Effects of dietary treatment with clofibrate, nafenopin or WY-14.643 on mitochondria and DNA in mouse liver.

Male C57bl/6 mice were administered clofibrate (0.5%, w/w), nafenopin (0.125%, w/w) or WY-14.643 (0.125%, w/w) in their diet for 4 days. Assay of eight mitochondrial marker enzymes, -i.e., malate and glutamate dehydrogenases (matrix markers), cytochrome oxidase and cytochromes c + c1 and a (inner membrane), adenylate kinase (intermembrane space) and monoamine oxidase and microsomal glutathione transferase (outer membrane)--and morphometric analysis of electron micrographs was used to examine hepatic mitochondria after treatment with these peroxisome proliferators. A moderate increase in the number of hepatic mitochondrial profiles, with a simultaneous decrease in the average size of these organelles, was observed. The total mitochondrial volume is apparently unchanged during this process. An important experimental consequence of the apparent decrease in mitochondrial size is the redistribution of a large portion of the total hepatic mitochondria from the 'nuclear' to the mitochondrial fraction. A similar effect was seen with rats.