Frontiers in Pharmacology
·
2024
·
IF 4.4
Chen Li,Zhu Ruiqin,Ma Yaxing,Huang Chuixiu,Shen Xiantao
Objective: LC-MS/MS-based metabolomics is an important tool for studying disease-related biomarkers. Conventionally, different strategies have been used to screen biomarkers. However, many studies for biomarker screening by different strategies have ignored the dose-response relationship between the biomarker level and exposure level, and no relevant studies have described and compared different strategies in detail. Phenobarbital (PHB) which belongs to the barbiturates, was selected as the typical representative of neurotoxins. Acylcarnitines have been promising candidates for diagnostic biomarkers for several neurological disorders and neurotoxicity. In this work, we aimed to use an acute PHB poisoning animal model to clarify PHB poisoning effects on plasma and brain acylcarnitine changes and how to rationally analyze data from LC-MS/MS.Methods: The acylcarnitine profiles in plasma and brain regions in an actuate PHB poisoning animal model were utilized. The dose-response relationship between plasma PHB and carnitine and acylcarnitines (CARs) in plasma and brain were assessed by the variance analysis trend test and Spearman’s rank correlation test. In different strategies, principal component analysis (PCA) and partial least squares discriminant analysis (OPLS-DA) screened the differential CARs, variable importance plots (VIPs) were utilized to select putative biomarkers for PHB-induced toxicity, and receiver operating characteristic (ROC) curve analysis then illustrated the reliability of biomarkers.Results: Under the first strategy, 14 potential toxicity biomarkers were obtained including eight downregulated CARs with AUC >0.8. Under the second strategy, 11 potential toxicity biomarkers were obtained containing five downregulated CARs with AUC >0.8. Only when the dose-response relationship was fully considered, different strategies screen for the same biomarkers (plasma acetyl-carnitine (C2) and plasma decanoyl-carnitine (C10)), which indicated plasma acylcarnitines might serve as toxicity biomarkers. In addition, the plasma CAR level changes showed differences from brain CAR level changes, and correlations between plasma CARs and their brain counterparts were weak.Conclusion: We found that plasma C2 and C10 might serve as toxicity biomarkers for PHB poisoning disorders, and PHB poisoning effects on changes in plasma CARs may not be fully representative of changes in brain CARs.
研究领域:
代谢组学
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神经毒理学
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医学
✓ 已验证
DOI
PubMed
高影响因子
Analytical Methods
·
2020
·Vol. 12
·期 6
·813-821
·
IF 2.596
Junbo Liu,Wensi Zhao,Guangyu Wang,Shanshan Tang,Ruifa Jin
Using the density functional theory M062X/6-31G(d,p) method, a molecularly imprinted self-assembly system has been simulated with phenobarbital (PHN) as the imprinted molecule and 4-vinyl pyridine (4-VPY), acrylamide (AM), methacrylic acid (MAA), and itaconic acid (IA) as the functional monomers. The steric configuration, key cooperation binding site, imprinted ratio, and binding energy of the complex have been investigated to obtain the optimal functional monomer. The cross-linking agent was optimized by calculating its binding energy with PHN and IA. The theory of atoms in molecules was used to predict the molecular diagram and Laplace quantity contour map of the stable PHN–IA complex. The imprinting nature between PHN and IA was also discussed. Meanwhile, the selectivity property of PHN–IA stable complex was studied via barbiturate (BAR) and barbiturate acid (BA) as structural analogues. The results showed that, among the four functional monomers, IA is most suitable to form the complex with PHN through hydrogen bond interaction. When the molar ratio between PHN and IA was 1 : 7 and TRIM was the cross-linking agent, the formed complex had the lowest energy and best selectivity to PHN. The maximum apparent adsorption of PHN molecular imprinted polymer (PHN-MIPs) was 16.02 mg g−1 and the maximum dissociation equilibrium constant was 94.97 mg L−1. The selective identification of PHN-MIPs for PHN is higher than for BAR.
