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Role of nitric oxide on insulin induced seizures in mice
1Department of Pharmacology, PIGIMER, Chandigarh.
Abstract:
The role of nitric oxide (NO) on acute hypoglycemia-induced seizures in mice was investigated using insulin as the hypoglycemic agent. The NO precursor L-arginine in the doses of 150, 500 and 750 mg/kg exhibited a dose-dependent protective effect against seizures induced by 8 mu/kg insulin. The NO synthase inhibitor (L-NMMA) at the doses of 50 and 100 mg/kg potentiated the subconvulsive doses of insulin (2 mu/kg). The onset, duration, number of seizures and the mortality were noted in a 2 hr study period. The results of this study suggest than NO plays an important protective role in acute hypoglycemia induced seizures which are known to occur through the activation of NMDA receptors.
Insights
Nitric oxide (NO) protects against seizures caused by acute hypoglycemia. Boosting NO levels with L-arginine prevented seizures, while inhibiting NO synthesis with L-NMMA worsened them.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Acute hypoglycemia can trigger seizures, a serious neurological complication.
- Nitric oxide (NO) is a signaling molecule implicated in various brain functions.
- Understanding NO's role in hypoglycemia-induced seizures is crucial for potential therapeutic interventions.
Purpose of the Study:
- To investigate the role of nitric oxide (NO) in acute hypoglycemia-induced seizures.
- To determine the effects of NO modulation (precursor and inhibitor) on seizure activity.
Main Methods:
- Insulin was used to induce acute hypoglycemia and seizures in a mouse model.
- The NO precursor, L-arginine, was administered at varying doses (150, 500, 750 mg/kg).
- The NO synthase inhibitor, L-NMMA, was administered at varying doses (50, 100 mg/kg).
- Seizure onset, duration, number, and mortality were recorded over a 2-hour period.
Main Results:
- L-arginine demonstrated a dose-dependent protective effect against insulin-induced seizures.
- L-NMMA potentiated the seizure-inducing effects of subconvulsive insulin doses.
- NO modulation significantly impacted seizure parameters and mortality.
Conclusions:
- Nitric oxide (NO) plays a significant protective role in mitigating acute hypoglycemia-induced seizures.
- These findings suggest NO-based strategies could be beneficial for managing seizures associated with hypoglycemia.
- The mechanism may involve the modulation of NMDA receptor activity.