Microsomal and cytosolic epoxide hydrolases, the peroxisomal fatty acid beta-oxidation system and catalase. Activities, distribution and induction in rat liver parenchymal and non-parenchymal cells.
A number of structurally unrelated hypolipidaemic agents and certain phthalate-ester plasticizers induce hepatomegaly and proliferation of peroxisomes in rodent liver, but there is relatively limited data regarding the specific effects of these drugs on liver non-parenchymal cells. In the present study, liver parenchymal, Kupffer and endothelial cells from untreated and fenofibrate-fed rats were isolated and the activities of two enzymes associated with peroxisomes (catalase and the peroxisomal fatty acid beta-oxidation system) as well as cytosolic and microsomal epoxide hydrolase were measured. Microsomal epoxide hydrolase, cytosolic epoxide hydrolase and catalase activities were 7-12-fold higher in parenchymal cells than in Kupffer or endothelial cells from untreated rats; the peroxisomal fatty acid beta-oxidation activity was only detected in parenchymal cells. Fenofibrate increased catalase, cytosolic epoxide hydrolase and peroxisomal fatty acid beta-oxidation activities in parenchymal cells by about 1.5-, 3.5- and 20-fold, respectively. The induction of catalase (2-3-fold) and cytosolic epoxide hydrolase (3-5-fold) was also observed in Kupffer and endothelial cells; furthermore, a low peroxisomal fatty acid beta-oxidation activity was detected in endothelial cells. Morphological examination by electron microscopy showed that peroxisomes were confined to liver parenchymal cells in untreated animals, but could also be observed in endothelial cells after administration of fenofibrate.
Institut für Toxikologie, Universität Mainz, Federal Republic of Germany.
P
P
Steinberg
L
L
Schladt
H P
HP
Dienes
C
C
Timms
F
F
Oesch
D000818:Animals; D002374:Catalase / Q000378:metabolism*; D003600:Cytosol / Q000201:enzymology; D004727:Endothelium / Q000201:enzymology; D004851:Epoxide Hydrolases / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D011345:Fenofibrate / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007728:Kupffer Cells / Q000201:enzymology; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008830:Microbodies / Q000201:enzymology; D008862:Microsomes, Liver / Q000201:enzymology; D010084:Oxidation-Reduction; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D005227:Fatty Acids; D000960:Hypolipidemic Agents; D011422:Propionates; D002374:Catalase; D004851:Epoxide Hydrolases; D011345:Fenofibrate