Generic placeholder image

Current Pharmaceutical Analysis

Editor-in-Chief

ISSN (Print): 1573-4129
ISSN (Online): 1875-676X

Research Article

Metabolic Changes in Rat Plasma After Epilepsy by UPLC-MS/MS

Author(s): Congcong Wen, Caiping Zhou, Yongxi Jin, Yujie Hu, Hongzhe Wang, Xianqin Wang* and Xuezhi Yang*

Volume 17, Issue 5, 2021

Published on: 06 February, 2020

Page: [573 - 583] Pages: 11

DOI: 10.2174/1573412916666200206145207

Price: $65

Abstract

Introduction: Epilepsy is one of the most common neurological diseases in clinical practice. The combined application of metabolomics technology plays a great advantage in the screening of biomarkers.

Methods: In this study, Wistar rats were used as experimental subjects to model intractable epilepsy and to detect the metabolic changes of small molecules in plasma. UPLC-MS/MS was used to determine the small molecules in rat plasma. UPLC HSS C18 (2.1mm×100mm, 1.7 μm) column was used for separation, column temperature of 40°C. The initial mobile phase was acetonitrile -0.3% formic acid with gradient elution, the flow rate was 0.3 mL/min, total running time 4.0 min. Quantitative analysis was performed with multi-response monitoring (MRM).

Results: Compared to the control group, the L-Alanine and L-Arginine decreased in the Epilepsy group (p<0.05); while Cytosine, Adenosine, L-Tyrosine, Citric acid, Fructose increased (p<0.05).

Conclusion: In the screening of epilepsy biomarkers using metabolomics, various amino acids that lead to increased energy production and neurotransmitter imbalance play an important role in epileptic seizures.

Keywords: Epilepsy, plasma, UPLC-MS/MS, amino acid, rat, metabolomics.

