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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- 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
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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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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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DOI: https://doi.org/10.1007/s10646-014-1216-8


