and AIEE between N, S-CQDs and CIP, an efficient and sensitive nano fluorescent probe for the detection of CIP in real water samples was developed, which can achieve sensitive detection of 3.33 × 10−8–1.13 × 10−6 M CIP.
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产品关联
DOI
PubMed
高影响因子
VETERINARY PARASITOLOGY
·
2025
·
IF 2.2
Xiao Tu,Jiaxin Hu,Jinghao Peng,Qihan Chen,Yangle Zhao,Zemao Gu
Monogenean parasites are harmful pathogens in aquaculture systems. Current treatment strategies for monogenean infections are unsatisfactory, making the discovery of new drugs urgent. Thymoquinone (TQ), a natural monoterpene isolated from Nigella sativa L., has demonstrated its potential as lead structure against the monogenean parasites. In the present study, the anthelmintic activity of 26 selected TQ analogues was investigated against the monogenean parasite Gyrodactylus kobayashii in the goldfish ( Carassius auratus ). The results indicated that 18 TQ analogues displayed the EC 50 value below 1.0 mg/L, 14 of them showed more potent anthelmintic activity than TQ (EC 50 =0.303 mg/L). Particularly, compounds 9 and 23 exhibited the best efficacies with the EC 50 values of 0.058 and 0.034 mg/L, outperforming the standard drug praziquantel as well. Structure-activity relationship analysis revealed that large electron-donating substituents at the 2-position of the quinone ring contribute to enhanced in vivo anthelmintic activity. Additionally, four analogues ( 9 , 12 , 23 and 25 ) displayed low fish toxicity, with the therapeutic index (TI, LC 50 /EC 50 ) above 9.23, and were selected for further in silico drug‑likeness assessment. The results demonstrated an excellent drug-likeness profile and an adherence to major pharmaceutical companies’ filters for compounds 9 and 23 . Besides, TQ analogue 9 was chosen for an in vivo study in large-scale trial based on its potency, low fish toxicity, and excellent drug-likeness profiles. Treatment of G. kobayashii infected goldfish for 24 h at 0.1 and 0.2 mg/L was effective, reducing the infection prevalence from 100 % to 0 % post-treatment. The experimental fish exhibited normal behavior, despite minor modifications were displayed in the gills and liver according to histopathological results. Collectively, this study suggested that TQ analogues are excellent scaffolds in the discovery of novel anthelmintic agents against monogenean infections.
研究领域:
水产养殖学
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药理学
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寄生虫学
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产品关联
DOI
PubMed
高影响因子
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