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MOLECULES · 2023 ·Vol. 28 ·期 14 ·5496 · IF 4.6

The Effect of Bergenin on Isonicotinic Acid Hydrazide and Rifampicin-Induced Liver Injury Revealed by RNA Sequencing

Ting Li,Chaoyue Yang,Houkang Cao,Siyi Mo,Bo Li,Zhipeng Huang,Ruobing Zhang,Jianzhao Wu,Kefeng Zhang,Ya Gao

Bergenin (BER), a natural component of polyphenols, has a variety of pharmacological activities, especially in improving drug metabolism, reducing cholestasis, anti-oxidative stress and inhibiting inflammatory responses. The aim of this study was to investigate the effects of BER on liver injury induced by isonicotinic acid hydrazide (INH) and rifampicin (RIF) in mice. The mice model of liver injury was established with INH (100 mg/kg)+RIF (100 mg/kg), and then different doses of BER were used to intervene. The pathological morphology and biochemical indicators of mice were detected. Meanwhile, RNA sequencing was performed to screen the differentially expressed genes and signaling pathways. Finally, critical differentially expressed genes were verified by qRT-PCR and Western blot. RNA sequencing results showed that 707 genes were significantly changed in the INH+RIF group compared with the Control group, and 496 genes were significantly changed after the BER intervention. These differentially expressed genes were mainly enriched in the drug metabolism, bile acid metabolism, Nrf2 pathway and TLR4 pathway. The validation results of qRT-PCR and Western blot were consistent with the RNA sequencing. Therefore, BER alleviated INH+RIF-induced liver injury in mice. The mechanism of BER improving INH+RIF-induced liver injury was related to regulating drug metabolism enzymes, bile acid metabolism, Nrf2 pathway and TLR4 pathway.Keywords:bergenin;isonicotinic acid hydrazide;rifampicin;liver injury;RNA sequencing

CAS / MDL: 54-85-3 13292-46-1
研究领域: 药理学 · 分子生物学 · 毒理学
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EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES · 2020 · IF 3.616

A new cocrystal of isoniazid-quercetin with hepatoprotective effect: The design, structure, and in vitro/in vivo performance evaluation

Fang Liu,Ling-Yang Wang,Ming-Chao Yu,Yan-Tuan Li,Zhi-Yong Wu,Cui-Wei Yan

With the purpose of overcoming the serious hepatotoxicity of antituberculosis drug isoniazid (INH), a cocrystallization strategy based on complementary advantages was implemented by choosing the hepatoprotective nutraceutical quercetin (QCT) as the cocrystal former. The strategy plays the solubility advantage of INH to improve the bioavailability of the insoluble QCT, thereby significantly enhancing the QCT's hepatoprotective effects. The optimized protective effects of QCT, in turn, feed back to INH to reduce its hepatotoxicity. Along this line, a novel INH-QCT cocrystal was successfully prepared and structurally characterized. The systematic evaluation results of the in vitro/in vivo revealed that, due to the advantage of INH's solubility, the dissolution efficiency of QCT from the cocrystal was increased 51.67-fold compared with that of coarse quercetin, and the oral bioavailability of the cocrystal in rats was enhanced by 28.91 times. As a result, the INH-QCT cocrystal almost removed INH induced serious hepatotoxicity, which has been demonstrated by the hepatotoxicity studies in rats. These findings present new opportunities for the advantageous solid forms of low-toxic antituberculosis drugs, and open new avenues against toxic side effects of drugs through the cocrystallization mean.

