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1.
J Biomed Opt ; 25(1): 1-11, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31849205

RESUMO

Hemozoin, the heme detoxification end product in malaria parasites during their growth in the red blood cells (RBCs), serves as an important marker for diagnosis and treatment target of malaria disease. However, the current method for hemozoin-targeted drug screening mainly relies on in vitro ß-hematin inhibition assays, which may lead to false-positive events due to under-representation of the real hemozoin crystal. Quantitative in situ imaging of hemozoin is highly desired for high-throughput screening of antimalarial drugs and for elucidating the mechanisms of antimalarial drugs. We present transient absorption (TA) imaging as a high-speed single-cell analysis platform with chemical selectivity to hemozoin. We first demonstrated that TA microscopy is able to identify ß-hematin, the artificial form of hemozoin, from the RBCs. We further utilized time-resolved TA imaging to in situ discern hemozoin from malaria-infected RBCs with optimized imaging conditions. Finally, we quantitatively analyzed the hemozoin amount in RBCs at different infection stages by single-shot TA imaging. These results highlight the potential of TA imaging for efficient antimalarial drug screening and drug mechanism investigation.

2.
Nat Commun ; 10(1): 5318, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31754221

RESUMO

Stimulated Raman scattering (SRS) microscopy allows for high-speed label-free chemical imaging of biomedical systems. The imaging sensitivity of SRS microscopy is limited to ~10 mM for endogenous biomolecules. Electronic pre-resonant SRS allows detection of sub-micromolar chromophores. However, label-free SRS detection of single biomolecules having extremely small Raman cross-sections (~10-30 cm2 sr-1) remains unreachable. Here, we demonstrate plasmon-enhanced stimulated Raman scattering (PESRS) microscopy with single-molecule detection sensitivity. Incorporating pico-Joule laser excitation, background subtraction, and a denoising algorithm, we obtain robust single-pixel SRS spectra exhibiting single-molecule events, verified by using two isotopologues of adenine and further confirmed by digital blinking and bleaching in the temporal domain. To demonstrate the capability of PESRS for biological applications, we utilize PESRS to map adenine released from bacteria due to starvation stress. PESRS microscopy holds the promise for ultrasensitive detection and rapid mapping of molecular events in chemical and biomedical systems.

3.
Dalton Trans ; 48(46): 17258-17265, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31710322

RESUMO

The development of effective bifunctional catalysts for both oxygen reduction reactions (ORRs) and oxygen evolution reactions (OERs) is crucial for improving the performance of charge and discharge processes in rechargeable metal-air batteries. Here, we report a sulfonated cobalt phthalocyanine/carbon nanotube hybrid (CoPc-SO3H/CNT) prepared by a facile anchoring method along with sonication and magnetic stirring. The resulting CoPc-SO3H/CNT hybrid exhibits better catalytic activity for ORRs and OERs than the cobalt phthalocyanine/carbon nanotube hybrid (CoPc/CNT), sulfonated cobalt phthalocyanine (CoPc-SO3H), cobalt phthalocyanine (CoPc) and the carbon nanotube (CNT). The onset potential of CoPc-SO3H/CNT for the ORR in 0.1 M KOH is 0.88 V (vs. RHE), which is higher than that of CoPc/CNT (0.85 V), the CNT (0.80 V), CoPc-SO3H (0.77 V) and CoPc (0.66 V). Meanwhile, the CoPc-SO3H/CNT hybrid shows a much lower OER potential (1.62 V) at a current density of 10 mA cm-2 compared to CoPc-SO3H (1.64 V), CoPc/CNT (1.74 V), the CNT (1.96 V) and CoPc (>2.00 V) in 1 M KOH. Similar patterns are also found in 0.1 M KOH solution. Both the conductive CNT and the electron-withdrawing sulfonic groups are confirmed to benefit the electrochemical oxygen reactions (ORRs/OERs).

