Alpha-lipoic acid protects against potassium cyanide-induced seizures and mortality

This study was proposed to investigate the potential protective effect of alpha-lipoic acid (α-LA) against potassium cyanide (KCN)-induced seizures and lethality in mice. The intraperitoneal ED50 value of KCN, as measured by induction of clonic and tonic seizures was increased by pretreatment of mice with α-LA (25, 50 and 100 mg/kg) intraperitoneally in a dose-dependent manner. Similarly, the intraperitoneal LD50 value of KCN, based on 24 h mortality, was increased by pretreatment with α-LA in a dose-dependent manner. Intraperitoneal injection of the estimated ED50 of KCN (4.8 mg/kg) into mice increased, 1 h later, nitric oxide (NO) production and brain glutamate and malondialdehyde (MDA) levels. The estimated ED50 of KCN also decreased brain intracellular reduced glutathione (GSH) level and glutathione peroxidase (GSH-Px) activity in these animals. Administration of the estimated LD50 of KCN (6 mg/kg) produced, 24 h later, similar marked biochemical alterations in surviving animals. Pretreatment of mice with α-LA inhibited; dose-dependently KCN (ED50 and LD50)-induced an increase in NO production and brain MDA level as well as a decrease in brain intracellular GSH level and GSH-Px activity. The elevation induced by KCN in brain glutamate level was not inhibited by α-LA. It can be concluded that the protective effect of α-LA against KCN-induced seizures and lethality may be due to inhibition of NO overproduction and maintenance of intracellular antioxidant defense mechanisms.