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The Effect of Organophosphate Exposure on Neuronal Cell Coenzyme Q10 Status.
Neurochem Res. 2021 Jan; 46(1):131-139.NR

Abstract

Organophosphate (OP) compounds are widely used as pesticides and herbicides and exposure to these compounds has been associated with both chronic and acute forms of neurological dysfunction including cognitive impairment, neurophysiological problems and cerebral ataxia with evidence of mitochondrial impairment being associated with this toxicity. In view of the potential mitochondrial impairment, the present study aimed to investigate the effect of exposure to commonly used OPs, dichlorvos, methyl-parathion (parathion) and chloropyrifos (CPF) on the cellular level of the mitochondrial electron transport chain (ETC) electron carrier, coenzyme Q10 (CoQ10) in human neuroblastoma SH-SY5Y cells. The effect of a perturbation in CoQ10 status was also evaluated on mitochondrial function and cell viability. A significant decreased (P < 0.0001) in neuronal cell viability was observed following treatment with all three OPs (100 µM), with dichlorvos appearing to be the most toxic to cells and causing an 80% loss of viability. OP treatment also resulted in a significant diminution in cellular CoQ10 status, with levels of this isoprenoid being decreased by 72% (P < 0.0001), 62% (P < 0.0005) and 43% (P < 0.005) of control levels following treatment with dichlorvos, parathion and CPF (50 µM), respectively. OP exposure was also found to affect the activities of the mitochondrial enzymes, citrate synthase (CS) and mitochondrial electron transport chain (ETC) complex II+III. Dichlorvos and CPF (50 µM) treatment significantly decreased CS activity by 38% (P < 0.0001) and 35% (P < 0.0005), respectively compared to control levels in addition to causing a 54% and 57% (P < 0.0001) reduction in complex II+III activity, respectively. Interestingly, although CoQ10 supplementation (5 μM) was able to restore cellular CoQ10 status and CS activity to control levels following OP treatment, complex II+III activity was only restored to control levels in neuronal cells exposed to dichlorvos (50 µM). However, post supplementation with CoQ10, complex II+III activity significantly increased by 33% (P < 0.0005), 25% (P < 0.005) and 35% (P < 0.0001) in dichlorvos, parathion and CPF (100 µM) treated cells respectively compared to non-CoQ10 supplemented cells. In conclusion, the results of this study have indicated evidence of neuronal cell CoQ10 deficiency with associated mitochondrial dysfunction following OP exposure. Although CoQ10 supplementation was able to ameliorate OP induced deficiencies in CS activity, ETC complex II+III activity appeared partially refractory to this treatment. Accordingly, these results indicate the therapeutic potential of CoQ10 supplementation in the treatment of OP poisoning. However, higher doses may be required to engender therapeutic efficacy.

Authors+Show Affiliations

School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK.School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK.School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK.School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK.School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK.The Royal Liverpool University Hospital, Royal Liverpool and Broadgreen NHS Trust, Prescot Street, Liverpool, UK.School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK. i.p.hargreaves@ljmu.ac.uk.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32306167