CAS / MDL: 54-85-3
研究领域: 药学 · 医学
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Analytical Methods · 2023 ·Vol. 15 ·期 7 ·944-950 · IF 3.1

Green synthesis of CQDs for determination of iron and isoniazid in pharmaceutical formulations

Wenzhan Yu,Qian Li,Liqiong He,Renlong Zhou,Lifu Liao,Jinhua Xue,Xilin Xiao

Camphor leaves were used as the precursor for the hydrothermal synthesis of carbon quantum dots. The preparation method is simple and rapid, and the raw material is environmentally friendly and easy to obtain. Without additional modification, the carbon quantum dots were used as fluorescent probes for the sensitive and selective detection of Fe3+ and isoniazid at different excitation wavelengths. For Fe3+, at the excitation wavelength of 320 nm, the ratio of fluorescence intensity of CQD solution after adding Fe3+ to CQD solution without Fe3+ addition, F/F0, and Fe3+ concentration showed a good linear relationship in the range of 2.72 × 10−5 to 1.00 × 10−4 mol L−1 (R2 = 0.9912), and the limit of detection was 8.16 μmol L−1. For isoniazid, at the excitation wavelength of 270 nm, the ratio of fluorescence intensity of CQDs solution with isoniazid to CQDs solution without isoniazid, F/F0, and isoniazid concentration showed good linear relationships in the range of 3.81 × 10−6 to 1.00 × 10−5 mol L−1 (R2 = 0.9941) and 1.00 × 10−5 to 2.10 × 10−4 mol L−1 (R2 = 0.9910) respectively, and the limit of detection was 1.14 μmol L−1. A fluorescence method for the determination of Fe and isoniazid content was proposed. The method has been used to detect iron in iron supplement tablets and isoniazid in isoniazid tablets with satisfactory results.

研究领域: 分析化学 · 药物分析 · 环境科学
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International Journal of Electrochemical Science · 2023 · IF 1.5

A Novel Electrochemiluminescence Modified Glasss Carbon Electrode Based on Carboxylated Acetylene Black / Ru(bpy)32+ / Nafion for Detection of Isoniazid

Jing-yi Jiang,Qingyi Li,Wen-chang Wang,Xiao-hui Chen,Zhi-dong Chen

A novel, rapid, and facile electrochemiluminescence sensor which based on carboxylated acetylene black / Ru(bpy) 3 2+ / nafion modified glass carbon electrode (CAB/Ru(bpy) 3 2+ /NAF/GCE) was developed for detecting isoniazid (INH). The CAB/Ru(bpy) 3 2+ /NAF/GCE expresses an efficient electrochemiluminescence response for INH, because of the brilliant luminous efficiency of Ru(bpy)32+ and admirable electronic transmission of acetylene black. The electrochemiluminescence intensity was quenched significantly with addition of INH. Under the optimal conditions, the sensor for the detection of isoniazid exhibits a wide linear range of 1.0 × 10 -6 ~ 1.0 × 10 -3 mol·L -1 with the detection limit of 5.0 × 10 -7 mol·L -1 . The sensor is expected to be a simple and convenient method for the determination of INH in pharmaceutical samples .

研究领域: 分析化学 · 药物分析
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JOURNAL OF MOLECULAR LIQUIDS · 2017 · IF 3.648

An example of green copper corrosion inhibitors derived from flavor and medicine: Vanillin and isoniazid

Shi Mo,Ling Jie Li,Hong Qun Luo,Nian Bing Li

The use of some industrial materials such as medicine and flavor in the anti-corrosion field is an attractive topic. A Schiff base ( N -isonicotinamido-3-methoxy-4-hydroxybenzalaldimine, IM) based on flavor (vanillin) and medicine (isoniazid) has been synthesized and utilized as a green corrosion inhibitor for copper in NaCl media. Electrochemical techniques are employed to analyze its inhibition property. The copper surface is characterized by scanning electron microscopy, infrared spectroscopy , and energy-dispersive X-ray spectroscopy. IM acts as an anodic inhibitor and its inhibition efficiency is up to 93% at 120   mg/L and more remarkable than its corresponding reactants. With a large molecular surface area and better electron donation ability, IM has a better corrosion inhibition performance and may be adsorbed on the copper surface through NH and C N groups, according to theoretical studies.

