Influence of cyclosporin A treatment on intracellular membranes of hepatocytes.

The effect of cyclosporin A treatment on rat hepatocytes was investigated using both short and prolonged exposure to the drug. During a 5-week period of high dose treatment. body weight, liver weight, protein content, and phospholipid content decreased somewhat, while the protein per phospholipid ratio in the isolated mitochondrial, microsomal, and peroxisomal fractions remained unchanged. Mitochondrial cytochrome oxidase activity increased considerably, and carnitine acetyl transferase decreased. The respiratory control ratio was completely intact and the level of oxidative phosphorylation was unchanged. The two microsomal electron transport chains exhibited inverse behavior: the NADH oxidizing system increased while the NADPH counterpart decreased. Contrary to the known peroxisomal inducers, cyclosporin A decreases beta oxidation of fatty acids in addition to catalase and urate oxidase activities in isolated peroxisomes which may suggest an inhibition of certain steps in protein synthesis. When rats were treated with lower doses of cyclosporin A over a 15-month period, we observed effects that were similar in several aspects to the ones obtained after the shorter period of exposure.