Time-dependent effects of the hypolipidemic agent clofibrate on peroxisomes and mitochondria in mouse hepatocytes.
Mice of the NMRI strain were fed a diet containing 0.5% clofibrate up to 25 days to study its effect on peroxisomes and mitochondria in the hepatocytes. Liver samples were analyzed by electron microscopy after cytochemical staining for catalase using diaminobenzidine in order to detect all peroxisomes for a quantitative analysis. The liver weights increased significantly after two days of treatment and reached a maximal level of 40% over the control animals. The number of peroxisomal profiles increased 3- to 4-fold at maximal proliferation and their average area nearly doubled, hence the number of peroxisomes with large diameters was increased making a 5-fold increase within the total cytoplasmic area. The size distribution of the peroxisomes was changed at day two of treatment to a more spread and even distribution going up in a higher size range. The mitochondrial profiles were less affected but there was a slight increase in their number, a small decrease in average area, a transient decrease in axial ratio but no significant effects on their cytoplasmic fractional area. The frequency distribution of mitochondrial area was shifted somewhat to lower values by clofibrate. At the end of the treatment the hepatocytes contained about the same number of peroxisomal and mitochondrial profiles but the latter were still occupying a two-fold higher fractional volume of the cytoplasm. Mouse hepatocytes thus seem to be a good system for studies on peroxisomal biogenesis as is their counterpart in rats, although they differ in their levels of various peroxisomal enzymes.
Meijer
J
J
Department of Chemistry, Swedish University of Agricultural Science, Uppsala.
Starkerud
C
C
Granell
I
I
Afzelius
B A
BA
D000818:Animals; D002374:Catalase / Q000378:metabolism; D002994:Clofibrate / Q000494:pharmacology*; D005227:Fatty Acids / Q000378:metabolism; D006651:Histocytochemistry; D008099:Liver / Q000648:ultrastructure*; D008297:Male; D051379:Mice; D008830:Microbodies / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008854:Microscopy, Electron; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D013997:Time Factors
D005227:Fatty Acids; D002374:Catalase; D002994:Clofibrate