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Gas chromatography–mass spectrometry for metabolite profiling of Japanese medaka (Oryzias latipes) juveniles exposed to malathion

  • 15th International Symposium on Toxicity Assessment
  • Published:
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Abstract

Purpose

We evaluate malathion toxicity to Japanese medaka (Oryzias latipes) juveniles by using a mass spectrometry combined with gas chromatography (GC/MS) metabolomics approach.

Methods

Medaka were exposed to low (L) and high (H) concentrations (nominally 20 and 2,000 μg/L, respectively) of water-borne malathion. Metabolites were extracted from the fish, derivatized, and analyzed by GC/MS. Identified metabolites were subjected to one-way analysis of variance and principal component analysis (PCA). We examined the variations in the amounts of the metabolites during the exposure period.

Results and discussion

At 24 h, control, L, and H groups were separated along PC1, suggesting that the effects of malathion depended on exposure concentration. The PCA results at 96 h suggest that the metabolite profiles variations of the L and H groups differed, and thus that the effects of malathion in groups differed. At 24 h, the amounts of amino acids in both exposed groups were lower than the control group amounts, perhaps owing to accelerated protein synthesis. At 96 h, the amounts of almost all the amino acids increased in the L group but decreased in the H group relative to the control group amounts, suggesting the proteolysis occurred in the L group while protein synthesis continued in the H group, that the high malathion exposure affected the fish. In addition, at 96 h, gluconeogenesis may have been induced in the L group but not in H group.

Conclusions

Malathion exposure may have altered the balance between protein synthesis and degradation and induced gluconeogenesis in medaka. Our results suggest that metabolomics will be useful for comprehensive evaluation of toxicity.

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References

  • Abdollahi M, Donyavi M, Pournourmohammadi S, Saadat M (2004) Hyperglycemia associated with increased hepatic glycogen phosphorylase and phosphoenolpyruvate carboxykinase in rats following subchronic exposure to malathion. Comp Biochem Physiol C Toxicol Pharmacol 137:343–347. doi:10.1016/j.cca.2004.03.009

    Article  Google Scholar 

  • Aker WG, Hu X, Wang P, Hwang HM (2008) Comparing the relative toxicity of malathion and malaoxon in blue catfish Ictalurus furcatus. Environ Toxicol 23:548–554. doi:10.1002/tox.20371

    Article  CAS  Google Scholar 

  • Areechon N, Plumb JA (1990) Sublethal effects of malathion on channel catfish, Ictalurus punctatus. Bull Environ Contam Toxicol 44:435–442. doi:10.1007/BF01701226

    Article  CAS  Google Scholar 

  • Bonilla E, Hernández F, Cortés L, Mendoza M, Mejia J, Carrillo E, Casas E, Betancourt M (2008) Effects of the insecticides malathion and diazinon on the early oogenesis in mice in vitro. Environ Toxicol 23:240–245. doi:10.1002/tox.20332

    Article  CAS  Google Scholar 

  • Brewer SK, Little EE, DeLonay AJ, Beauvais SL, Jones SB, Ellersieck MR (2001) Behavioral dysfunctions correlate to altered physiology in rainbow trout (Oncorynchus mykiss) exposed to cholinesterase-inhibiting chemicals. Arch Environ Contam Toxicl 40:70–76. doi:10.1007/s002440010149

    Article  CAS  Google Scholar 

  • Chan ECY, Koh PK, Mal M, Cheah PY, Eu KW, Backshall A, Cavill R, Nicholson JK, Keun HC (2009) Metabolic profiling of human colorectal cancer using high-resolution magic angle spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy and gas chromatography mass spectrometry (GC/MS). J Proteome Res 8:352–361. doi:10.1021/pr8006232

    Article  CAS  Google Scholar 

  • Chatterjee S, Das SK, Chakravarty R, Chakrabarti A, Ghosh S, Guha AK (2009) Interaction of malathion, an organophosphorus pesticide with Rhizopus oryzae biomass. J Hazard Mater 174:47–53. doi:10.1016

    Article  Google Scholar 

  • Chorell E, Moritz T, Branth S, Antti H, Svensson MB (2009) Predictive metabolomics evaluation of nutrition-modulated metabolic stress responses in human blood serum during the early recovery phase of strenuous physical exercise. J Proteome Res 8:2966–2977. doi:10.1021/pr900081q

