Serum paraoxonase activity and the extent of lipid peroxidation are not affected by increased levels of human apolipoprotein A-I: studies in transgenic mice.

The present study analyzed the effect of increased concentrations of human apolipoprotein (apo) A-I in transgenic mice serum on paraoxonase activity and on lipid peroxidation. In the transgenic mice serum, in comparison to control (non-transgenic) C57BL/6 mice, we found high concentrations of human apoA-I and high-density lipoprotein (HDL)-cholesterol, but serum lipid peroxidation (basal and free radical-induced) and serum paraoxonase activity were similar in the two mouse groups. Comparing the individual results, no significant correlation was found between free radical-induced serum lipid peroxidation and apoA-I concentrations. Serum paraoxonase activity also did not correlate with serum concentrations of human apoA-I. However, a significant inverse relationship (R2=0.75) was observed between the individual values of paraoxonase activity and free radical-induced lipid peroxidation in both mouse groups. Direct analysis of the effect of pure human apoA-I and paraoxonase (using the specific paraoxonase inhibitor PD-92770) on lipid peroxidation also revealed that paraoxonase, but not apoA-I, protects serum lipids from oxidation. We thus conclude that the increased human apoA-I concentration in the mouse serum neither affect serum paraoxonase activity, nor protects against lipid peroxidation, whereas paraoxonase significantly inhibits serum lipid peroxidation.