Toxicologie Analytique et Clinique
·
2025
·
IF 1.7
Jiajun Sun,Xiaolong Zhang,Mengchao Wang,Xiaoyu Zhou,Yuxuan Chen,Jinlei liu,Yinyin Dai,Kundi Zhao,Yaqin Sun,Jie Gu,Huimin Zhang,Shengnan Zhang,Amin Wurita,Koutaro Hasegawa
Purpose Fluoxetine is a clinically used antidepressant, due to its slimming effect, unscrupulous elements will add it to slimming products. The aim of this study was to establish an optimized derivatization method for fluoxetine and norfluoxetine to be analized by a gas chromatography-tandem mass spectrometry (GC-MS/MS) and apply it to real case. Methods Hair samples were washed and cut into approximately 2 mm, and 50 mg was added to the internal standard and hydrolyzed with 1% sodium hydroxide solution. Add 3 mL ethyl acetate, vortex and centrifuge; urine samples were taken as 1 mL and then added to the internal standard and 3 mL ethyl acetate, then submitted to vortex and centrifugation. The supernatant was evaporated to dryness under a nitrogen gas stream and then derivatized by adding 25 μL ethyl acetate and 25 μL HFBA at 70 °C for 45 minutes and later analyzed by GC-MS/MS. The derivatisation procedure for the remaining derivatisation reagents TFAA, FPPA, MSTFA and 99% BSTFA + 1% TMCS was the same as above. Result Fluoxetine and norfluoxetine were analyzed by GC-MS/MS and the validation data were satisfactory. The derivatization reagent HFBA was the most effective for the modification of fluoxetine and norfluoxetine. The concentrations of fluoxetine in hair and urine extracts were 40.9 ng/mg and 10.8 ng/mL, respectively; the concentrations of norfluoxetine were 4.94 ng/mg and 7.57 ng/mL, respectively. Conclusion A method for the determination of fluoxetine and norfluoxetine in human hair and urine by GC-MS/MS was developed and applied to real cases. Furthermore, the chemical modification effects of five derivatization reagents on fluoxetine and norfluoxetine were compared, and the best effect was obtained by HFBA at 70 °C for 45 min.
研究领域:
分析化学
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毒理学
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临床医学
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产品关联
DOI
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2025
·
IF 6.8
Jia-Qian Wang,Xiao-Meng Liu,Zi-Shuo Zhu,Zhe Li,Cheng-Zhi Xie,Xin Qiao,Yu-Kuan Feng,Jing-Yuan Xu
Triple-negative breast cancer (TNBC) poses formidable challenges in the clinic owing to its particularly malignant and aggressive properties. Overexpression of eukaryotic elongation factor-2 kinase (eEF2K) is highly correlated with the poor prognosis of TNBC, representing a promising therapeutic target. Herein, Fluoxetine as eEF2K-inhibitor and chemosensitizer was conjugated with cisplatin/oxaliplatin to present two-in-one prodrugs 8–19. Multievaluation indicated that monosubstituted 8 and disubstituted 12 exhibited 407- and 174-fold higher cytotoxicity than cisplatin against MDA-MB-231 cells by elevating DNA damage-induced apoptosis and eEF2K-triggered autophagy. Moreover, 8 and 12 significantly overcame chemoresistance in A549cisR cells, evidenced by downregulating resistance-related key proteins P-gp, GST-π, ATM, and RAD51. Syngeneic and xenograft mouse models demonstrated that 8 and 12 could effectively inhibit tumor growth and metastasis, and reduce toxicity compared to cisplatin in vivo. Additionally, 8 and 12 stimulated immunomodulation including T-cell proliferation and Th1 cytokine production. All results hold the promise of 8 and 12 as multifunctional chemotherapeutic agents.
