Phenobarbital protection of cerebral NADPH-dependent lipid peroxidation: Possible involvement of a cytosolic glutathione-dependent system

Single (12 h, 24 h, 36 h and 48 h) and repeated (for 10 consecutive days) phenobarbital treatment (75 mg/kg) causes a characteristic alteration in NADPH-induced lipid peroxidation of rat brain tissue. The NADPH-induced lipid peroxidation is significantly inhibited in homogenate as well as in the 18,000 x g supernatant fraction while a significant increase is observed in microsomal preparation after phenobarbital treatment. Cytosolic fraction (105,000 x g supernatant) reversed the microsomal lipid peroxidation and this cytosolic protection is more marked in phenobarbital treated animals. Dialyzing or preheating the cytosol for 10 minutes at 60°C destroys its protective ability. However, glutathione (GSH, 2mM) supplementation of dialyzed cytosol restored this characteristic, while GSH alone or GSH supplemented heated cytosol failed to demonstrate this effect. These results indicate that the stimulation of barbiturate induced protection of cerebral NADPH-induced lipid peroxidation is mediated through a heat labile cytosolic GSH dependent system.