Citation

Turton, Nadia, et al. "The Effect of Organophosphate Exposure On Neuronal Cell Coenzyme Q10 Status." Neurochemical Research, vol. 46, no. 1, 2021, pp. 131-139.
Turton N, Heaton RA, Ismail F, et al. The Effect of Organophosphate Exposure on Neuronal Cell Coenzyme Q10 Status. Neurochem Res. 2021;46(1):131-139.
Turton, N., Heaton, R. A., Ismail, F., Roberts, S., Nelder, S., Phillips, S., & Hargreaves, I. P. (2021). The Effect of Organophosphate Exposure on Neuronal Cell Coenzyme Q10 Status. Neurochemical Research, 46(1), 131-139. https://doi.org/10.1007/s11064-020-03033-y
Turton N, et al. The Effect of Organophosphate Exposure On Neuronal Cell Coenzyme Q10 Status. Neurochem Res. 2021;46(1):131-139. PubMed PMID: 32306167.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The Effect of Organophosphate Exposure on Neuronal Cell Coenzyme Q10 Status. AU - Turton,Nadia, AU - Heaton,Robert A, AU - Ismail,Fahima, AU - Roberts,Sioned, AU - Nelder,Sian, AU - Phillips,Sue, AU - Hargreaves,Iain P, Y1 - 2020/04/18/ PY - 2020/02/27/received PY - 2020/04/10/accepted PY - 2020/04/08/revised PY - 2020/4/20/pubmed PY - 2021/8/13/medline PY - 2020/4/20/entrez KW - Chloropyrifos KW - Coenzyme Q10 KW - Dichlorvos KW - Methyl-parathion KW - Mitochondria KW - Organophosphate SP - 131 EP - 139 JF - Neurochemical research JO - Neurochem Res VL - 46 IS - 1 N2 - Organophosphate (OP) compounds are widely used as pesticides and herbicides and exposure to these compounds has been associated with both chronic and acute forms of neurological dysfunction including cognitive impairment, neurophysiological problems and cerebral ataxia with evidence of mitochondrial impairment being associated with this toxicity. In view of the potential mitochondrial impairment, the present study aimed to investigate the effect of exposure to commonly used OPs, dichlorvos, methyl-parathion (parathion) and chloropyrifos (CPF) on the cellular level of the mitochondrial electron transport chain (ETC) electron carrier, coenzyme Q10 (CoQ10) in human neuroblastoma SH-SY5Y cells. The effect of a perturbation in CoQ10 status was also evaluated on mitochondrial function and cell viability. A significant decreased (P < 0.0001) in neuronal cell viability was observed following treatment with all three OPs (100 µM), with dichlorvos appearing to be the most toxic to cells and causing an 80% loss of viability. OP treatment also resulted in a significant diminution in cellular CoQ10 status, with levels of this isoprenoid being decreased by 72% (P < 0.0001), 62% (P < 0.0005) and 43% (P < 0.005) of control levels following treatment with dichlorvos, parathion and CPF (50 µM), respectively. OP exposure was also found to affect the activities of the mitochondrial enzymes, citrate synthase (CS) and mitochondrial electron transport chain (ETC) complex II+III. Dichlorvos and CPF (50 µM) treatment significantly decreased CS activity by 38% (P < 0.0001) and 35% (P < 0.0005), respectively compared to control levels in addition to causing a 54% and 57% (P < 0.0001) reduction in complex II+III activity, respectively. Interestingly, although CoQ10 supplementation (5 μM) was able to restore cellular CoQ10 status and CS activity to control levels following OP treatment, complex II+III activity was only restored to control levels in neuronal cells exposed to dichlorvos (50 µM). However, post supplementation with CoQ10, complex II+III activity significantly increased by 33% (P < 0.0005), 25% (P < 0.005) and 35% (P < 0.0001) in dichlorvos, parathion and CPF (100 µM) treated cells respectively compared to non-CoQ10 supplemented cells. In conclusion, the results of this study have indicated evidence of neuronal cell CoQ10 deficiency with associated mitochondrial dysfunction following OP exposure. Although CoQ10 supplementation was able to ameliorate OP induced deficiencies in CS activity, ETC complex II+III activity appeared partially refractory to this treatment. Accordingly, these results indicate the therapeutic potential of CoQ10 supplementation in the treatment of OP poisoning. However, higher doses may be required to engender therapeutic efficacy. SN - 1573-6903 UR - https://www.unboundmedicine.com/medline/citation/32306167/The_Effect_of_Organophosphate_Exposure_on_Neuronal_Cell_Coenzyme_Q10_Status_ L2 - https://doi.org/10.1007/s11064-020-03033-y DB - PRIME DP - Unbound Medicine ER -