    Article  CAS  Google Scholar 

  • Dutta HM, Adhikari S, Singh NK, Roy PK, Munshi JS (1993) Histopathological changes induced by malathion in the liver of a freshwater catfish, Heteropneustes fossilis (Bloch). Bull Environ Contam Toxicol 51:895–900. doi:10.1007/BF00198287

    Article  CAS  Google Scholar 

  • Ekman DR, Teng Q, Jensen KM, Matinovic DL, Ankley GT, Collette TW (2007) NMR analysis of male fathead minnow urinary metabolites: a potential approach for studying impacts of chemical exposures. Aquat Toxicol 85:104–112. doi:10.1016/j.aquatox.2007.08.005

    Article  CAS  Google Scholar 

  • Galloway T, Handy R (2003) Immunotoxicity of organophosphorous pesticides. Ecotoxicology 12:345–363. doi:10.1023/A:1022579416322

    Article  CAS  Google Scholar 

  • González PF, Llanos-Rivera A, Baeza NC, Pérez EU (2011) Xenobiotic-induced changes in the arginase activity of zebrafish (Danio rerio) eleutheroembryo. Environ Toxicol Chem 30:2285–2291. doi:10.1002/etc.623

    Article  Google Scholar 

  • Goodacre R, Vaidyanathan S, Dunn WB, Harrigan GG, Kell DB (2004) Metabolomics by numbers: acquiring and understanding global metabolite data. Trends Biotechnol 22:245–252. doi:10.1016/j.tibtech.2004.03.007

    Article  CAS  Google Scholar 

  • Guimarães ATB, Silva de Assis HC, Boeger W (2007) The effect of trichlorfon on acetylcholinesterase activity and histopathology of cultivated fish Oreochromis niloticus. Ecotoxicol Environ Saf 68:57–62. doi:10.1016/j.ecoenv.2006.08.005

    Article  Google Scholar 

  • Huang X, Li S, Gong Y, Mao Y, Liu C, Qu H, Cheng Y (2008) A metabonomic characterization of CCl4-induced acute liver failure using partial least square regression based on the GC/MS metabolic profiles of plasma in mice. J Chromatogr B 870:178–185. doi:10.1016/j.jchromb.2008.05.049

    Article  CAS  Google Scholar 

  • Huculeci R, Dinu D, Staicu AC, Munteanu MC, Costache M, Dinischiotu A (2009) Malathion-induced alteration of the antioxidant defence system in kidney, gill, and intestine of Carassius auratus gibelio. Environ Toxicol 24:523–530. doi:10.1002/tox.20454

    Article  CAS  Google Scholar 

  • Joshi AKR, Rajini PSR (2009) Reversible hyperglycemia in rats following acute exposure to acephate, an organophosphorus insecticide: role of gluconeogenesis. Toxicology 257:40–45. doi:10.1016/j.tox.2008.12.006

    Article  CAS  Google Scholar 

  • Kavitha P, Rao JV (2008) Toxic effects of chlorpyrifos on antioxidant enzymes and target enzyme acetylcholinesterase interaction in mosquito fish, Gambusia affinis. Environ Toxicol Pharmacol 26:192–198. doi:10.1016/j.etap. 2008.03.010

    Article  CAS  Google Scholar 

  • Kimberly RH, Amber H, Cheolhwan O, Xiang Z, Jiri A, Maria SS (2008) Development of GC×GC/TOF-MS metabolomics for use in ecotoxicological studies with invertebrates. Aquat Toxicol 88:48–52. doi:10.1016/j.aquatox.2008.03.002

    Article  Google Scholar 

  • Kind T, Tolstikov V, Fiehn O, Weiss RH (2007) A comprehensive urinary metabolomic approach for identifying kidney cancer. Anal Biochem 363:185–195. doi:10.1016/j.ab.2007.01.028

    Article  CAS  Google Scholar 

  • Kokushi E, Uno S, Harada T, Koyama J (2012) 1H NMR-based metabolomics approach to assess toxicity of bunker a heavy oil to freshwater carp, Cyprinus carpio. Environ Toxicol. doi: 10.1002/tox.20653

  • Kumar R, Nagpure NS, Kushwaha B, Srivastava SK, Lakra WS (2010) Investigation of the genotoxicity of malathion to freshwater teleost fish Channa punctatus (Bloch) using the micronucleus test and comet assay. Arch Environ Contam Toxicol 58:123–130. doi:10.1007/s00244-009-9354-3

