Comparison of propofol, diazepam, and pyridoxine for isoniazid-induced seizures in Swiss albino mice

Introduction 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. Propofol is a gamma-aminobutyric acid type A receptor agonist and N-methyl-D-aspartate receptor antagonist and is a compelling candidate for isoniazid-induced seizures. We compared the anticonvulsant effect of propofol, pyridoxine, and diazepam in isoniazid-induced seizures in mice.Methods Thirty-two Swiss albino mice were pretreated with intraperitoneal doses of normal saline (control) (10 mL/kg), pyridoxine (300 mg/kg), propofol (50 mg/kg), or diazepam (2.5 mg/kg), followed by isoniazid (300 mg/kg) after 30 minutes. We monitored the mice for 120 minutes. We measured time to seizure, seizure duration, time to death, and survival rates. We analyzed data using one-way analysis of variance with Tukey's post-hoc test.Results Isoniazid rapidly induced seizures and 100% mortality in the control group. Diazepam significantly reduced seizure frequency and mortality to 1 of 8 mice (p < 0.001), and delayed seizure onset. Neither pyridoxine nor propofol prevented seizures or improved survival.Discussion The ineffectiveness of pyridoxine suggests a different mechanism of toxicity in mice than in humans. This pre-treatment model might not predict the effectiveness of drugs given after seizure onset. Rapid clearance of propofol and the 30 minutes interval to INH may have obscured a possible effect. Further studies should investigate propofol by intravenous infusion and should use animal models more similar to humans.Conclusion Pretreatment of mice with diazepam effectively prevented seizures and death from isoniazid poisoning. Neither propofol nor pyridoxine protected against isoniazid-induced seizures and death in mice.