EFFECTS OF CLOFIBRATE WITHDRAWAL ON PEROXISOMES IN MOUSE HEPATOCYTES

Adult male mice (NMRI strain) were initially treated with 0.5% clofibr ate in the diet during four days to obtain a high level of peroxisomes in the hepatocytes. Groups of animals were then given control diet fo r one, two, three, or four days. Liver samples were cytochemically sta ined for catalase prior to examination by electron microscopy and subs equent morphometric analysis. Various enzyme activities were assayed i n liver homogenates. A sixfold increase in peroxisomal area was found after four days of clofibrate feeding compared with untreated animals. The peroxisomal fractional area was unchanged after one day of refeed ing control diet but was reduced with over 50% after two days on contr ol diet and was similar to that in the untreated animals after four da ys. The size distribution of peroxisomes shifted to smaller values dur ing the breakdown of peroxisomes and was similar to the untreated anim als after four days of clofibrate withdrawal. During this process a mo re heterogeneous staining of peroxisomes was observed. The mitochondri al fractional area was not affected by the treatments, but a shift in size distribution to smaller values was observed in the most induced a nimals. Protein content was not affected by the treatments. The activi ty of catalase (twofold induction) decreased progressively to control values during recovery but enoyl-CoA hydratase activity (fourty-fold i nduction) decreased rapidly. NADPH-cytochrome c reductase activity (tw ofold induction) decreased rapidly to control levels. Citrate synthase activity was not affected by clofibrate treatment but decreased durin g recovery. Acid phosphatase activity (repressed) increased to control levels. Cathepsin D activity increased somewhat during recovery while proteolytic activity (towards casein) decreased transiently on contro l diet.