Related Experiment Video
Updated: Jul 9, 2026
Pentylenetetrazole-Induced Kindling Mouse Model
Published on: June 12, 2018
Diphenyl diselenide-induced seizures in rat pups: possible interaction with glutamatergic system
Marina Prigol1, Ethel A Wilhelm, Eluza C Stangherlin
1Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, RS, Brazil.
Insights
Diphenyl diselenide and glutamate co-administration in rat pups primarily caused glutamate-induced neurotoxicity, not involving oxidative stress. NMDA receptors play a role in diphenyl diselenide seizures.
Area of Science:
- Neuroscience
- Toxicology
- Biochemistry
Background:
- The glutamatergic system is crucial for brain function, but its dysregulation can lead to seizures.
- Diphenyl diselenide is an organoselenium compound with potential neurotoxic effects.
- Understanding the interaction between diphenyl diselenide, glutamate, and oxidative stress in developing brains is important.
Purpose of the Study:
- To investigate the role of the glutamatergic system in diphenyl diselenide-induced seizures in rat pups.
- To evaluate the involvement of oxidative stress in seizures caused by diphenyl diselenide and glutamate.
- To elucidate the specific glutamate receptor subtypes involved.
Main Methods:
- Administration of diphenyl diselenide and/or glutamate to rat pups (postnatal days 12-14).
- Assessment of seizure latency, seizure episode frequency, and neurochemical markers (lipid peroxidation, enzyme activities, glutamate uptake).
- Pharmacological manipulation using N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists (MK-801 and DNQX).
Main Results:
- Concomitant administration of diphenyl diselenide and glutamate resulted in glutamate being the primary driver of neurotoxicity.
- Oxidative stress markers were not significantly altered in glutamate-induced seizures.
- NMDA receptor antagonism (MK-801) prolonged seizure latency, indicating NMDA receptor involvement in diphenyl diselenide seizures.
- DNQX did not protect against diphenyl diselenide-induced seizures, suggesting a limited role for non-NMDA receptors.
- Diphenyl diselenide, at a low dose, exhibited a protective effect against glutamate-induced seizures.
Conclusions:
- Glutamate is the main neurotoxic agent when co-administered with diphenyl diselenide in rat pups.
- Oxidative stress is not implicated in glutamate-induced seizures in this model.
- NMDA glutamatergic receptors are partially involved in diphenyl diselenide-induced seizures.
- Low-dose diphenyl diselenide may offer protection against glutamate-induced seizures.
Abstract:
The aims of the present study were to investigate the possible involvement of glutamatergic system in seizures induced by diphenyl diselenide in rat pups (postnatal day, 12-14) and to evaluate the role of oxidative stress in seizures induced by diphenyl diselenide/glutamate. Glutamate (4 g/kg of body weight) administered in association with diphenyl diselenide (500 mg/kg of body weight) increased the latency for the appearance of the first seizure episode, reduced lipid peroxidation levels and catalase, Na+,K+-ATPase and delta-ALA-D activities. At the lowest dose (5 mg/kg of body weight), diphenyl diselenide reduced the appearance of seizure episodes induced by glutamate but did not alter the latency for the onset of the first episode. Glutamate uptake was inhibited in glutamate, diphenyl diselenide (the highest dose) and in the association of diphenyl diselenide (both doses) and glutamate groups. Pre-treatment with a N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801 (5S,10R-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate), significantly prolonged the latency for the onset for the first convulsive episode. A non-NMDA receptor antagonist, DNQX (6,7-dinitroquinoxaline-2,3-dione), did not protect seizures induced by diphenyl diselenide. The results of the present study demonstrated that: (a) when diphenyl diselenide and glutamate were administered concomitantly in pups, glutamate was the main responsible for the neurotoxic effects; (b) oxidative stress was not involved in glutamate-induced seizures; (c) NMDA glutamatergic receptors, were at least in part, involved in diphenyl diselenide- induced seizures; and (d) diphenyl diselenide, at the lowest dose, protected seizures induced by glutamate.
Related Concept Videos
01:24Epilepsy and Seizures: Overview
Various factors can trigger epilepsy, including genetic factors, brain damage, metabolic causes, and unknown etiology. Diagnosis of epilepsy involves electroencephalography (EEG), which...
01:14Antiepileptic Drugs: Glutamate Antagonists