The involvement of selenium in peroxisome proliferation caused by dietary administration of clofibrate to rats.
The effects of dietary treatment with clofibrate (0.5% w/w for 10 days) on the livers of selenium-deficient male rats were examined. The peroxisome proliferation (as determined by electron microscopy) in the livers of selenium-deficient animals was much less pronounced than in the case of selenium-adequate rats and no increase in peroxisomal fatty acid beta-oxidation (assayed both as antimycin-insensitive palmitoyl-CoA oxidation and lauroyl-CoA oxidase activity) was observed in the deficient animals. On the other hand, in selenium-deficient rats clofibrate caused increases in the specific activity of microsomal lauric acid omega- and omega-1-hydroxylation and an apparent change in mitochondrial size, seen as a redistribution of mitochondria from the 600 x g(av) pellet to the 10,000 x g(av) pellet, which were approximately 50% as great as the corresponding effects on control animals. Obviously, then, these three different effects of clofibrate are not strictly coupled and may involve at least partially distinct underlying mechanisms. Initial experiments demonstrated that peroxisome proliferation could be obtained by exposing primary hepatocyte cultures derived from selenium-deficient rats to clofibric acid (an in vivo hydrolysis product of clofibrate which is the proximate peroxisome proliferator), nafenopin or mono(2-ethylhexyl)phthalate. This finding suggests that selenium deficiency does not have a direct influence on the basic process(es) underlying peroxisome proliferation, but rather has indirect effects, influencing, for example, the pharmacokinetics of clofibrate and/or hormonal factors.
Olsson
U
U
Department of Genetic and Cellular Toxicology, Wallenberg Laboratory, Stockholm University, Sweden.
Garberg
P
P
Lundgren
B
B
Andersson
K
K
Hultenby
K
K
Bergstrand
A
A
Eriksson
A M
AM
Högberg
J
J
DePierre
J W
JW
D000818:Animals; D001835:Body Weight; D002478:Cells, Cultured; D002994:Clofibrate / Q000008:administration & dosage / Q000494:pharmacology*; D004032:Diet; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure*; D008297:Male; D008830:Microbodies / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure*; D008854:Microscopy, Electron; D008930:Mitochondria, Liver / Q000201:enzymology; D009929:Organ Size; D051381:Rats; D017208:Rats, Wistar; D012643:Selenium / Q000172:deficiency*
D005979:Glutathione Peroxidase; D005982:Glutathione Transferase; D012643:Selenium; D002994:Clofibrate