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The pro-convulsant effects of diazinon low dose in male rats under amygdala kindling
Fatemeh Saberi1, Farideh Bahrami2, Mehdi Saberi3,4
1Department of Dermatology, Razi Skin Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Abstract:
Organophosphates can damage the brain in systemic intoxication. In this study, the effects of a minimum toxic dose (MTD) of diazinon (DZ) on amygdala afterdischarge threshold (ADT), kindling acquisition and kindled seizure parameters were evaluated. Intact male rats were stereotactically implanted with a tripolar and two monopolar electrodes in the amygdala and dura respectively. After recovery, animals received daily either, olive oil (control), 15 or 30 mg/kg (MTD) of DZ intraperitoneally, and ADT, afterdischarge duration (ADD) at each stage (S1 to S5) of kindling and number of trials for kindling acquisition were determined daily. Also, the effect of DZ on stage 4 latency (S4L), ADD, stage 5 duration (S5D) and the activity of the red blood cholinesterase (ChE) were evaluated. The ADT was lower and the ADD was longer significantly in DZ treated group in comparison to control (p < 0.01) and the number of trials to reach each stage of kindling acquisition was reduced (p < 0.001). The total amount of ADDs during the kindling procedure increased significantly 5 days after DZ treatment. While the S4L was reduced, the S5D increased significantly after DZ treatment. The ChE activity was inhibited significantly after 20 min of DZ treatment and continued till 24 h (p < 0.01). Data indicate that even half of the MTD of DZ could increase the sensitivity and excitability of the CNS to the epileptic activity at least via reduction of stimulation threshold and AD prolongation. Furthermore, repeated exposure to the low concentrations of organophosphates may be pro-convulsant and should be restricted.
Insights
Organophosphates like diazinon (DZ) can lower brain seizure thresholds and prolong afterdischarge duration, increasing seizure susceptibility. Even low doses of DZ may act as a pro-convulsant, necessitating restricted exposure.
Area of Science:
- Neuroscience
- Toxicology
- Pharmacology
Background:
- Organophosphates are known neurotoxicants causing systemic intoxication.
- The central nervous system (CNS) effects of organophosphates, particularly their pro-convulsant potential, require further investigation.
Purpose of the Study:
- To evaluate the effects of a minimum toxic dose (MTD) of diazinon (DZ) on amygdala afterdischarge threshold (ADT), kindling acquisition, and seizure parameters in rats.
- To determine the impact of DZ on cholinesterase (ChE) activity.
Main Methods:
- Male rats were stereotactically implanted with electrodes in the amygdala.
- Animals received daily intraperitoneal injections of olive oil (control) or 15/30 mg/kg of DZ.
- ADT, afterdischarge duration (ADD), kindling acquisition rates, stage 4 latency (S4L), stage 5 duration (S5D), and red blood cell ChE activity were measured.
Main Results:
- DZ treatment significantly lowered ADT and prolonged ADD.
- Kindling acquisition was accelerated in DZ-treated rats, with reduced trials to reach each stage.
- S4L decreased, S5D increased, and ChE activity was significantly inhibited post-DZ administration.
Conclusions:
- Even sub-minimum toxic doses of DZ can enhance CNS excitability and sensitivity to epileptic activity.
- Organophosphates, even at low concentrations, may possess pro-convulsant properties and their exposure should be limited.
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