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Biochemical characterization of dichlorvos-induced delayed neurotoxicity in rat
1Department of Biochemistry, Postgraduate Institute of Medical Education & Research, Chandigarh, India.
Abstract:
In vitro and in vivo studies were carried out to assess the delayed neurotoxicity potential of dichlorvos. In vitro, dichlorvos caused a concentration and time-dependent decrease in the activity of neuropathy target esterase (NTE). The Ki of dichlorvos for NTE was calculated to be 1.28 x 10(3) M-1 min-1. In vitro reactivation and ageing studies revealed that dichlorvos-inhibited NTE became refractory to activation by potassium fluoride after 5 min in the ageing medium, thus indicating the formation of an aged complex between dichlorvos and NTE. In vivo also, dichlorvos (200 mg/kg body wt) given as a single subcutaneous dose inhibited NTE in brain at various intervals after exposure (24 h, 10 days, and 21 days). The delayed neurotoxicity potential of dichlorvos was finally confirmed by the rota rod test, which revealed severe motor deficit in all the exposed animals.
Insights
Dichlorvos exposure significantly inhibits neuropathy target esterase (NTE) activity in vitro and in vivo. This inhibition, confirmed by motor deficit in animal studies, indicates dichlorvos
Area of Science:
- Toxicology
- Neuroscience
- Biochemistry
Background:
- Organophosphate pesticides like dichlorvos are widely used.
- Delayed neurotoxicity is a serious concern associated with some organophosphates.
- Neuropathy target esterase (NTE) is a key enzyme implicated in organophosphate-induced neurotoxicity.
Purpose of the Study:
- To investigate the in vitro and in vivo delayed neurotoxicity potential of dichlorvos.
- To assess the effect of dichlorvos on Neuropathy Target Esterase (NTE) activity.
- To confirm the neurotoxic effects of dichlorvos through behavioral testing.
Main Methods:
- In vitro enzyme inhibition assays to determine dichlorvos' effect on NTE activity and kinetics.
- In vitro reactivation and aging studies to characterize the dichlorvos-NTE interaction.
- In vivo administration of dichlorvos to rodents followed by NTE activity assessment in brain tissue.
- Rota rod tests to evaluate motor function in dichlorvos-exposed animals.
Main Results:
- Dichlorvos demonstrated a concentration- and time-dependent inhibition of NTE activity in vitro.
- The inhibition constant (Ki) for dichlorvos and NTE was determined to be 1.28 x 10(3) M-1 min-1.
- In vivo studies showed significant NTE inhibition in the brain following a single subcutaneous dose of dichlorvos.
- Aged complex formation between dichlorvos and NTE was observed, indicating irreversible inhibition.
- Exposed animals exhibited severe motor deficits in rota rod tests, confirming delayed neurotoxicity.
Conclusions:
- Dichlorvos possesses significant delayed neurotoxicity potential.
- Inhibition and subsequent aging of NTE by dichlorvos are key mechanisms underlying its neurotoxic effects.
- These findings highlight the risks associated with dichlorvos exposure and the importance of monitoring NTE activity.