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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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2019
·Vol. 20
·期 17
·4282
·
IF 4.183
Yunfeng Zhou,Xue Tao,Zhi Wang,Li Feng,Lisha Wang,Xinmin Liu,Ruile Pan,Yonghong Liao,Qi Chang
An olfactory bulbectomy (OBX) rodent is a widely-used model for depression (especially for agitated depression). The present study aims to investigate the hippocampus metabolic profile and autophagy-related pathways in OBX rats and to explore the modulatory roles of fluoxetine. OBX rats were given a 30-day fluoxetine treatment after post-surgery rehabilitation, and then behavioral changes were evaluated. Subsequently, the hippocampus was harvested for metabonomics analysis and Western blot detection. As a result, OBX rats exhibited a significantly increased hyperemotionality score and declined spatial memory ability. Fluoxetine reduced the hyperemotional response, but failed to restore the memory deficit in OBX rats. Sixteen metabolites were identified as potential biomarkers for the OBX model including six that were rectified by fluoxetine. Disturbed pathways were involved in amino acid metabolism, fatty acid metabolism, purine metabolism, and energy metabolism. In addition, autophagy was markedly inhibited in the hippocampus of OBX rats. Fluoxetine could promote autophagy by up-regulating the expression of LC3 II, beclin1, and p-AMPK/AMPK, and down-regulating the levels of p62, p-Akt/Akt, p-mTOR/mTOR, and p-ULK1/ULK1. Our findings indicated that OBX caused marked abnormalities in hippocampus metabolites and autophagy, and fluoxetine could partly redress the metabolic disturbance and enhance autophagy to reverse the depressive-like behavior, but not the memory deficits in OBX rats.Keywords:olfactory bulbectomy;depression;hippocampus;metabonomics;autophagy
研究领域:
神经科学
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药理学
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行为科学
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产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2018
·Vol. 8
·期 1
·1-10
·
IF 4.122
Bi Ran,Zeng Xiangfeng,Mu Lei,Hou Liping,Liu Wenhua,Li Ping,Chen Hongxing,Li Dan,Bouchez Agnes,Tang Jiaxi,Xie Lingtian
Increasing release of pharmaceuticals and personal care products (PPCPs) into aquatic ecosystems is a growing environmental concern. Triclosan and fluoxetine are two widely used PPCPs and frequently detected in aquatic ecosystems. In this study, the sensitivities of 7 algal species from 4 genera to triclosan, fluoxetine and their mixture were evaluated. The results showed that the inhibitory effect on algal growth (EC 50 -96h) of triclosan varied with 50 times differences among the 7 algal species. Chlorella ellipsoidea was the least susceptible species and Dunaliella parva was the most sensitive species to triclosan. The inhibitory effect of fluoxetine was less variable than triclosan. Slightly higher toxicity of fluoxetine than triclosan was shown in the 7 tested algal species. No consistent pattern of the effects from mixture of triclosan and fluoxetine was observed among the 7 algal species and among the 4 genera. Additive effects of the mixture occured in 4 species and antagonistic effects in the other 3 species but no synergistic effect was detected. The algal species might show some sign of phylogenetic response to triclosan, as evidenced by the wide range of differences in their sensitivity at the genus level. This study provides important data which could be beneficial for biomonitoring programs on the ecological risk (algal species diversity) of these two chemicals.
研究领域:
环境科学
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毒理学
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DOI
PubMed
高影响因子
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
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2023
·Vol. 79
·期 1
·
IF 5.1
Zhou Can,Zhou Yiming,Liang Yu,Chen Lijuan,Liu Li,Wei Fang,Li Guolin
Although several antidepressants have been identified as potential geroprotectors, the effect and mechanism of fluoxetine, a representative selective serotonin reuptake inhibitor, on longevity have not been fully elucidated. Here, we found that fluoxetine promoted longevity in Caenorhabditis elegans with a concomitant extension of a healthy life span as indicated by increasing mobility, reducing fertility and lipofuscin accumulation, and enhanced resistance to different abiotic stresses. Fluoxetine increased the level of reactive oxygen species (ROS), and antioxidant N-acetylcysteine abolished ROS elevation and the pro-longevity effect of fluoxetine. Additionally, fluoxetine extended life span through the daf-2-sod-3 pathway in daf-16-dependent and -independent manners, and fluoxetine-induced life-span extension was abolished in C. elegans sod-3, daf-2, and daf-16 mutants. In conclusion, these findings suggest that fluoxetine can promote health and longevity in C. elegans via the interaction of ROS and insulin signaling.
