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.

Antidiabetic activity and toxicity of Zizyphus spina-christi leaves.

The effect of the butanol extract of Zizyphus spina-christi (L.), Willd (Rhamnaceae) leaves and its major saponin glycoside, christinin-A, on the serum glucose and insulin levels was studied in non-diabetic control, type-I (insulin-dependent) and type-II (non-insulin-dependent) diabetic rats. Pretreatment either with 100 mg/kg butanol extract or christinin-A potentiated glucose-induced insulin release in non-diabetic control rats. In type-II but not in type-I diabetic rats pretreatment with the butanol extract or christinin-A improved the oral glucose tolerance and potentiated glucose-induced insulin release. Treatment either with 100 mg/kg butanol extract or christinin-A reduced the serum glucose level and increased the serum insulin level of non-diabetic control and type-II diabetic rats but not of type-I diabetic rats. Effects of the butanol extract and christinin-A were similar. Pretreatment of non-diabetic control and type-II diabetic rats either with 100 mg/kg butanol extract or christinin-A enhanced the glucose lowering and insulinotropic effects of 5 g/kg glibenclamide. The hyperglycemic and hypoinsulinemic effects of 30 mg/kg diazoxide in non-diabetic control and type-II diabetic rats were inhibited and antagonized, respectively by pretreatment with the butanol extract or christinin-A. The relaxant effects of different concentrations of diazoxide on the isolated norepinephrine-contracted aortic strips were inhibited by 100 micromol/l christinin-A or 10 micromol/l glibenclamide. The combination of glibenclamide and christinin-A led to complete inhibition of the relaxant effects of different concentrations of diazoxide. At a dose level much higher than that required to produce satisfactory insulinotropic and hypoglycemic effects, the butanol extract of Zizyphus spina-christi leaves produced a depressant effect on the central nervous system in rats. Treatment of rats with 100mg/kg butanol extract for 3 months produced no functional or structural disturbances in liver and kidney and no haematological changes. In addition, the oral LD50 of the butanol extract in mice was 3820 mg/kg, while that of glibenclamide was 3160 mg/kg. Thus, Zizyphusspina-christi leaves appears to be a safe alternative to lower blood glucose. The safe insulinotropic and subsequent hypoglycemic effects of Zizyphus spina-christi leaves may be due to a sulfonylurea-like activity.