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The relationship between the bioactivation and detoxification of diazinon and chlorpyrifos, and the inhibition of acetylcholinesterase activity in Chirostoma jordani from three lakes with low to high organophosphate pesticides contamination

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Abstract

In fish, a number of studies have linked acetylcholinesterase (AChE) inhibition with exposure to organophosphate pesticides (OPs); however, evidence suggests the need to study aspects related to the bioactivation and detoxification of OPs, since their neurotoxicity is dependent on these processes. Thus, the study aim was to examine the relations between chlorpyrifos (CPF) and diazinon (DZN) bioactivation by hepatic CYP450 izoenzymes (CYP 2B6, CYP 2C19, CYP 3A4) and detoxification by aryl esterases and oxonases with brain and muscle AChE activity in Chirostoma jordani from three lakes with low to high OPs contamination in water and sediments. We found two patterns of bioactivation in vitro: (i) in fish from a lake with high CPF pollution, the main isoenzymes involved in this process were CYP 2C19>CYP 2B6>CYP 3A4, and (ii) in fish captured in a lake with a high concentration of DZN, the isoenzymes were CYP 3A4>CYP 2C19>CYP 2B6. Bioactivation is shown in this study to be fundamental in brain and muscle AChE inhibition in vivo. The rate of bioactivation of CPF was lower than for DZN. CPF bioactivation was accompanied by reduced detoxification and higher neurotoxicity, which was inversely dependent on the environmental contamination of CPF. Detoxification was also inversely correlated with environmental contamination by CPF, and was higher with diazoxon than chlorpyrifos-oxon. Oxonases were the most relevant enzymes involved in detoxification. The current findings suggest a series of strategies between the bioactivation and detoxification of OPs that allowed the survival of C. jordani despite of OPs pollution levels.

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Abbreviations

AChE:

Acetylcholinesterase

CPF:

Chlorpyrifos

CPO:

Chlorpyrifos-oxon

P450:

Cytochrome P450

CYP 2B6:

Isoform 2B6 of cytochrome P450

CYP 2C19:

Isoform 2C19 of cytochrome P450

CYP 3A4:

Isoform 3A4 of cytochrome P450

DZN:

Diazinon

DZO:

Diazoxon

MEC:

Molar extinction coefficient

OP:

Organophosphate pesticides

PCA:

Principal component analysis

References

  • Azimi-Gaylon S, Menconi M, Groger L, Karkoski J (2001) Diazinon and chlorpyrifos target analysis: workplan product for development of diazinon and chlorpyrifos total maximum daily loads in the Lower Sacramento River, Lower Feather River, Lower San Joaquin River, and the main channels of the Sacramento-San Joaquin River delta. Regional Water Quality Control Board, Central Valley Region Draft Report. pp 30

  • Bastos VL, Alves MV, Bernardino G, Ceccarelli PS, Bastos JC (2004) Paraoxonase activity in sera of four neotropical fish. Bull Environ Contam Toxicol 72(4):798–805

    CAS  Google Scholar 

  • Berger CW Jr, Sultatos LG (1997) The effects of the phosphorothioate insecticide fenitrothion on mammalian cytochrome P450-dependent metabolism of estradiol. Fund Appl Toxicol 37:150–157

    Article  CAS  Google Scholar 

  • Bradford M (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein–dye binding. Anal Biochem 72:248–254

    Article  CAS  Google Scholar 

  • Butler AM, Murray M (1997) Biotransformation of parathion in human liver: participation of CYP3A4 and its inactivation during microsomal parathion oxidation. J Pharmacol Exp Ther 280:966–973

    CAS  Google Scholar 

  • Carr LR, Chambers JE (1996) Kinetic analysis of in vitro inhibition, aging, and reactivation of brain acetylcholinesterase from rat and channel cat fish by paraoxon and chloropyrifos-oxon. Toxicol Appl Pharmacol 139:365–373

    Article  CAS  Google Scholar 

  • Chiba K, Kobayashi K, Manabe K, Tani M, Kamataki T, Ishizaki T (1993) Oxidative metabolism of omeprazole in human liver microsomes: cosegregation with S-mephenytoin 4’-hydroxylation. J Pharmacol Exp Ther 266:52–59

    CAS  Google Scholar 

  • Cole GM, Lim GP, Yang F, Teter B, Begum B, Harris-While ME, Frautschy SA (2005) Prevention of Alzheimer’s disease: omega-3 fatty acid and phenolic anti-oxidant interventions. Neurobiol Aging 26(1):133–136

