Evaluating the Efficacy of Propofol Against Isoniazid-Induced Seizures: A Comparative Study with Diazepam and Pyridoxine in Swiss Albino Mice
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Objective
Acute isoniazid toxicity causes refractory seizures due to pyridoxine deficiency-mediated gamma-aminobutyric acid depletion. While pyridoxine is the established antidote, its limited availability in emergency settings necessitates alternative treatments. This study aimed to evaluate the anticonvulsant efficacy of propofol, a GABA A receptor agonist and N-methyl-D-aspartate receptor antagonist, compared to pyridoxine and diazepam in isoniazid-induced seizures in mice.
Methods
Thirty-two Swiss albino mice were pretreated with: (1) normal saline (10 mL/kg), (2) pyridoxine (300 mg/kg), (3) propofol (50 mg/kg), or (4) diazepam (2.5 mg/kg), followed by isoniazid (300 mg/kg) after 30 minutes. All drugs were administered intraperitoneally. Seizure latency, duration, time to death, and survival were monitored for 120 minutes. Outcomes were analyzed using Kaplan-Meier/log-rank tests and ANOVA with Tukey’s post-hoc test.
Results
Isoniazid induced seizures and 100% mortality in the control group. Pyridoxine did not prevent seizures or improve survival (8/8 seizures and deaths). Propofol failed to improve seizure frequency, latency, duration, mortality, or time to death (8/8 seizures and deaths). Diazepam significantly reduced seizure frequency and mortality to 1 of 8 mice (p < 0.001), and delayed seizure onset.
Conclusion
Pretreatment with either propofol or pyridoxine failed to protect against isoniazid-induced seizures and death in mice. In contrast, diazepam was effective in preventing both seizures and death. Further studies are needed to investigate different propofol administration protocols and alternative animal models.