CAS / MDL: 121-33-5 54-85-3
研究领域: 材料科学 · 电化学 · 表面科学
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JOURNAL OF MOLECULAR LIQUIDS · 2022 · IF 6.633

Mechanistic studies on the oxidation reaction of antitubercular drug isoniazid and its analogy hydrazides by chlorine dioxide over a wide pH range

Yang Liu,Hongqian Xi,Jinhu Wang,Jie Fu,Tiesheng Shi

Oxidations of the antitubercular drug isoniazid (INH) and its analogy hydrazides, nicotinic hydrazide (NH), picolinoyl hydrazide (PH), and benzohydrazide (BH), by ClO 2 were investigated with a focus on the kinetics and reaction mechanisms. In buffered solutions of a wide pH range (from 0.51 to 10.35), the oxidation reactions strictly followed the second-order kinetics, and the apparent second-order rate constant k app versus pH profiles were established at 25.0 °C and 1.0 M ionic strength. Excess ClO 2 could rapidly oxidize the hydrazides to their corresponding aryl acids which were identified by mass spectrometry. For each of the hydrazides, the proposed reaction mechanism involves parallel rate-determining reactions between ClO 2 and various protolysis species of the hydrazide, rendering two types of hydrazyl free radicals; the free radicals are quickly oxidized by 3 more equivalents of ClO 2 to aryl acids. The derived rate constants for the rate-determining reactions revealed that for each hydrazide a huge reactivity difference existed among the protolysis species (>10 8 times) and that the enolate form (or its resonant structures) was extremely reactive. Two possible modes of electron transfer in the rate-determining reactions are discussed based on the observed reaction characters. In buffered solution of pH 7.0 and 25.0 °C, the measured values of k app are 6.20×10 4 , 7.8×10 3 , 2.57×10 3 , and 1.83×10 3 M −1 s −1 for INH, NH, PH, and BH, respectively, imparting an important data set as a reference to the water treatment. This work may open a new door for resolving water pollution caused by INH and its derivatives.

研究领域: 药理学 · 环境科学
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JOURNAL OF ELECTROANALYTICAL CHEMISTRY · 2022 · IF 4.598

Significantly enhanced electrochemiluminescence of nalidixic acid/S2O82− system by isonicotinic as Co-reaction accelerator for ultrasensitive detection of tetraethylenepentamine

Panpan Xu,Tingting Xu,Mingguang Ma,Xia Qiu,Yue Wang,Yinggui Zhu

This work presents a method for the establishment of a highly sensitive and selective nalidixic acid and S 2 O 8 2− (NA/S 2 O 8 2− ) electrochemiluminescence (ECL) system using isonicotinic (INH) as a co-reaction accelerator. After optimizing the experimental conditions including scan rate, pH value of buffer solution, concentration, etc., the chemiluminescence mechanism of the system was studied in detail using fluorescence spectroscopy, ECL spectroscopy and cyclic voltammetry (CV). The results show that INH is an efficient co-reaction accelerator, which interacts with the co-reactant S 2 O 8 2− but not the luminophore NA to promote the production of more oxidant SO 4 ·– , which then further reacts with NA to generate excited state species NA* with strong ECL signal, indicating that co-reaction accelerators can provide a simple, efficient, and low-cost method for signal amplification. Based on the great ECL enhancement of INH for the NA/S 2 O 8 2− system, under the optimal experimental conditions, highly sensitive and selective electrochemiluminescence detection of tetraethylenepentamine (TEPA) was achieved.