4.
J Phys Chem Lett ; 10(15): 4374-4381, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31313926

RESUMO

Voltage imaging allows mapping of the membrane potential in living cells. Yet, current intensity-based imaging approaches are limited to relative membrane potential changes, missing important information conveyed by the absolute value of the membrane voltage. This challenge arises from various factors affecting the signal intensity, such as concentration, illumination intensity, and photobleaching. Here, we demonstrate electronic preresonance hyperspectral stimulated Raman scattering (EPR-hSRS) for spectroscopic detection of the membrane voltage using a near-infrared-absorbing microbial rhodopsin expressed in E. coli. This newly developed near-infrared active microbial rhodopsin enables electronic preresonance SRS imaging at high sensitivity. By spectral profiling, we identified voltage-sensitive SRS peaks in the fingerprint region in single E. coli cells. These spectral signatures offer a new approach for quantitation of the absolute membrane voltage in living cells.


Assuntos
Rodopsinas Microbianas/química , Análise Espectral Raman/métodos , Escherichia coli/metabolismo , Concentração de Íons de Hidrogênio , Raios Infravermelhos , Potenciais da Membrana , Mutação , Rodopsinas Microbianas/genética , Rodopsinas Microbianas/metabolismo , Análise de Célula Única/métodos
5.
Anal Chem ; 91(11): 7070-7077, 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31063356

RESUMO

Raman imaging is a promising technique that allows the spatial distribution of different components in the sample to be obtained using the molecular fingerprint information on individual species. However, the imaging speed is the bottleneck for the current Raman imaging methods to monitor the dynamic process of living cells. In this paper, we developed an artificial intelligence assisted fast Raman imaging method over the already fast line scan Raman imaging method. The reduced imaging time is realized by widening the slit and laser beam, and scanning the sample with a large scan step. The imaging quality is improved by a data-driven approach to train a deep convolutional neural network, which statistically learns to transform low-resolution images acquired at a high speed into high-resolution ones that previously were only possible with a low imaging speed. Accompanied with the improvement of the image resolution, the deteriorated spectral resolution as a consequence of a wide slit is also restored, thereby the fidelity of the spectral information is retained. The imaging time can be reduced to within 1 min, which is about five times faster than the state-of-the-art line scan Raman imaging techniques without sacrificing spectral and spatial resolution. We then demonstrated the reliability of the current method using fixed cells. We finally used the method to monitor the dynamic evolution process of living cells. Such an imaging speed opens a door to the label-free observation of cellular events with conventional Raman microscopy.

6.
Shanghai Kou Qiang Yi Xue ; 28(1): 67-70, 2019 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-31081003

RESUMO

PURPOSE: To investigate the correlation between the expression of lncRNA PCAT-1 and clinicopathological features of oral squamous cell carcinoma. METHODS: In this study, 112 oral tissue specimens, including 60 oral squamous cell carcinoma, and 52 non-cancer oral tissues were collected from Department of Stomatology in Anhui Provincial Hospital during 2013 to 2016. Reverse transcription quantitative PCR (RT-PCR) was performed to detect the expression of PCAT-1 and c-Myc. The correlation between the levels of PCAT-1 and clinical features (age, gender, high risk habit, histological stage, cervical lymphatic metastasis, differentiation) were analyzed. Graphpad Prism 7.0 software package was used for statistical analysis. RESULTS: Significant different levels of PCAT-1 were found between the high risk habit (alcohol and tobacco) group and low risk habit group, between patients with cervical lymphnode metastasis and patients without cervical lymphnode metastasis. The expression of PCAT-1 and c-Myc were up-regulated in OSCC, and there were positive correlation between the expression of PCAT-1 and c-Myc; up-regulated expression of PCAT-1 may be associated with higher morbidity of OSCC. CONCLUSIONS: PCAT-1 is overexpressed in oral squamous cell carcinoma and is associated with higher morbidity of OSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Bucais , RNA Longo não Codificante , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/metabolismo , Humanos , Linfonodos , Metástase Linfática , Morbidade , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/metabolismo , Prognóstico , RNA Longo não Codificante/metabolismo
7.
Anal Chem ; 91(13): 8383-8389, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31140782

RESUMO

Intracellular pH is an important modulator of cell functions, and its subtle change may dramatically affect the cellular activities and cause diseases. A reliable imaging of the intracellular pH is still a great challenge. We imaged the intracellular pH during the cell cycle at the single living cell level using newly designed cell-penetrating peptide conjugated pH nanosensors on a home-built in situ microscopic cell culture platform. The conjugated cell-penetrating peptide greatly enhanced the uptake of nanosensors without sacrificing the pH response. We observed a gradual alkalization from interphase to prophase and rapid acidification from prometaphase to telophase, reflecting variation and consumption of the species related to the energy storage during cell cycle. We realized SERS-based pH and fluorescence dual-mode imaging when the pH sensor was further modified with fluorescence dye. The integration of SERS imaging with in situ microscopic cell culture system offers great opportunity for revealing the intracellular pH-related biological and pathological processes.

