Menthol Dissolved in Dimethyl Sulfoxide Protects Against Epileptiform Activity Induced by Pentylenetetrazol in Male Rats.

Introduction: This research aims to investigate the protective action of menthol dissolved in dimethyl sulfoxide (DMSO) on experimental epileptiform activity induced by the intraperitoneal (IP) injection of pentylenetetrazol (PTZ) in male rats.

Methods: Thirty adult male Wistar rats weighing 200-250 g were randomly assigned to five equal groups. The control animals received normal saline (200 μL) and the rest four cohorts were considered as treatment. Menthol was dissolved in DMSO and intraperitoneally injected at the doses of 100, 200, and 400 mg/kg into the first, second, and third groups (M100, M200, and M400 V=200 μL), respectively. The fourth treatment was injected with the solvent (200 μL). The animals were anesthetized, then underwent cranial surgery and a recording electrode was implanted in the stratum radiatum of the hippocampal carbonic anhydrase 1 (CA1) region (AP=-2.76 mm, ML=-1.4 mm and DV=3 mm). The seizure activity was induced by PTZ (IP) and assessed by counting and measuring amplitudes of the spikes for 10 minutes using the eTrace program.

Results: Menthol was observed to significantly reduce the activity level of PTZ-induced epileptiform activity, as well as exert a protective and inhibitory action on proconvulsant effect of DMSO in a dose-dependent manner.

Conclusion: Menthol can potentially be used as an adjuvant to prevent seizure activity.

Highlights: Dimethyl sulfoxide (DMSO) induces proconvulsant effects, significantly increasing spike counts.Menthol 100 mg/kg also stimulates seizure activity, leading to a substantial spike count increase.Menthol 200 and 400 mg/kg exhibit inhibitory effects, decreasing seizure activity and spike counts.

Plain Language Summary: In this study, we explored the potential protective effects of menthol, dissolved in dimethyl sulfoxide (DMSO), on experimentally induced epileptiform activity in male rats. Our research involved thirty adult male Wistar rats, divided into five groups. While the control group received normal saline, the remaining four groups were treated with different doses of menthol in DMSO. The rats underwent surgery, and electrodes were implanted in the hippocampal region for recording. Using pentylenetetrazol (PTZ) to induce seizure activity, we observed that menthol, administered at varying doses, significantly reduced the level of epileptiform activity triggered by PTZ. Notably, menthol also demonstrated a protective and inhibitory effect on the proconvulsant action of DMSO, and this effect was dose-dependent. In simpler terms, our findings suggest that menthol has the potential to be used as an additional treatment to prevent seizure activity. This means that incorporating menthol, especially at specific doses, may offer a protective influence against epileptic events. This research sheds light on a promising avenue for potential therapeutic interventions, emphasizing the importance of further exploration of menthol's role in epilepsy prevention. Ultimately, our study opens the door to considering menthol as a valuable component in the development of strategies to mitigate the impact of seizures.