FURTHER-STUDIES ON THE INVOLVEMENT OF SELENIUM IN PEROXISOME PROLIFERATION IN RAT-LIVER - COMPARISON OF EFFECTS WITH CLOFIBRIC ACID AND PERFLUOROOCTANOIC ACID AND THE PHARMACOKINETICS OF [C-14] CLOFIBRATE

Most effects of the peroxisome proliferator clofibrate on rat liver ar e marginal or absent in selenium (Se) deficiency. The purpose of the p resent study was to determine whether the uptake or distribution of cl ofibrate is altered by Se deficiency. Rats were fed a Se-adequate or - deficient diet for 10-11 weeks and then these same diets with 0.5% (w/ w) clofibric acid (the direct acting hydrolysis product of clofibrate) or 0.02% (w/w) perfluorooctanoic acid (PFOA) for 10 days. Other group s of rats received radiolabeled clofibrate by intubation. Clofibric ac id was as ineffective as clofibrate in producing effects (i.e. decreas ed body weight gain, increases in liver somatic index and protein cont ent of the mitochondrial fraction, and increased activities of catalas e and peroxisomal fatty acid beta-oxidation) in the liver of Se-defici ent rats. Microsomal omega-hydroxylation was, however, equally induced in both dietary groups. In contrast to clofibric acid, the biological effects of PFOA were not affected by Se status. Furthermore, neither the tissue distribution (plasma, fiver and kidney) nor the urinary exc retion of C-14 was affected by Se deficiency. These results demonstrat e that the hydrolysis of clofibrate to clofibric acid is not impaired in the Se-deficient rat. In addition, the involvement of Se in the eff ects of peroxisome proliferators differs for different members of this structurally heterogenous group of compounds. It is concluded that th e Se-deficient rat may provide valuable information concerning the bio chemical mechanism(s) underlying peroxisome proliferation.