8.
Anal Chem ; 91(4): 2831-2837, 2019 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-30663310

RESUMO

Electrochemical interfaces determine the performance of electrochemical devices, including energy-related systems. An in-depth understanding of the heterogeneous interfaces requires in situ techniques with high sensitivity and high temporal and spatial resolution. We develop here an electrochemical reflective absorption microscope (EC-RAM) by using the absorption signals of reacting species with a reasonably good spatial resolution and high sensitivity. We systematically study the response of absorbance ( A) and its derivative, i.e. d A/d t, at different positions of the electrode surface and at electrodes with different sizes (50 µm, 500 µm, and 2 mm) both experimentally and theoretically. We find that the derivative cyclic voltabsorptometry (DCVA) frequently used to obtain the local current response in conventional electrochemical optical microscopy techniques is only applicable to reactions of surface species or solution species under linear diffusion control. For processes when the radial diffusion cannot be ignored, as in the case of a microelectrode or the edge of a large electrode, the DCVA curves show distinct diffusion behaviors for the electroactive species in different regions of the electrode, which cannot be directly related to the CV curves. When the radial diffusion dominates the reaction, CVA curves follow the same shape as the CV curves. The developed EC-RAM technique can be applied to extract in situ the local response of an electrochemical system during the dynamic reaction processes.

9.
J Am Chem Soc ; 140(42): 13680-13686, 2018 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-30280886

RESUMO

Precise measurement of the temperature right at the surface of thermoplasmonic nanostructures is a grand challenge but extremely important for the photochemical reaction and photothermal therapy. We present here a method capable of measuring the surface temperature of plasmonic nanostructures with surface-enhanced Raman spectroscopy, which is not achievable by existing methods. We observe a sensitive shift of stretching vibration of a phenyl isocyanide molecule with temperature (0.232 cm-1/°C) as a result of the temperature-dependent molecular orientation change. We develop this phenomenon into a method capable of measuring the surface temperature of Au nanoparticles (NPs) during plasmonic excitation, which is validated by monitoring the laser-induced desorption process of the adsorbed CO on Au NP surface. We further extend the method into a more demanding single living cell thermometry that requires a high spatial resolution, which allows us to successfully monitor the extracellular temperature distribution of a single living cell experiencing cold resistance and the intracellular temperature change during the calcium ion transport process.

10.
Small ; 14(24): e1702883, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29707887

RESUMO

With the serious impact of fossil fuels on the environment and the rapid development of the global economy, the development of clean and usable energy storage devices has become one of the most important themes of sustainable development in the world today. Supercapacitors are a new type of green energy storage device, with high power density, long cycle life, wide temperature range, and both economic and environmental advantages. In many industries, they have enormous application prospects. Electrode materials are an important factor affecting the performance of supercapacitors. MnO2 -based materials are widely investigated for supercapacitors because of their high theoretical capacitance, good chemical stability, low cost, and environmental friendliness. To achieve high specific capacitance and high rate capability, the current best solution is to use MnO2 and carbon composite materials. Herein, MnO2 -carbon composite as supercapacitor electrode materials is reviewed including the synthesis method and research status in recent years. Finally, the challenges and future development directions of an MnO2 -carbon based supercapacitor are summarized.