研究领域: 分析化学 · 药物分析 · 环境科学
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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY · 2020 · IF 3.232

A Redox-induced Dual-mode Colorimetric and Fluorometric Method based on N-CDs and MnO2 for Determination of Isoniazid in Tablets and Plasma Samples

Kuanxia Ma,Lushan Liang,Xie Zhou,Weiguo Tan,Ou Hu,Zuanguang Chen

We develop a simple hydrothermal method to prepare a novel nitrogen-doped carbon dots (N-CDs) originated from green carbon source Liu-bao tea and ethylene diamine. The N-CDs emits strong and stable blue fluorescence (E m  = 440 nm) under the excitation wavelength of 350 nm with a quantum yield of 35%. And it is used as an excellent fluorescent output for the sensitive and visual dual-mode determination of isoniazid. The fluorescence of N-CDs is “turned off” first by manganese dioxide (MnO 2 ) nanosheets due to inner filter effect, MnO 2 nanosheets can also oxidize TMB (3,3',5,5'- tetramethylbenzidine) to blue oxTMB. Isoniazid, however, can reduce MnO 2 nanosheets to Mn 2+ , turning on the fluorescence again. The color of the solution fades from blue to colorless because less TMB can be oxidized. Under the optimal conditions, the dual-mode method has a satisfying linear relationship ranging from 2.0 to 120.0 μM with a limit of detection of 0.7 μM (S/N = 3). And it has been applied successfully to colorimetric and fluorescent determination of isoniazid in tablets and clinical plasma samples, with recoveries ranging from 94.0% to 102.4%. The properties of N-CDs and MnO 2 nanosheets were thoroughly characterized using TEM, FT-IR, XPS, AFM and fluorescence spectrophotometer, the quenching mechanism was also discussed.

研究领域: 分析化学 · 药物分析 · 生物医学
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Applied Nanoscience · 2021 ·Vol. 11 ·期 8 ·2271-2280 · IF 3.674

Electrospun high bioavailable rifampicin–isoniazid-polyvinylpyrrolidone fiber membranes

Liu Yueqi,Li Chenxi,Chen Jia,Han Yufen,Wei Ming,Liu Jun,Yu Xiaomin,Li Fangjun,Hu Ping,Fu Lulu,Liu Yong

Rifampicin (RIF) and Isoniazid (INH) are two first-line drugs for tuberculosis treatment. Compared to isoniazid, rifampicin has poor water solubility, which results in low bioavailability. Combining the two drugs can improve the treatment effect of tuberculosis, but thier direct contact may accelerate the degradation of rifampicin, which is also considered to be another reason for RIF’s low bioavailability. In this study, the polyvinylpyrrolidone (PVP) was selected as the carrier and mixed with the loaded drug of rifampicin and isoniazid separately. The quick-released rifampicin/isoniazid-polyvinylpyrrolidone mingled fibers (RIPMF) were fabricated by the electrospinning method to promote the absorption of rifampicin. The results showed that isoniazid-polyvinylpyrrolidone (INH-PVP) nanofibers and rifampicin-polyvinylpyrrolidone (RIF-PVP) microfibers were mixed in RIPMF, instead of two drugs coexisting in one fiber. Rifampicin and isoniazid in the fibers changed from crystalline to amorphous states, which facilitated the release of the rifampicin from the fibers. The hydrophilicity of RIF-PVP fibers was not distinct, but that of RIPMF increased with the addition of INH-PVP fibers. The release rate of rifampicin in rifampicin-loaded fibers was twice as fast as rifampicin powder. Additionally, in vitro antibacterial test showed that RIPMF had an obvious inhibition effect on Staphylococcus aureus . Finally, the rifampicin-loaded fibers enhanced the release rate of rifampicin and improved its bioavailability. Increased bioavailability reduces the waste of rifampicin and prevents damage to the kidneys due to the massive metabolism of rifampicin in biomedicine.