研究领域:
生物学
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医学
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神经科学
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衰老研究
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2020
·
IF 10.652
Rui Bai,Weifu Yan,Yong Xiao,Siqi Wang,Xiaochun Tian,Junpeng Li,Xiaofeng Xiao,Xiaoquan Lu,Feng Zhao
By modifying copper ferrite on the surface of molybdenum disulfide (MoS 2 /CuFe 2 O 4 ), an excellent catalyst that can be used for interaction with peroxymonosulfate was successfully synthesized. Owing to the large number of active sites (unsaturated sulfur) on the surface of the composite material, the electron transfer and decomposition rate of the oxidant in the reaction system were significantly enhanced. The removal ability was the strongest when the molar ratio of MoS 2 /CuFe 2 O 4 was 1.5. The removal efficiency of fluoxetine reached 97.7% within 20 min, which was higher than those obtained by pure MoS 2 (38.6%) and CuFe 2 O 4 (22.1%). The free radical test and electron paramagnetic resonance analysis indicated that sulfate radicals and hydroxyl radicals were the dominant reactive oxygen species in the reaction system. In addition, in situ Raman spectroscopy revealed that peroxymonosulfate was rapidly decomposed in the composite material system. Meanwhile, the degradation products of fluoxetine were explored by high-performance liquid chromatography-tandem mass spectrometry, and a transformation pathway based on nine intermediates was proposed, mainly involving the breaking of the carbon-oxygen bond around oxygen atom, hydroxylation, and ring-opening reactions of fluoxetine and its intermediates.
研究领域:
环境科学
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材料科学
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产品关联
DOI
高影响因子
FUNDAMENTAL & CLINICAL PHARMACOLOGY
·
2025
·Vol. 39
·期 1
·e13048
·
IF 2.5
Langtao He,Hui Zhang,Jian Deng,Yibo He,Zhili Cai,Yitao He
Background Ischemic stroke (IS) is known for its high incidence, disability, and mortality, and there is an urgent need to investigate the pathophysiological mechanisms and develop novel treatment strategies. Objectives We aimed to investigate the mechanisms of the novel circMap2k1/miR-135b-5p/Pidd1 axis in the treatment of IS progression with fluoxetine. Methods The middle cerebral artery occlusion (MCAO) model was done in adult male Sprague–Dawley (SD) rats and followed by fluoxetine treatment and the injection of adeno-associated virus (AAV)-sh-ctr and AAV-sh-circMap2k1 into the bilateral hippocampal tissues of rats. Dual-luciferase reporter gene assay was employed to confirm the binding between miR-135b-5p and Pidd1. Enzyme-linked immunosorbent assay was performed to measure the concentrations of the inflammatory factors TNF-α, IL-6, and IL-1β in the plasma. The role of circMap2k1 in cells was tested by overexpression of circMap2k1. Cell viability was assessed using Cell Counting Kit-8 assay, while apoptosis was measured by flow cytometry. Results Knockdown of circMap2k1 enhanced the therapeutic and protective effect of fluoxetine on IS injury in rats. Dual-luciferase reporter gene assay confirmed the targeting of miR-135b-5p to Pidd1. Additionally, fluoxetine deactivated the adsorption of miR-135b-5p by downregulating circMap2k1, and miR-135b-5p further exerted its inhibitory effect on Pidd1 and finally attenuated the inflammatory response caused by microglial polarization after IS. Cell experiments revealed that overexpression of circMap2k1 repressed cell viability and promoted cell apoptosis. Conclusions Fluoxetine downregulated of circMap2k1 was associated ameliorate neurological injury and inflammatory responses induced by microglial polarization after IS. The manuscript is available as a preprint at this link: doi.org/10.21203/rs.3.rs-3209057/v1 .