Next »
Graphical Abstract

[1]
Nevitt, S.J.; Tudur Smith, C.; Marson, A.G. Phenobarbitone versus phenytoin monotherapy for epilepsy: an individual participant data review. Cochrane Database Syst. Rev., 2019, 7, CD002217.
[http://dx.doi.org/10.1002/14651858.CD002217.pub3] [PMID: 31425629]
[2]
Lukmanji, S.; Manji, S.A.; Kadhim, S.; Sauro, K.M.; Wirrell, E.C.; Kwon, C.S.; Jetté, N. The co-occurrence of epilepsy and autism: A systematic review. Epilepsy Behav., 2019, 98(Pt A), 238-248.
[http://dx.doi.org/10.1016/j.yebeh.2019.07.037] [PMID: 31398688]
[3]
Samia, P.; Hassell, J.; Hudson, J.A.; Murithi, M.K.; Kariuki, S.M.; Newton, C.R.; Wilmshurst, J.M. Epilepsy diagnosis and management of children in Kenya: review of current literature. Res. Rep. Trop. Med., 2019, 10, 91-102.
[http://dx.doi.org/10.2147/RRTM.S201159] [PMID: 31388319]
[4]
Verentzioti, A.; Blumcke, I.; Alexoudi, A.; Patrikelis, P.; Siatouni, A.; Korfias, S.; Sakas, D.; Gatzonis, S. Epileptic patient with mild Malformation of Cortical Development with Oligodendroglial Hyperplasia and Epilepsy (MOGHE): A case report and review of the literature. Case Rep. Neurol. Med., 2019, 2019, 9130780.
[http://dx.doi.org/10.1155/2019/9130780] [PMID: 31281692]
[5]
Xue-Ping, W.; Hai-Jiao, W.; Li-Na, Z.; Xu, D.; Ling, L. Risk factors for drug-resistant epilepsy: A systematic review and meta-analysis. Medicine (Baltimore), 2019, 98(30), e16402.
[http://dx.doi.org/10.1097/MD.0000000000016402] [PMID: 31348240]
[6]
Yan, H.; Katz, J.S.; Anderson, M.; Mansouri, A.; Remick, M.; Ibrahim, G.M.; Abel, T.J. Method of invasive monitoring in epilepsy surgery and seizure freedom and morbidity: A systematic review. Epilepsia, 2019, 60(9), 1960-1972.
[http://dx.doi.org/10.1111/epi.16315] [PMID: 31423575]
[7]
Song, P.; Liu, Y.; Yu, X.; Wu, J.; Poon, A.N.; Demaio, A.; Wang, W.; Rudan, I.; Chan, K.Y. Prevalence of epilepsy in China between 1990 and 2015: A systematic review and meta-analysis. J. Glob. Health, 2017, 7(2), 020706.
[http://dx.doi.org/10.7189/jogh.07.020706] [PMID: 29302325]
[8]
Chen, J.H.; Zhou, X.Q.; Lu, Q.; Jin, L.R.; Huang, Y. New-onset geriatric epilepsy in china: A single-center study. Chin. Med. J. (Engl.), 2018, 131(24), 2915-2920.
[http://dx.doi.org/10.4103/0366-6999.247194] [PMID: 30539903]
[9]
Zhao, Q.; Wang, M.; Kang, H.; Zhu, S. Behavior problems in children with epilepsy and attention-deficit hyperactivity disorder in Central China. Epilepsy Behav., 2018, 89, 79-83.
[http://dx.doi.org/10.1016/j.yebeh.2018.10.001] [PMID: 30388665]
[10]
Yang, K.; Ma, C.; He, Y.; Wang, J.; Yue, Z.; Xiao, B.; Liu, D.; Feng, L. Attitudes toward epilepsy among medical staffs in basic-level hospitals from southern China. Epilepsy Behav., 2018, 89, 23-29.
[http://dx.doi.org/10.1016/j.yebeh.2018.08.024] [PMID: 30384095]
[11]
Li, S.; Chen, J.; Abdulaziz, A.T.A.; Liu, Y.; Wang, X.; Lin, M.; Qin, Y.; Liu, X.; Zhou, D. Epilepsy in China: Factors influencing marriage status and fertility. Seizure, 2019, 71, 179-184.
