The Effect of Organophosphate Exposure on Neuronal Cell Coenzyme Q(10) Status

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 Q(10) (CoQ(10)) in human neuroblastoma SH-SY5Y cells. The effect of a perturbation in CoQ(10) 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 CoQ(10) 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 CoQ(10) supplementation (5 μM) was able to restore cellular CoQ(10) 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 CoQ(10), 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-CoQ(10) supplemented cells. In conclusion, the results of this study have indicated evidence of neuronal cell CoQ(10) deficiency with associated mitochondrial dysfunction following OP exposure. Although CoQ(10) 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 CoQ(10) supplementation in the treatment of OP poisoning. However, higher doses may be required to engender therapeutic efficacy.