研究领域:
神经科学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
REACTIVE & FUNCTIONAL POLYMERS
·
2024
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IF 4.5
Yanbo Tian,Liju Tan,Huiru Li,Yu Qiao,Na Wang,Jiangtao Wang
Magnetic molecular imprinted polymers (MMIPs) for specific adsorption of fluoxetine hydrochloride (FXT) were prepared by using a new solvent, deep eutectic solvents (DESs) as the porogen, magnetic Fe 3 O 4 nanoparticles modified twice as the carrier and methacrylic acid (MAA) as the functional monomer. The effects of DESs type, molar ratio of functional monomer to template molecule and amount of crosslinker on the adsorption properties of MMIPs were investigated. The characterization results showed that the optimized MMIPs is a rough porous material with a particle size between 300 and 500 nm, and the magnetic properties and thermal properties are satisfactory. The adsorption of MMIPs for FXT reached the equilibrium within 30 min. The equilibrium absorption capacity was 38.54 mg·g −1 with an imprinting factor of 1.88. The constructed MMIPs showed good specificity and reusability. A rapid, simple and economical detection method for residual FXT in environmental water samples was established with the recovery rate between 94.4 and 102.2 %, and LOD and LOQ of 4.0 μg·L −1 and 1.2 μg·L −1 , respectively.
研究领域:
材料科学
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环境科学
·
分析化学
✓ 已验证
产品关联
DOI
高影响因子
BRAIN RESEARCH BULLETIN
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2020
·
IF 3.37
Zuotian Wu,Gaohua Wang,Huiling Wang,Ling Xiao,Yanyan Wei,Can Yang
Background Recent studies indicate that antidepressants treatment restores neuronal plasticity. In contrast, some researchers claim that serotonergic antidepressants, including fluoxetine (FLU), may exacerbate neuronal plasticity, which is contradictory and rarely studied. Since almost those studies exposed cells with drugs for 1–2 days as treatment models of antidepressants, it is possible that FLU exposure for longer periods would have opposite effects on neuronal plasticity. Results In the present study, we examined the effects of FLU exposure (up to 3 days) on the neuronal plasticity in differentiated PC12 cells. The cell viability shown a slight decrease at day 2 (93.5 ± 3.5 %), followed by a highly significant decrease at day 3(71.4 ± 4.4 %). As previously reported, neuronal plasticity was significantly upregulated by FLU exposure at day 1. However, the neurite length, activity-regulated cytoskeleton-associated protein (Arc) and c-Fos mRNA were inhibited with FLU exposure at day 3. Similarly, the expression of tubulin, which play important roles in the neuronal plasticity, was the same result. Furthermore, we found α-tubulin interacted with collapsing response mediator protein 2(CRMP2), which is related to neuronal plasticity, and the regulation of CRMP2 activity influenced the neurite length, Arc, c-Fos and tubulin expression. Conclusions The results demonstrated that neuronal plasticity was increased by FLU exposure at day 1, but exposure with FLU for more than 2 days had opposite effect on it. The reduction in neuronal plasticity with FLU exposure for more than 2 days might be involved in some aspects of the therapeutic effect of antidepressant on depression.
研究领域:
神经科学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ALLOYS AND COMPOUNDS
·
2023
·
IF 6.2
Aiting Chen,Yanping Wei,Du Tuo,Chuanqin Zhou,Shuting Shi,Nana Tang,Quanguo He,Jun Liu
A facile and novel electrochemical determination of Fluoxetine (FLX) at submicromolar concentration Niobium carbide (Nb 2 CT x ) and Nitrogen-doped Reduced Graphene Oxide (NRGO) hybridized electrodes as sensing platform is demonstrated. Herein, Niobium carbide (Nb 2 CT x ) was successfully prepared by etching Nb 2 AlC and then ultrasonically compounded with Nitrogen-doped Reduced Graphene Oxide (NRGO), to form a well-dispersed Nb 2 CT x /NRGO composite, which was modified onto a glassy carbon electrode (GCE). The morphology, structure and electrochemical property of the Nb 2 CT x /NRGO/GCE was characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). The electrocatalytic activity of the Nb 2 CT x /NRGO/GCE for FLX oxidation was studied in detail. The peak currents showed two good linear relationships (R 2 = 0.9962 and 0.9949) with FLX concentrations (1.0–10 µM and 10–100 µM) and a detection limit of 0.34 µM (S/N = 3). The sensor has good selectivity, repeatability, reproducibility and stability, and is capable of sensitively determining FLX in human serum and urine samples of clinical biological fluids. This work is believed to be of great significance and of broad interest for research on innovative MXene materials development and biomedical sensing applications.