    Article  CAS  Google Scholar 

  • Lu W, Bennett BD, Rabinowitz JD (2008) Analytical strategies for LC-MS-based targeted metabolomics. J Chromatogr B 871:236–242. doi:10.1016/j.jchromb.2008.04.031

    Article  CAS  Google Scholar 

  • Luo B, Groenke K, Takors R, Wandrey C, Oldiges M (2007) Simultaneous determination of multiple intracellular metabolites in glycolysis, pentose phosphate pathway and tricarboxylic acid cycle by liquid chromatography–mass spectrometry. J Chromatogr A 1147:153–164. doi:10.1016/j.chroma.2007.02.034

    Article  CAS  Google Scholar 

  • Madsen R, Lundstedt T, Trygg J (2010) Chemometrics in metabolomics—a review in human disease diagnosis. Anal Chim Acta 659:23–33. doi:10.1016/j.aca.2009.11.042

    Article  CAS  Google Scholar 

  • McCarthy ID, Fuiman LA (2008) Growth and protein metabolism in red drum (Sciaenops ocellatus) larvae exposed to environmental levels of atrazine and malathion. Aquat Toxicol 88:220–229. doi:10.1016/j.aquatox.2008.05.001

    Article  CAS  Google Scholar 

  • Michell AW, Mosedale D, Grainger DJ, Barker RA (2008) Metabolomic analysis of urine and serum in Parkinson’s disease. Metabolomics 4:191–201. doi:10.1007/s11306-008-0111-9

    Article  CAS  Google Scholar 

  • Moore PD, Patlolla AK, Tchounwou PB (2011) Cytogenetic evaluation of malathion-induced toxicity in Sprague–Dawley rats. Mutat Res 725:78–82. doi:10.1016/j.mrgentox.2011.07.007

    Article  CAS  Google Scholar 

  • Moraes EP, Rupérez FJ, Plaza M, Herrero M, Barbas C (2011) Metabolomic assessment with CE-MS of the nutraceutical effect of Cystoseira spp extracts in an animal model. Electrophoresis 35:2055–2062. doi:10.1002/elps.201000546

    Article  Google Scholar 

  • Pasikanti KK, Norasmara J, Cai S, Mahendran R, Esuvaranathan K, Ho PC, Chan ECY (2010) Metabolic footprinting of tumorigenic and nontumorigenic uroepithelial cells using two-dimensional gas chromatography time-of-flight mass spectrometry. Anal Bioanal Chem 398:1285–1293. doi:10.1007/s00216-010-4055-3

    Article  CAS  Google Scholar 

  • Rahimi R, Abdollahi M (2007) A review on the mechanisms involved in hyperglycemia induced by organophosphorus pesticides. Pestic Biochem Physiol 88:115–121. doi:10.1016/j.pestbp.2006.10.003

    Article  CAS  Google Scholar 

  • Sahib IK, Prasada RKS, Sambasiva RKR, Ramana RKV (1984a) Sublethal toxicity of malathion on the proteases and free amino acid composition in the liver of the teleost, Tilapia mossambica (Peters). Toxicol Lett 20:59–62. doi:10.1016/0378-4274(84)90183-8

    Article  CAS  Google Scholar 

  • Sahib IK, Rao KR, Rao KV (1984b) Effect of malathion on protein synthetic potentiality of the tissues of the teleost, Tilapia mossambica (Peters), as measured through incorporation of [14C]amino acids. Toxicol Lett 20:63–67. doi:10.1016/0378-4274(84)90184-X

    Article  CAS  Google Scholar 

  • Sancho E, Ferrando MD, Fernandez C, Andreu E (1998) Liver energy metabolism of Anguilla anguilla after exposure to fenitrothion. Ecotoxicol Environ Saf 41:168–175. doi:10.1006/eesa.1998.1689

    Article  CAS  Google Scholar 

  • Saravanan M, Prabhu Kumar K, Ramesh M (2011) Haematological and biochemical responses of freshwater teleost fish Cyprinus carpio (Actinopterygii: Cypriniformes) during acute and chronic sublethal exposure to lindane. Pestic Biochem Physiol 100:206–211. doi:10.1016/j.pestbp. 2011.04.002

    Article  CAS  Google Scholar 

  • Sheffield SR, Lochmiller RL (2001) Effects of field exposure to diazinon on small mammals inhabiting a semienclosed prairie grassland ecosystem I. Ecological and reproductive effects. Environ Toxicol Chem 20:284–286. doi:10.1002/etc.5620200209

