Most effects of the peroxisome proliferator
clofibrate on rat liver are marginal or absent in
selenium (Se) deficiency. The purpose of the present study was to determine whether the uptake or distribution of
clofibrate 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 groups of rats received radiolabeled
clofibrate by intubation.
Clofibric acid was an ineffective as
clofibrate in producing effects (i.e. decreased
body weight gain, increases in liver somatic index and
protein content of the mitochondrial fraction, and increased activities of
catalase and peroxisomal
fatty acid beta-oxidation) in the liver of Se-deficient 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, liver and kidney) nor the urinary excretion of 14C was affected by Se deficiency. These results demonstrate that the hydrolysis of
clofibrate to
clofibric acid is not impaired in the Se-deficient rat. In addition, the involvement of Se in the effects of
peroxisome proliferators differs for different members of this structurally heterogeneous group of compounds. It is concluded that the Se-deficient rat may provide valuable information concerning the biochemical mechanism(s) underlying peroxisome proliferation.