    Article  Google Scholar 

  • Dzul-Caamal R, Domínguez-López ML, García-Latorre E, Vega-López A (2012) Implications of cytochrome 450 isoenzymes, aryl-esterase and oxonase activity in the inhibition of the acetylcholinesterase of Chirostoma jordani treated with phosphorothionate pesticides. Ecotox Environ Saf 84:199–206

    Article  CAS  Google Scholar 

  • Eaton D, Gilbert ST (2008) Principles of Toxicology. In: Klaassen CD (ed) Casarett and Doull′s Toxicology, the basic Science of Poisons, 7th edn. McGraw-Hill, New York, pp 11–44

    Google Scholar 

  • Environment Canada (2001) Canadian sediment/water/soil quality guidelines for the protection of aquatic life: summary tables. Updated. In Canadian environmental Quality guidelines, 1999, Canadian Council of Ministers of the Environment, Winnipeg

  • Galindo RJG, Fossato VU, Villagrana LC, Dolci F (1999) Pesticides in water, sediments and shrimp from a coastal lagoon off the Gulf of California. Mar Pollut Bull 38(9):837–841

    Article  Google Scholar 

  • Halpert J, Neal RA (1981) Cytochrome P-450-dependent metabolism of 1,1,2,2-tetrachloroethane to dichloroacetic acid in vitro. Biochem Pharmacol 30(11):1366–1368

    Article  CAS  Google Scholar 

  • Hao C, Nguyen B, Zhiao X, Chen E, Yang P (2010) Determination of residual carbamate, organophosphate, and phenyl urea pesticides in drinking and surface water by high-performance liquid chromatography/tandem mass spectrometry. J AOAC Int 93(2):400–410

    CAS  Google Scholar 

  • Hestrin S (1949) Reaction of the acetylcholine and other carboxylic acids derivates with hydroxylamine and its analytical application. J Biol Chem 180:249–261

    CAS  Google Scholar 

  • Islam S, Hossain MS, Nahar N, Mosihuzzaman M, Mamun MIR (2009) Application of high performance liquid chromatography to the analysis of pesticide residues in eggplants. J. Appl. Sci. 9:973–977

    Article  CAS  Google Scholar 

  • Kappers WA, Edwards RJ, Murray S, Boobis AR (2001) Diazinon is activated by CYP2C19 in human liver. Toxicol Appl Pharmacol 177:68–76

    Article  CAS  Google Scholar 

  • Keizer J, Dagostino G, Nagel R, Volpe T, Gnemi P, Vittozzi L (1995) Enzymological differences of Ache and diazinon hepatic-metabolism - correlation of in vitro data with the selective toxicity of diazinon to fish species. Sci Total Environ 171:213–220

    Article  CAS  Google Scholar 

  • Kirby MF, Morris S, Hurst M, Kirby SJ, Neall P, Taylor T, Fagg A (2000) The use of cholinesterase activity in flounder (Platichthys flesus) muscle tissue as a biomarker of neurotoxic contamination in UK estuaries. Mar Pollut Bull 40:780–791

    Article  CAS  Google Scholar 

  • Koenig S, Guillén K, Solé M (2013) Comparative xenobiotic metabolism capacities and pesticide sensitivity in adults of Solea solea and Solea senegalensis. Comp Biochem Physiol C 157(4):329–336

    CAS  Google Scholar 

  • Kousba AA, Sultatos LG, Poet TS, Timchalk C (2004) Comparison of chlorpyrifos-oxon and paraoxon acetylcholinesterase inhibition dynamics: potential role of a peripheral binding site. Toxicol Sci 80:239–248

    Article  CAS  Google Scholar 

  • Lewis DF (2005) Human P450s in the metabolism of drugs: molecular modelling of enzyme–substrate interactions. Expert Opin Drug Metab Toxicol 1(1):5–8

    Article  CAS  Google Scholar 

  • Montgomery J (1997) Agrochemicals desk reference, 2nd edn. CRC Press LLC, Boca Raton, p 656

    Book  Google Scholar 

  • Mutch E, Williams FM (2006) Diazinon, chlorpyrifos and parathion are metabolised by multiple cytochromes P450 in human liver. Toxicology 224:22–32

    Article  CAS  Google Scholar 

  • Na T, Fanf Z, Zhanqi G, Ming Z, Cheng S (2006) The status of pesticide residues in the drinking water sources in Meiliangwan Bay, Taihu Lake of China. Environ Monit Assess 123:351–370

    Article  CAS  Google Scholar 

  • Poet TS, Wu H, Kousba AA, Timchalk C (2003) In vitro rat hepatic and intestinal metabolism of the organophosphate pesticides chlorpyrifos and diazinon. Toxicol Sci 72:193–200