研究领域: 药学 · 材料科学 · 微生物学
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Analytical Methods · 2014 ·Vol. 7 ·期 2 ·793-798 · IF 1.938

Determination of isoniazid content via cysteic acid/graphene modified glassy carbon electrode

Xiaojing Si,Lin Jiang,Xinyue Wang,Yaping Ding,Liqiang Luo

The electrodeposited graphene (EGR) and cysteic acid (CA) composite (CA/EGR) was fabricated through an electrochemical method for the modification of glassy carbon electrode (GCE). Fourier transform infrared spectroscopy (FT-IR) was carried out to characterize the proposed CA film. The electrochemical performance of the CA/EGR modified GCE (CA/EGR/GCE) was demonstrated with cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The modified GCE was designed to act as an electrochemical sensor for isoniazid. The obtained detection linearity at the CA/EGR/GCE ranged from 0.1 to 200 μM with the detection limit of 0.03 μM (S/N = 3). Moreover, the sensor was employed for practical sample analysis with satisfactory recoveries, further validating the reliable practicability for electroanalysis. In addition, CA/EGR/GCE also displayed good reproducibility, high stability and excellent anti-interference ability for the determination of isoniazid.

CAS / MDL: 54-85-3
研究领域: 药物分析 · 电化学
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ANALYTICAL BIOCHEMISTRY · 2023 · IF 2.9

Isoniazide modified Ag nanoparticles triggered photothermal immunoassay for carcinoembryonic antigen detection

Jiawang Xiang,Bing Zhang,Yani Shi,Yanfei Wen,Yuan Yuan,Jianying Lin,Zhihuan Zhao,Jing Li,Yan Cheng

As the most well-known analytical tool, the thermometer has been extended to the field of biological analysis based on the photothermal effect. Herein, isoniazide modified Ag nanoparticles were prepared as nanolabels to build an immunoassay . The nanoparticles were characterized by transmission electron microscope (TEM), dynamic laser scattering (DLS), X-ray powder diffraction (XRD), and Fourier transform infrared (FT-IR). When the target protein was present, the sandwich immunoassay was developed and the photothermal reaction was triggered by isoniazide modified Ag nanoparticles. As a reducing agent, isoniazide is used to transform phosphomolybdic acid hydrate into molybdenum blue solution. And molybdenum blue had good photothermal stability and high photothermal conversion efficiency. The temperature variation of molybdenum blue solution showed a positive correlation with the concentration of carcinoembryonic antigen (CEA). Thus, the target protein of CEA was quantitative detection by thermometer. The linear response range is 0.1 ng mL −1 to 40 ng mL −1 , and the detection limit is 0.08 ng mL −1 . Moreover, the proposed protocol had satisfactory selectivity, accuracy, and reproducibility.

研究领域: 纳米技术 · 生物医学工程 · 分析化学 · 癌症研究
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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS · 2018 · IF 2.831

Determination of an isonicotinylhydrazide derivative, a novel positive inotropic compound, in mouse plasma by LC–MS/MS and its application to a pharmacokinetics study

Renjie Hui,Yueying Gao,Jingyi Liu,Haili Liu,Chunlei Tang,Bainian Feng

Heart failure (HF) is one of the most serious health problems worldwide. A new positive inotropic compound, an isonicotinylhydrazide derivative (AF-HF001) was designed recently. A liquid chromatography-tandem mass spectrometry (LC–MS/MS) method was developed for the determination of the target analyte in mouse plasma. Samples were prepared by one step precipitation with ethyl acetate and stored in acetonitrile. Chromatographic analysis was carried out on a Hypersil Gold C 18 column (2.1 mm × 50 mm, 3 μm) with a gradient mobile phase consisting of acetonitrile and 0.1% aqueous formic acid. The analyte was detected by selective reaction monitoring (SRM) mode with target quantitative ion pair of m/z 292.1 → 148.2, using praziquantel as the internal standard (IS) m/z 313.1 → 203.2. Good linearity ( r  = 0.995) was observed over a wide concentration range. The validation of method showed acceptable recovery and precision. The method has been then applied to a very first pharmacokinetic assay of AF-HF001 in mice.

研究领域: 药物分析 · 心血管药理学
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