研究领域:
材料科学
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生物医学工程
·
分析化学
✓ 已验证
产品关联
DOI
高影响因子
NEUROREPORT
·
2013
·Vol. 24
·期 12
·682
·
IF 1.404
Wang Guohua,Cheng Yufang,Gong Meifang,Liang Baofang,Zhang Mingzi,Chen Yupin,Zhang Cong,Yuan Xin,Xu Jiangping
Unraveling the pathophysiological basis for the development of and recovery from depression is a unique challenge. Dendritic plasticity has been reported to be involved in the development of depression. We modeled an anxiety/depression-like phenotype by chronic corticosterone exposure in mice and reversed this anxiety/depression-like phenotype by long-term treatment with fluoxetine (FLX). Spine density in the hippocampus was detected by Golgi–Cox staining at five time points. The data showed that 35 days of corticosterone exposure led to a decrease in spine density in CA1, concomitant with the onset of depression. Following 25 days of treatment with FLX, the decrease in both the dendritic spine density in the hippocampus and the anxiety/depression-like phenotype induced by chronic corticosterone recovered to normal levels concomitantly. Interestingly, the total spine density changes are all mainly driven by changes in thin and stubby spines, not mushroom spines, following chronic corticosterone or FLX treatment. Our results suggest that the changes in dendritic spine density in the hippocampus may be one of the pathophysiological mechanisms underlying the development of and recovery from depression, and the neuronal plasticity of CA1 is first impaired during the development of depression.
研究领域:
神经科学
·
精神医学
✓ 已验证
DOI
PubMed
高影响因子
Bioengineered
·
2022
·
IF 6.832
Yazhou Sun,Weiguo Wan,Xin Zhao,Xueyu Han,Tianxin Ye,Xiaoli Chen,Qian Ran,Xiukun Wang,Xin Liu,Chuan Qu,Shaobo Shi,Cui Zhang,Bo Yang
Sigma 1 receptor (S1R) has shown a preferable protective effect on left ventricular function, but whether it protects right ventricular (RV) function is still elusive.This study aimed to determine the effects of S1R on RV dysfunction secondary to pulmonary arterial hypertension.Sixty wild-type male Sprague–Dawley rats were randomly divided into the control group, the fluvoxamine group, the pulmonary arterial hypertension group and the pulmonary arterial hypertension combined with fluvoxamine group. Monocrotaline (60 mg/kg) was administered to induce pulmonary arterial hypertension, and fluvoxamine was given for 21 consecutive days to activate S1R after one week of monocrotaline administration. Echocardiographic, serologic, and histologic parameters, qRT-PCR, and western blotting were conducted after 4 weeks of monocrotaline administration.The expression of S1R was decreased in the right ventricle in pulmonary arterial hypertension. TAPSE, and the FAC of the right ventricle were significantly decreased, and RV EDP and the plasma concentration of N-terminal pro-B-type natriuretic peptide was increased in the pulmonary arterial hypertension group, but fluvoxamine partly restored those abnormalities (all P < 0.05). Moreover, pulmonary arteriole remodeling, and fibrosis and hypertrophy in the RV were shown in the pulmonary arterial hypertension group; interestingly, fluvoxamine recovered RV structural remodeling (all P < 0.05) but neither alleviated pulmonary arteriole remodeling nor reduced pulmonary artery pressure. Furthermore, S1R activation protects RV function by upgrading the NRF 2/HO 1-mediated antioxidant stress pathway. In conclusion, chronic S1R activation ameliorates structural remodeling and RV dysfunction secondary to pulmonary arterial hypertension without altering pulmonary artery pressure.
研究领域:
心脏病学
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药理学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
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