11.
Chem Rev ; 118(10): 4946-4980, 2018 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-29638112

RESUMO

Surface-enhanced Raman spectroscopy (SERS) inherits the rich chemical fingerprint information on Raman spectroscopy and gains sensitivity by plasmon-enhanced excitation and scattering. In particular, most Raman peaks have a narrow width suitable for multiplex analysis, and the measurements can be conveniently made under ambient and aqueous conditions. These merits make SERS a very promising technique for studying complex biological systems, and SERS has attracted increasing interest in biorelated analysis. However, there are still great challenges that need to be addressed until it can be widely accepted by the biorelated communities, answer interesting biological questions, and solve fatal clinical problems. SERS applications in bioanalysis involve the complex interactions of plasmonic nanomaterials with biological systems and their environments. The reliability becomes the key issue of bioanalytical SERS in order to extract meaningful information from SERS data. This review provides a comprehensive overview of bioanalytical SERS with the main focus on the reliability issue. We first introduce the mechanism of SERS to guide the design of reliable SERS experiments with high detection sensitivity. We then introduce the current understanding of the interaction of nanomaterials with biological systems, mainly living cells, to guide the design of functionalized SERS nanoparticles for target detection. We further introduce the current status of label-free (direct) and labeled (indirect) SERS detections, for systems from biomolecules, to pathogens, to living cells, and we discuss the potential interferences from experimental design, measurement conditions, and data analysis. In the end, we give an outlook of the key challenges in bioanalytical SERS, including reproducibility, sensitivity, and spatial and time resolution.


Assuntos
Materiais Biocompatíveis/análise , DNA/análise , Nanoestruturas/análise , Proteínas/análise , Análise Espectral Raman/normas , Técnicas Biossensoriais , Humanos , Propriedades de Superfície
12.
Zhongguo Zhong Yao Za Zhi ; 43(3): 478-483, 2018 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-29600611

RESUMO

In this study, an endophytic bacteria strain BZJN1 was isolated from Atractylodes macrocephala, and identified as Bacillus subtilis by physiological and biochemical tests and molecular identification. Strain BZJN1 could inhibit the growth of mycelia of Ceratobasidium sp. significantly, and the inhibition rate was more than 70%. The mycelium growth deformity with bulge as spherical and partially exhaustible in apex or central with microscopic observation. The inhibitory rates under 3% and 6% concentrations of the cell free fermentation were 22.7% and 38.7% expectively. The field test proved that the control efficacy of treatment of 1×108 cfu·mL⁻¹ is 75.27% and 72.37% after 10 and 20 days. All the treatments of strain BZJN1 was able to promote the growth of A. macrocephala, the treatment of 1×108 cfu·mL⁻¹ could able to increase the yield to 14.1%.


Assuntos
Atractylodes/microbiologia , Bacillus subtilis/fisiologia , Basidiomycota/patogenicidade , Agentes de Controle Biológico , Doenças das Plantas/prevenção & controle , Endófitos/classificação , Endófitos/isolamento & purificação , Doenças das Plantas/microbiologia
13.
Toxicology ; 393: 140-149, 2018 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-29129815

RESUMO

Sulphur mustard (2,2'-dichloroethyl sulfide; SM) is a vesicant chemical warfare agent whose mechanism of acute or chronic action is not known with any certainty and to date there is no effective antidote. SM accumulation in adipose tissue (AT) has been originally verified in our previous study. To evaluate the biological effect caused by the presence of abundant SM in adipocyte and assess the biological role of AT in SM poisoning, in vitro and in vivo experiments were performed. High content analysis revealed multi-cytotoxicity in SM exposed cells in a time and dose dependent manner, and adipocytes showed a relative moderate damage compared with non-adipocytes. Cell co-culture model was established and revealed the adverse effect of SM-exposed adipocyte supernatant on the growth of co-cultured cells. The pathological changes in AT from 10mg/kg SM percutaneously exposed rats were checked and inflammation phenomena were observed. The mRNA and protein levels of inflammation-related adipokines secreted from AT in rats exposed to 1, 3 and 10mg/kg doses of SM were determined by reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assays. The expressions of proinflammatory and anti-inflammatory adipokines together promoted the inflammation development in the body. The positive correlations between AT and serum adipokine levels were explored, which demonstrated a substantial role of AT in systemic inflammation responding to SM exposure. Thus, AT is not only a target of SM but also a modulator in the SM toxicity.