研究领域:
药物化学
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计算化学
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材料科学
✓ 已验证
产品关联
DOI
高影响因子
BIOCONTROL SCIENCE AND TECHNOLOGY
·
2017
·
IF 0.919
Xiaohua Hu,Yajie Guo,Songqing Wu,Zhaoxia Liu,Tao Fu,Ensi Shao,Carballar-Lejarazú Rebeca,Guohui Zhao,Zhipeng Huang,Ivan Gelbič,Xiong Guan,Shuangquan Zou,Lei Xu,Lingling Zhang
Bacillus thuringiensis var. israelensis (Bti) is highly pathogenic to mosquito larvae and is widely used for mosquito control. Its mosquitocidal activity however is relatively low compared to many chemical insecticides. The detoxification mechanisms in the mosquito, among other things, might neutralize the Bti activity, resulting in resistance or tolerance. We tested whether or not the detoxification mechanisms against chemical insecticides might also operate against Bti, rendering it less effective. We targeted four enzymes in Aedes aegypti larvae involved in detoxification with inhibitors that have been used in resistance studies in chemical insecticides and assayed their effects on Bti toxicity. Results revealed that phenylmethanesulphonyl fluoride (PMSF), diethyl maleate, phenobarbital (PB), and piperonyl butoxide (PBO) altered Bti toxicity to various degrees. PMSF is a serine protease inhibitor that prevents Bti digestion and improves Bti activity. PB that induces several detoxifying enzymes had two different effects depending on the method of treatment. Mortality was higher when treatment with PB was discontinuous (149%) whereas with continuous treatment it was lower (101%). PBO, a typical cytochrome P450 inhibitor, increased Bti effect (159%). The combination of discontinuous pretreatment of larvae with PB followed by PBO had a synergistic effect and showed increased activity (146%). It appears that the mechanism for Bti resistance in mosquitoes is similar to that of chemical insecticides. Our studies indicate that we may be able to increase Bti activity by inhibiting some of the detoxification systems as active as broad spectrum chemical insecticides.
研究领域:
昆虫学
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毒理学
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杀虫剂抗性
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蚊虫控制
✓ 已验证
产品关联
DOI
高影响因子
ELECTROCHIMICA ACTA
·
2014
·
IF 4.086
Hui Cheng Yu,Xue Yi Huang,Fu Hou Lei,Xue Cai Tan,Yi Chun Wei,Hao Li
Uniform nickel nanoparticles were applied to improve the sensitivity of sensors for phenobarbital (PB) determination. A Ni nanoparticle-modified imprinted electrochemical sensor was developed by thermal polymerization with the use of methacrylic acid as the functional monomer and ethylene glycol maleic rosinate acrylate as the crosslinking agent. The chemical structures and morphologies of the imprinted films were characterized using Fourier transform infrared spectroscopy and scanning electron microscopy. The success of the fabrication of Ni nanoparticles, as well as the Ni nanoparticle-modified imprinted electrochemical sensor, was confirmed by the analytical results. The electrochemical properties of the modified molecularly imprinted and non-imprinted polymer sensors were investigated by cyclic voltammetry, differential pulse voltammetry, electrochemical impedance spectroscopy, and chronoamperometry. Results showed that the electrochemical properties of the molecularly imprinted sensor were remarkably different from those of the non-imprinted sensor. Linear responses of the imprinted sensor to PB were observed for concentrations ranging from 1.4 × 10 −7 mol L −1 to 1.3 × 10 −4 mol L −1 ( r 2 = 0.9976), with a detection limit of 8.2 × 10 −9 mol L −1 (S/N = 3). The imprinted electrochemical sensor was used to determine PB in actual fish samples, in which average recoveries between 95.60% and 104.67% were achieved. The developed Ni nanoparticle-modified electrochemical sensor exhibited high sensitivity, high selectivity, and good recovery.
研究领域:
分析化学
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电化学
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纳米技术
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药物分析
✓ 已验证
产品关联
DOI
高影响因子
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