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 [14C]clofibrate.
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.
Olsson
U
U
Department of Genetic and Cellular Toxicology, Wallenberg Laboratory, Stockholm University, Sweden.
Sundberg
C
C
Andersson
K
K
De Pierre
J W
JW
D000818:Animals; D001835:Body Weight; D002210:Caprylates / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D002995:Clofibric Acid / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000652:urine; D004435:Eating; D005227:Fatty Acids / Q000378:metabolism; D005466:Fluorocarbons / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D008830:Microbodies / Q000187:drug effects* / Q000502:physiology; D008930:Mitochondria, Liver / Q000378:metabolism; D010171:Palmitoyl Coenzyme A / Q000378:metabolism; D051381:Rats; D012643:Selenium / Q000172:deficiency*; D014018:Tissue Distribution
D002210:Caprylates; D005227:Fatty Acids; D005466:Fluorocarbons; D010171:Palmitoyl Coenzyme A; D002995:Clofibric Acid; C023036:perfluorooctanoic acid; D002374:Catalase; D012643:Selenium