    Article  CAS  Google Scholar 

  • Sweilum MA (2006) Effect of sublethal toxicity of some pesticides on growth parameters, hematological properties and total production of Nile tilapia (Oreochromis niloticus L.) and water quality of ponds. Aquat Res 37:1079–1089. doi:10.1111/j.1365-2109.2006.01531.x

    Article  CAS  Google Scholar 

  • Vallejo M, García A, Tuñón J, García-Martínez D, Angulo S, Martin-Ventura JL, Blanco-Colio LM, Almeida P, Egido J, Barbas C (2009) Plasma fingerprinting with GC-MS in acute coronary syndrome. Anal Bioanal Chem 394:1517–1524. doi:10.1007/s00216-009-2610-6

    Article  CAS  Google Scholar 

  • Van Scoy AR, Lin YL, Anderson BS, Philips BM, Martin MJ, McCall J, Todd CR, Crane D, Sowby ML, Viant MR, Ronald ST, Tjeerdema RS (2010) Metabolic responses produced by crude versus dispersed oil in Chinook salmon pre-smolts via NMR-based metabolomics. Ecotoxicol Environ Saf 73:710–717. doi:10.1016/j.ecoenv.2010.03.001

    Article  Google Scholar 

  • Venkataramana GV, Rani PN, Murthy PS (2006) Impact of malathion on the biochemical parameters of gobiid fish, Glossogobius giuris (Ham). J Environ Biol 27:119–122

    CAS  Google Scholar 

  • Viant MR, Pincetich CA, Tjeerdema RS (2006) Metabolic effects of dinoseb, diazinon and esfenvalerate in eyed eggs and alevins of Chinook salmon (Oncorhynchus tshawytscha) determined by 1H NMR metabolomics. Aquat Toxicol 77:359–371. doi:10.1016/j.aquatox.2006.01.009

    Article  CAS  Google Scholar 

  • Voicu VA, Thiermann H, Rădulescu FS, Mircioiu C, Miron DS (2009) The toxicokinetics and toxicodynamics of organophosphonates versus the pharmacokinetics and pharmacodynamics of oxime antidotes: biological consequences. Basic Clin Pharmacol Toxicol 106:73–85. doi:10.1111/j.1742-7843.2009.00486.x

    Article  Google Scholar 

  • Wishart DS (2005) Metabolomics: the principles and potential applications to transplantation. Am J Transplant 5:2814–2820. doi:10.1111/j.1600-6143.2005.01119.x

    Article  CAS  Google Scholar 

  • Xu F, Zou L, Ong CN (2010) Experiment-originated variations, and multi-peak and multi-origination phenomena in derivatization-based GC-MS metabolomics. Trends Analyt Chem 29:269–280. doi:10.1016/j.trac.2009.12.007

    Article  CAS  Google Scholar 

  • Yang M, Zhang J, Zhu KY, Xuan T, Liu X, Guo Y, Ma E (2008) Increased activity and reduced sensitivity of acetylcholinesterase associated with malathion resistance in a field population of the oriental migratory locust, Locusta migratoria manilensis (Meyen). Pestic Biochem Physiol 91:32–38. doi:10.1016/j.pestbp. 2007.12.004

    Article  CAS  Google Scholar 

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Acknowledgment

This research was supported by the Environment Research and Technology Development Fund (RF-0909) of the Ministry of the Environment, Japan.

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Authors and Affiliations

  1. Education and Research Center for Marine Resources and Environment, Faculty of Fisheries, Kagoshima University, 50-20 Shimoarata 4-Chome, Kagoshima, 890-0056, Japan

    Seiichi Uno, Aoi Shintoyo, Emiko Kokushi, Masataka Yamamoto & Jiro Koyama

  2. Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama, 790-8577, Japan

    Kei Nakayama

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  1. Seiichi Uno
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  2. Aoi Shintoyo
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  3. Emiko Kokushi
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Correspondence to Seiichi Uno.

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Uno, S., Shintoyo, A., Kokushi, E. et al. Gas chromatography–mass spectrometry for metabolite profiling of Japanese medaka (Oryzias latipes) juveniles exposed to malathion. Environ Sci Pollut Res 19, 2595–2605 (2012). https://doi.org/10.1007/s11356-012-0834-z

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