[http://dx.doi.org/10.1016/j.seizure.2019.07.020] [PMID: 31382137]
[12]
Li, S.; Chen, J.; Tong, X.; Abdulaziz, A.T.A.; Liu, X.; Su, M.; Wang, C.; Li, Z.; Zhou, D. Factors associated with seizure-related motor vehicle accidents among patients with epilepsy in West China. Seizure, 2019, 66, 42-46.
[http://dx.doi.org/10.1016/j.seizure.2019.01.028] [PMID: 30785055]
[13]
Sang, T.; Xiang, T.; Zhu, S.N.; Gao, J.Y.; Jiang, Y.W.; Wu, Y. Treatment-related costs of childhood epilepsy in mainland China: A preliminary study in a tertiary pediatric epilepsy center. J. Child Neurol., 2019, 34(2), 68-73.
[http://dx.doi.org/10.1177/0883073818811176] [PMID: 30484357]
[14]
Yang, L.; Kong, Y.; Dong, X.; Hu, L.; Lin, Y.; Chen, X.; Ni, Q.; Lu, Y.; Wu, B.; Wang, H.; Lu, Q.R.; Zhou, W. Clinical and genetic spectrum of a large cohort of children with epilepsy in China. Genet. Med., 2019, 21(3), 564-571.
[http://dx.doi.org/10.1038/s41436-018-0091-8] [PMID: 29930392]
[15]
Dale, T.; Downs, J.; Olson, H.; Bergin, A.M.; Smith, S.; Leonard, H. Cannabis for refractory epilepsy in children: A review focusing on CDKL5 Deficiency Disorder. Epilepsy Res., 2019, 151, 31-39.
[http://dx.doi.org/10.1016/j.eplepsyres.2019.02.001] [PMID: 30771550]
[16]
Stevelink, R.; Sanders, M.W.; Tuinman, M.P.; Brilstra, E.H.; Koeleman, B.P.; Jansen, F.E.; Braun, K.P. Epilepsy surgery for patients with genetic refractory epilepsy: A systematic review. Epileptic Disord., 2018, 20(2), 99-115.
[http://dx.doi.org/10.1684/epd.2018.0959] [PMID: 29620010]
[17]
Roux, A.; Mellerio, C.; Lechapt-Zalcman, E.; Still, M.; Zerah, M.; Bourgeois, M.; Pallud, J. Left frontal meningioangiomatosis associated with type IIIC focal cortical dysplasia causing refractory epilepsy and literature review. World Neurosurg., 2018, 114, 281-288.
[http://dx.doi.org/10.1016/j.wneu.2018.03.145] [PMID: 29605698]
[18]
Lu, L.; Xiong, W.; Zhang, Y.; Xiao, Y.; Zhou, D. Propofol-induced refractory status epilepticus at remission age in benign epilepsy with centrotemporal spikes: A case report and literature review. Medicine (Baltimore), 2019, 98(27), e16257.
[http://dx.doi.org/10.1097/MD.0000000000016257] [PMID: 31277145]
[19]
Ortiz de la Rosa, J.S.; Ladino, L.D.; Rodríguez, P.J.; Rueda, M.C.; Polanía, J.P.; Castañeda, A.C. Efficacy of lacosamide in children and adolescents with drug-resistant epilepsy and refractory status epilepticus: A systematic review. Seizure, 2018, 56, 34-40.
[http://dx.doi.org/10.1016/j.seizure.2018.01.014] [PMID: 29428899]
[20]
Murgia, F.; Muroni, A.; Puligheddu, M.; Polizzi, L.; Barberini, L.; Orofino, G.; Solla, P.; Poddighe, S.; Del Carratore, F.; Griffin, J.L.; Atzori, L.; Marrosu, F. Metabolomics as a tool for the characterization of drug-resistant epilepsy. Front. Neurol., 2017, 8, 459.
[http://dx.doi.org/10.3389/fneur.2017.00459] [PMID: 28928712]
[21]
Al Zweiri, M.; Sills, G.J.; Leach, J.P.; Brodie, M.J.; Robertson, C.; Watson, D.G.; Parkinson, J.A. Response to drug treatment in newly diagnosed epilepsy: a pilot study of (1)H NMR- and MS-based metabonomic analysis. Epilepsy Res., 2010, 88(2-3), 189-195.