Assuntos
Adipócitos/efeitos dos fármacos , Substâncias para a Guerra Química/toxicidade , Gás de Mostarda/toxicidade , Adipócitos/metabolismo , Adipocinas/sangue , Adipocinas/genética , Adipocinas/metabolismo , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Administração Cutânea , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Substâncias para a Guerra Química/farmacocinética , Técnicas de Cocultura , Histonas/metabolismo , Humanos , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Gás de Mostarda/farmacocinética , Membrana Nuclear/efeitos dos fármacos , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Pele/metabolismo , Superóxido Dismutase/metabolismo
14.
Polymers (Basel) ; 10(8)2018 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-30960783

RESUMO

The synthesis of novel branched/star copolymers which possess unique physical properties is highly desirable. Herein, a novel strategy was demonstrated to synthesize poly(ε-caprolactone) (PCL) based miktoarm star (µ-star) copolymers by combining ring-opening polymerization (ROP), styrenics-assisted atom transfer radical coupling (SA ATRC), and atom transfer radical polymerization (ATRP). From the analyses of gel permeation chromatography (GPC), proton nuclear magnetic resonance (¹H NMR), and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), well-defined PCL-µ-PSt (PSt: polystyrene), and PCL-µ-PtBA (PtBA: poly(tert-butyl acrylate) µ-star copolymers were successfully obtained. By using atomic force microscopy (AFM), interestingly, our preliminary examinations of the µ-star copolymers showed a spherical structure with diameters of ca. 250 and 45 nm, respectively. We successfully employed combinations of synthetic techniques including ROP, SA ATRC, and ATRP with high effectiveness to synthesize PCL-based µ-star copolymers.

15.
Rev Sci Instrum ; 88(9): 095110, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28964221

RESUMO

There is an increasing need to study dynamic changing systems with significantly high spatial and temporal resolutions. In this work, we integrated point-scanning, line-scanning, and wide-field Raman imaging techniques into a single system. By using an Electron Multiplying CCD (EMCCD) with a high gain and high frame rate, we significantly reduced the time required for wide-field imaging, making it possible to monitor the electrochemical reactions in situ. The highest frame rate of EMCDD was ∼50 fps, and the Raman images for a specific Raman peak can be obtained by passing the signal from the sample through the Liquid Crystal Tunable Filter. The spatial resolutions of scanning imaging and wide-field imaging with a 100× objective (NA = 0.9) are 0.5 × 0.5 µm2 and 0.36 × 0.36 µm2, respectively. The system was used to study the surface plasmon resonance of Au nanorods, the surface-enhanced Raman scattering signal distribution for Au Nanoparticle aggregates, and dynamic Raman imaging of an electrochemical reacting system.

16.
Nat Commun ; 8: 14891, 2017 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-28348368

RESUMO

Surface-enhanced Raman scattering (SERS) spectroscopy has attracted tremendous interests as a highly sensitive label-free tool. The local field produced by the excitation of localized surface plasmon resonances (LSPRs) dominates the overall enhancement of SERS. Such an electromagnetic enhancement is unfortunately accompanied by a strong modification in the relative intensity of the original Raman spectra, which highly distorts spectral features providing chemical information. Here we propose a robust method to retrieve the fingerprint of intrinsic chemical information from the SERS spectra. The method is established based on the finding that the SERS background originates from the LSPR-modulated photoluminescence, which contains the local field information shared also by SERS. We validate this concept of retrieval of intrinsic fingerprint information in well controlled single metallic nanoantennas of varying aspect ratios. We further demonstrate its unambiguity and generality in more complicated systems of tip-enhanced Raman spectroscopy (TERS) and SERS of silver nanoaggregates.

17.
Zootaxa ; 4365(5): 585-589, 2017 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-29686191

RESUMO

The genus Molpa Walker was previously considered to be disjunctly distributed in broad-leaf rain forests in India and Malaysia. Here we report one new species Molpa dulongensis sp. nov. from subtropic broad-leaf rain forests in southwestern Yunnan Province in China. This is a part of the Indo-Burma biodiversity hotspot area. So we can infer that Molpa is continuously distributed in broad-leaf rain forests found in Oriental Region. Redescription of the genus Molpa and description of the new species Molpa dulongensis sp. nov. are provided. The types are deposited in Insect Collection of Institute of Zoology, Chinese Academy of Sciences, Beijing, China (IZCAS).


