Effect of lipid peroxide loading on lipid peroxidation and on the glutathione and cytochrome systems in rabbits

New Zealand White rabbits (6 males and 6 females) were fed a diet of high lipid peroxide content (peroxide value: 249.05 meq/kg fat) for 21 days. Twelve rabbits served as controls (peroxide value: 40.3 meq/kg fat). The lipid peroxide loading did not cause clinical signs. The rate of lipid peroxidation, as measured on the basis of thiobarbituric acid reactive substances (TBARS), was significantly (P < 0.05) higher in all of the investigated tissues, in the following order: liver > red blood cells (RBC) > blood plasma. Reduced and oxidised glutathione content was higher in the blood plasma (P < 0.01) and liver (P < 0.001) of rabbits exposed to the peroxide load. Lipid peroxide loading decreased the activity of glutathione peroxidase in the blood plasma, RBC haemolysate and liver and that of glutathione reductase in the liver. The amount of cytochrome P450 (both CO- and metyrapone-reduced) and the activity of cytochrome c (P450) oxidoreductase in the microsomal fraction of the liver homogenate were also lower in the group exposed to lipid peroxide load. Subchronic alimentary lipid peroxide loading in the presence of sufficiently high levels of antioxidants in the complete feed was found to increase the rate of lipid peroxidation and markedly lower the activities of both the glutathione and xenobiotic transforming enzyme systems without causing any clinical signs of toxicity.