[http://dx.doi.org/10.1016/j.eplepsyres.2009.11.005] [PMID: 20005079]
[22]
Detour, J.; Bund, C.; Behr, C.; Cebula, H.; Cicek, E.A.; Valenti-Hirsch, M.P.; Lannes, B.; Lhermitte, B.; Nehlig, A.; Kehrli, P.; Proust, F.; Hirsch, E.; Namer, I.J. Metabolomic characterization of human hippocampus from drug-resistant epilepsy with mesial temporal seizure. Epilepsia, 2018, 59(3), 607-616.
[http://dx.doi.org/10.1111/epi.14000] [PMID: 29341105]
[23]
Fauvelle, F.; Boccard, J.; Cavarec, F.; Depaulis, A.; Deransart, C. Assessing susceptibility to epilepsy in three rat strains using brain metabolic profiling based on HRMAS NMR spectroscopy and chemometrics. J. Proteome Res., 2015, 14(5), 2177-2189.
[http://dx.doi.org/10.1021/pr501309b] [PMID: 25761974]
[24]
Boguszewicz, Ł.; Jamroz, E.; Ciszek, M.; Emich-Widera, E.; Kijonka, M.; Banasik, T.; Skorupa, A.; Sokół, M. NMR-based metabolomics in pediatric drug resistant epilepsy - preliminary results. Sci. Rep., 2019, 9(1), 15035.
[http://dx.doi.org/10.1038/s41598-019-51337-z] [PMID: 31636291]
[25]
Wei, C.; Li, Y.; Yao, H.; Liu, H.; Zhang, X.; Guo, R. A metabonomics study of epilepsy in patients using gas chromatography coupled with mass spectrometry. Mol. Biosyst., 2012, 8(8), 2197-2204.
[http://dx.doi.org/10.1039/c2mb25105a] [PMID: 22706165]
[26]
Moradi, P.; Ganjkhani, M.; Anarkooli, I.J.; Abdanipour, A. Neuroprotective effects of lovastatin in the pilocarpine rat model of epilepsy according to the expression of neurotrophic factors. Metab. Brain Dis., 2019, 34(4), 1061-1069.
[http://dx.doi.org/10.1007/s11011-019-00424-1] [PMID: 31144103]
[27]
Wang, S.H.; Cai, J.Z.; Sun, F.; Lin, Y.Y.; Liu, Z.Z.; Zhou, S.H.; Lin, Z.X.; Ma, J.S.; Wang, X.Q.; Wen, C.C. Serum metabolic changes in rats after intragastric administration of entinostat. Int. J. Clin. Exp. Med., 2016, 9, 3179-3184.
[28]
Wang, S.H.; Zhang, L.J.; Wang, X.Q.; Wang, Z.Y.; Wen, C.C.; Ma, J.S.; Gao, Z.M.; Hu, L.F. Metabolic changes in rat lung after acute paraquat poisoning by gas chromatography-mass spectrometry. Int. J. Clin. Exp. Med., 2016, 9, 21514-21520.
[29]
Wang, XC; Wang, ZY; Weng, J; Wen, CC; Chen, HL; Wang, XQ A new effective machine learning framework for sepsis diagnosis. IEEE Access, 2018, 6, 48300-48310.
[http://dx.doi.org/10.1109/ACCESS.2018.2867728]
[30]
Wang, X.; Zhang, M.; Ma, J.; Zhang, Y.; Hong, G.; Sun, F.; Lin, G.; Hu, L. Metabolic changes in paraquat poisoned patients and support vector machine model of discrimination. Biol. Pharm. Bull., 2015, 38(3), 470-475.
[http://dx.doi.org/10.1248/bpb.b14-00781] [PMID: 25757930]
[31]
Sun, J.H.; Jiang, Y.Y.; Zhuang, K.Z.; Yuan, Y.Q.; Wang, Y.P.; Yang, X.Z. Urine metabolomics after diazepam in rats by gas chromatography-mass spectrometry. Lat. Am. J. Pharm., 2018, 37, 1798-1801.
[32]
Deng, M.; Zhang, M.; Sun, F.; Ma, J.; Hu, L.; Yang, X.; Lin, G.; Wang, X. A gas chromatography-mass spectrometry based study on urine metabolomics in rats chronically poisoned with hydrogen sulfide. BioMed Res. Int., 2015, 2015, 295241.