Assuntos
Ortópteros , Distribuição Animal , Animais , China , Índia , Malásia , Mianmar
18.
Arch Toxicol ; 91(2): 735-747, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27351766

RESUMO

Sulfur mustard (SM) is a powerful vesicant and one of the most harmful chemical warfare agents. Although having been studied for a long time, it is still difficult to fully elucidate the mechanisms of SM poisoning, and there is no effective antidote or specific treatment for SM injury. The investigations on toxicokinetics and tissue distribution of SM will help to understand its toxicity and provide a theoretical basis for pretreatment and therapy of SM poisoning. But the metabolic trajectory or fate of intact SM in vivo remains unclear, and there are insufficient experimental data to elucidate, due to its high reactivity and difficulty in biomedical sample analysis. In this paper, a sensitive method for the detection and quantification of intact SM in blood or tissues using isotope-dilution LC-MS/MS coupled with chemical conversion was developed. By transforming highly reactive SM into stable derivative product, the real concentration of intact SM in biological samples was obtained accurately. The toxicokinetics and tissue distribution studies of intact SM in rats were successfully profiled by the novel method after intravenous (10 mg/kg) or cutaneous administration (1, 3 and 10 mg/kg). The SM level in blood with peak time at 30-60 min determined in cutaneous exposure experiment was found much higher than previously reported, and the mean residence time in blood extended to 1-1.5 h. A significant accumulation of intact SM was observed in adipose tissues, including the perirenal fat, epididymal fat, subcutaneous fat and brown fat, in which the concentrations of SM were at least 15 times greater than those in non-adipose tissues in cutaneous exposed rats. The recovery of SM in body fat was calculated as 3.3 % of bioavailable SM (the bioavailability after cutaneous exposure was evaluated as 16 %). Thus, the adipose tissue was important for SM distribution and toxicity, which may pioneer a new model for both the prevention and treatment of SM exposure.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Cromatografia Líquida/métodos , Gás de Mostarda/farmacocinética , Gás de Mostarda/toxicidade , Espectrometria de Massas em Tandem/métodos , Animais , Disponibilidade Biológica , Linhagem Celular , Substâncias para a Guerra Química/farmacocinética , Substâncias para a Guerra Química/toxicidade , Humanos , Queratinócitos/efeitos dos fármacos , Masculino , Técnica de Diluição de Radioisótopos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Distribuição Tecidual , Toxicocinética
19.
20.
Artigo em Inglês | MEDLINE | ID: mdl-27322628

RESUMO

Sulfur mustard (SM) is a highly reactive alkylating vesicant with high toxicity and complicated metabolism, the in vivo profile of its oxidation metabolism is not still fully known and urgently needs to be clarified well. In this work, an isotope-dilution high performance liquid chromatography-tandem mass spectrometric method coupled with chemical conversion was developed for the simultaneous quantification of SM and its oxidation products, i.e., mustard sulfoxide (SMO) and mustard sulfone (SMO2). The accurate measurement of SM and its oxidation products with high reaction activity was achived via the method of chemical conversion of 2-(3,5-bis(mercaptomethyl)phenoxy) acetic acid into stable derivative products. Method validation was performed in whole blood matrix, the linear range of the method was between 0.2 and 1000µg/L with correlation coefficients (r(2))>0.99, and the lower limits of quantification for SM, SMO and SMO2 were 1, 1, 0.2µg/L, respectively. The validated method was successfully applied to a toxicokinetics research of SM and its oxidation products after SM dermal exposed rats in a single dose. All three target analytes were found in whole blood samples from poisoned rats, and significant time-dependent responses were also observed. Among them, SMO2 with relatively high toxicity was identified and quantified in vivo for the first time, while SMO was the major product in whole blood and some of them continued to be oxidized to SMO2in vivo. These results give a direct experimental evidence to support that a large amount of SM is converted into the corresponding SMO and SMO2, and these oxidation products might cause potential combined toxic effects.


Assuntos
Substâncias para a Guerra Química/farmacocinética , Gás de Mostarda/farmacocinética , Espectrometria de Massas em Tandem/métodos , Animais , Substâncias para a Guerra Química/análise , Cromatografia Líquida de Alta Pressão/métodos , Limite de Detecção , Masculino , Gás de Mostarda/análogos & derivados , Oxirredução , Ratos Sprague-Dawley , Sulfonas/análise , Sulfonas/sangue , Sulfonas/farmacocinética , Sulfóxidos/análise , Sulfóxidos/sangue , Sulfóxidos/farmacocinética
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