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 ED(50) 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 LD(50) value of KCN, based on 24h mortality, was increased by pretreatment with α-LA in a dose-dependent manner. Intraperitoneal injection of the estimated ED(50) of KCN (4.8 mg/kg) into mice increased, 1h later, nitric oxide (NO) production and brain glutamate and malondialdehyde (MDA) levels. The estimated ED(50) of KCN also decreased brain intracellular reduced glutathione (GSH) level and glutathione peroxidase (GSH-Px) activity in these animals. Administration of the estimated LD(50) of KCN (6 mg/kg) produced, 24h later, similar marked biochemical alterations in surviving animals. Pretreatment of mice with α-LA inhibited; dose-dependently KCN (ED(50) and LD(50))-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.
Abdel-Zaher
Ahmed O
AO
Department of Pharmacology, Faculty of Medicine, Assiut University, Assiut, Egypt. ahmedosmanaz@hotmail.com
Abdel-Hady
Randa H
RH
Abdel Moneim
Wafaa M
WM
Salim
Safa Y
SY
D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D007928:Lethal Dose 50; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D011190:Potassium Cyanide / Q000633:toxicity*; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*; D008063:Thioctic Acid / Q000627:therapeutic use*
D000975:Antioxidants; D009573:Nitrites; D009569:Nitric Oxide; D018698:Glutamic Acid; D008063:Thioctic Acid; D005979:Glutathione Peroxidase; D005978:Glutathione; D011190:Potassium Cyanide