[http://dx.doi.org/10.1155/2015/295241] [PMID: 25954748]
[33]
Zhang, Q.; Wu, H.; Wen, C.; Sun, F.; Yang, X.; Hu, L. Metabolic changes in rats after intragastric administration of MGCD0103 (Mocetinostat), a HDAC class I inhibitor. Int. J. Clin. Exp. Pathol., 2015, 8(8), 9320-9325.
[PMID: 26464683]
[34]
Wang, S.; Wu, H.; Geng, P.; Lin, Y.; Liu, Z.; Zhang, L.; Ma, J.; Zhou, Y.; Wang, X.; Wen, C. Pharmacokinetic study of dendrobine in rat plasma by ultra-performance liquid chromatography tandem mass spectrometry. Biomed. Chromatogr., 2016, 30(7), 1145-1149.
[http://dx.doi.org/10.1002/bmc.3641] [PMID: 26525040]
[35]
Wen, C.; Wang, S.; Huang, X.; Liu, Z.; Lin, Y.; Yang, S.; Ma, J.; Zhou, Y.; Wang, X. Determination and validation of hupehenine in rat plasma by UPLC-MS/MS and its application to pharmacokinetic study. Biomed. Chromatogr., 2015, 29(12), 1805-1810.
[http://dx.doi.org/10.1002/bmc.3499] [PMID: 26033449]
[36]
Wen, C.; Zhang, Q.; He, Y.; Deng, M.; Wang, X.; Ma, J. Gradient elution LC-MS determination of dasatinib in rat plasma and its pharmacokinetic study. Acta Chromatogr., 2015, 27, 81-91.
[http://dx.doi.org/10.1556/AChrom.27.2015.1.7]
[37]
Wang, X.; Wang, S.; Ma, J.; Ye, T.; Lu, M.; Fan, M.; Deng, M.; Hu, L.; Gao, Z. Pharmacokinetics in rats and tissue distribution in mouse of berberrubine by UPLC-MS/MS. J. Pharm. Biomed. Anal., 2015, 115, 368-374.
[http://dx.doi.org/10.1016/j.jpba.2015.07.031] [PMID: 26279368]
[38]
Wang, S.; Wu, H.; Huang, X.; Geng, P.; Wen, C.; Ma, J.; Zhou, Y.; Wang, X. Determination of N-methylcytisine in rat plasma by UPLC-MS/MS and its application to pharmacokinetic study. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2015, 990, 118-124.
[http://dx.doi.org/10.1016/j.jchromb.2015.03.025] [PMID: 25864013]
[39]
Wen, C.; Lin, F.; Huang, B.; Zhang, Z.; Wang, X.; Ma, J.; Lin, G.; Chen, H.; Hu, L. Metabolomics analysis in acute paraquat poisoning patients based on UPLC-Q-TOF-MS and machine learning approach. Chem. Res. Toxicol., 2019, 32(4), 629-637.
[http://dx.doi.org/10.1021/acs.chemrestox.8b00328] [PMID: 30807114]
[40]
Zhao, X.; Zhang, X.; Cai, Z.; Tian, X.; Wang, X.; Huang, Y.; Chen, H.; Hu, L. Chaos enhanced grey wolf optimization wrapped ELM for diagnosis of paraquat-poisoned patients. Comput. Biol. Chem., 2019, 78, 481-490.
[http://dx.doi.org/10.1016/j.compbiolchem.2018.11.017] [PMID: 30501982]
[41]
Hu, LF; Yang, PX; Wang, XQ; Lin, FY; Chen, HL; Cao, HC; Li, HY Using biochemical indexes to prognose paraquat-poisoned patients: an extreme learning machine-based approach. IEEE Access, 2019, 7, 42148-42155.
[42]
Zhang, Z.N.; Hu, L.M.; Wang, Q.Q.; Dong, Y.W.; Zhang, M.M.; Wang, X.Q.; Wang, S.H. Tissue metabolic changes in rats after administration of Aidi injection by GC-MS. Int. J. Clin. Exp. Med., 2019, 12, 3879-3887.
[43]
Li, L.Y.; Hu, L.M.; Chen, B.B.; Dong, Y.W.; Lin, Z.X.; Wang, Z.Y.; Wen, C.C.; Wang, X.Q.; Wang, S.H. Effect of activated carbon on methomyl poisoning by urine metabolomics base on gas chromatography-mass spectrometry. Acta Chromatogr., 2018, 30, 21-25.