    Article  CAS  Google Scholar 

  • Ramírez J, Innocenti F, Schuetz EG, Flockhart DA, Relling MV, Santucci R, Ratain MJ (2004) CYP2B6, CYP3A4, AND CYP2C19 are responsible for the in vitro n-demethylation of meperidine in human liver microsomes. DMD 32:930–936

    Google Scholar 

  • Rawn DF, Quade SC, Shield JB, Conca G, Sun WF, Lacroix GM (2006) Organophosphate levels in apple composites and individual apples from a streated Canadian orchard. J Agric Food Chem 54:1943–1948

    Article  CAS  Google Scholar 

  • SAGARPA (2001) Norma Oficial Mexicana NOM-062-ZOO-1999 Especificaciones técnicas para la producción, cuidado y el uso de animales de laboratorio. Diario Oficial de la Federación. Segunda Sección, México, pp 1–57

    Google Scholar 

  • Sams C, Mason HJ, Rawbone R (2000) Evidence for the activation of organophosphate pesticides by cytochromes P450 3A4 and 2D6 in human liver microcosms. Toxicol Lett 116:217–221

    Article  CAS  Google Scholar 

  • SENER (2007) Anuario estadístico de la industria petroquímica. Secretaría de Energía, México, p 289

    Google Scholar 

  • Siepmann S, Finlayson B (2000) Water quality criteria for diazinon and chlorpyrifos. California Department of Fish and Game Report 00-3, p 59

  • Spacie A, McCathy LS, Rand GM (1995) Bioaccumulation and bioavailability in multiphase systems. In: Rand GM (ed) Fundamentals of aquatic toxicology, 2nd edn. Taylor & Francis, New York, pp 493–521

    Google Scholar 

  • Tang J, Cao Y, Rose RL, Brimfield AA, Dai D, Goldstein JA, Hodgson E (2001) Metabolism of chlorpyrifos by human cytochrome P450 isoforms and human, mouse and rat liver microsomes. Drug Metab Dispos 29:1201–1204

    CAS  Google Scholar 

  • USEPA (1998) Drinking water assessment of chlorpyrifos. In Pesticides and Toxic Substances. Washington, DC, US Environmental Protection Agency, Office of Prevention

  • USEPA (2005) Method 527. Determination of selected pesticides and flame retardants in drinking water by solid phase extraction and capillary column gas chromatography/mass spectrometry. United States Environmental Protection Agency. Cincinnati, Ohio. pp 44

  • Vega-López A, Carrillo-Morales CI, Olivares-Rubio HF, Domínguez-López ML, García-Latorre EA (2012) Evidence of bioactivation of halomethanes and its relation to oxidative stress response in Chirostoma riojai, an endangered fish from a polluted lake in Mexico. Arch Environ Toxicol 62(3):479–493

    Article  Google Scholar 

  • Vega-López A, Ayala-López G, Posadas-Espadas BP, Olivares-Rubio HF, Dzul-Caamal R (2013) Relations of oxidative stress in freshwater phytoplankton with heavy metals and polycyclic aromatic hydrocarbons. Comp Biochem Physiol A 165(4):498–507

    Article  Google Scholar 

  • Yang ZP, Dettbarn WD (1998) Prevention of tolerance to the organophosphorus anticholinesterase paraoxon with carboxylesterase inhibitors. Biochem Pharmacol 55:1419–1426

    Article  CAS  Google Scholar 

Download references

Acknowledgments

Acknowledgments —R. Dzul-Caamal is a CONACyT DSc student fellow. H.F. Olivares-Rubio is a CONACyT DSc student fellow. M.L. Domínguez-López, DSc; E. García-Latorre, PhD; and A. Vega-López, DSc, are fellows of Estímulos al Desempeño en Investigación, Comisión y Fomento de Actividades Académicas (IPN), and Sistema Nacional de Investigadores (SNI, CONACyT).

Funding

This study was financed by the Instituto Politécnico Nacional (IPN), SIP code 20101457, and CONACyT-ICyTDF, code 121184, Mexico.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standard

The procedures described in the present paper respect national and international safety regulations and ethical principles for animal welfare.

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Correspondence to Armando Vega-López.

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Dzul-Caamal, R., Domínguez-Lòpez, M.L., Olivares-Rubio, H.F. et al. The relationship between the bioactivation and detoxification of diazinon and chlorpyrifos, and the inhibition of acetylcholinesterase activity in Chirostoma jordani from three lakes with low to high organophosphate pesticides contamination. Ecotoxicology 23, 779–790 (2014). https://doi.org/10.1007/s10646-014-1216-8

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