[http://dx.doi.org/10.1556/1326.2017.00146]
[44]
Jiang, X.J.; Bao, X.; Ma, J.S.; Wen, C.C.; Wang, X.Q.; Ye, Y.Z. Effect of curcumin on acute paraquat poisoning by metabolomics. Curr. Pharm. Anal., 2018, 14, 635-643.
[http://dx.doi.org/10.2174/1573412914666180627142952]
[45]
Zhang, X.L.; Zeng, M.; Wu, B.; Sun, F.; Chen, L.G.; Wang, X.Q.; Wang, X.C. Identification of ketamine-addicted animal models based on radial basis function network. Lat. Am. J. Pharm., 2018, 37, 1168-1172.
[46]
Luo, X.H.; Zhang, J.; Zhang, Z.G.; Lin, Y.J.; Yu, Z.; Wang, X.Q.; Lin, K.Z. Urine metabolic changes of acute paraquat poisoning rats after intervention with curcumin. Lat. Am. J. Pharm., 2018, 37, 131-138.
[47]
Chen, L.G.; Tu, X.T.; Chen, B.B.; Zhang, J.; Ma, J.S.; Wang, X.Q. Effect of pirfenidone on rats with acute paraquat poisoning by urine metabolomics. Lat. Am. J. Pharm., 2018, 37, 420-424.
[48]
Chen, L.G.; Chen, D.X.; Wu, H.Y.; Zhuang, K.Z.; Chen, B.B.; Dong, Y.W.; Wen, C.C.; Wang, Z.Y.; Wang, X.Q.; Geng, P.W. GC/MS-Based metabolomic analysis of serum and urine in rats after dichlorvos poisoning. Lat. Am. J. Pharm., 2018, 37, 2057-2063.
[49]
Ma, J.; Sun, F.; Chen, B.; Tu, X.; Peng, X.; Wen, C.; Hu, L.; Wang, X. Tissue metabolic changes for effects of pirfenidone in rats of acute paraquat poisoning by GC-MS. Toxicol. Ind. Health, 2017, 33(12), 887-900.
[http://dx.doi.org/10.1177/0748233717731959] [PMID: 28978283]
[50]
Shen, Y.; Peng, W.; Chen, Q.; Hammock, B.D.; Liu, J.; Li, D.; Yang, J.; Ding, J.; Wang, X. Anti-inflammatory treatment with a soluble epoxide hydrolase inhibitor attenuates seizures and epilepsy-associated depression in the LiCl-pilocarpine post-status epilepticus rat model. Brain Behav. Immun., 2019, 81, 535-544.
[http://dx.doi.org/10.1016/j.bbi.2019.07.014] [PMID: 31306773]
[51]
Jia, R.; Jia, N.; Yang, F.; Liu, Z.; Li, R.; Jiang, Y.; Zhao, J.; Wang, L.; Zhang, S.; Zhang, Z.; Zhang, H.; Wu, S.; Gao, F.; Jiang, W. Hydrogen alleviates necroptosis and cognitive deficits in lithium-pilocarpine model of status epilepticus. Cell. Mol. Neurobiol., 2019, 39(6), 857-869.
[http://dx.doi.org/10.1007/s10571-019-00685-5] [PMID: 31089833]
[52]
Colciaghi, F.; Nobili, P.; Cipelletti, B.; Cagnoli, C.; Zambon, S.; Locatelli, D.; de Curtis, M.; Battaglia, G.S. Targeting PSD95-nNOS interaction by Tat-N-dimer peptide during status epilepticus is neuroprotective in MAM-pilocarpine rat model. Neuropharmacology, 2019, 153, 82-97.
[http://dx.doi.org/10.1016/j.neuropharm.2019.04.028] [PMID: 31047919]
[53]
Gimenes, A.D.; Andrade, B.F.D.; Pinotti, J.V.P.; Oliani, S.M.; Galvis-Alonso, O.Y.; Gil, C.D. Annexin A1-derived peptide Ac2-26 in a pilocarpine-induced status epilepticus model: antiinflammatory and neuroprotective effects. J. Neuroinflammation, 2019, 16(1)32
[http://dx.doi.org/10.1186/s12974-019-1414-7] [PMID: 30755225]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy