© 1989 Oxford University Press
research-article |
Changes in peroxisomes and mitochondria in liver of ethionine exposed rats: a biochemical and morphological investigation
1Laboratory of Clinical Biochemistry, University of Bergen Haukeland Sykehus, 5021 Bergen
2Zoological Laboratory, University of Bergen Haukeland Sykehus, 5021 Bergen, Norway
3Institute for Nutrition Research. University of Oslo Haukeland Sykehus, 5021 Bergen, Norway
4Clinical Pharmacological Unit. Department of Pharmacology, University of Bergen Haukeland Sykehus, 5021 Bergen, Norway
5To whom correspondence should be sent
Administration of ethionine resulted in a dose- and time-dependent enhancement of the activities of peroxisomal ß-oxidation, carnitine palmitoyltransferase and 
-oxidation, especially the 12-hydroxylation of lauric acid. The mitochondrial and, especially, the microsomal palmitoyl-CoA hydrolase activities were decreased. Ethionine administration decreased the catalase and urate oxidase activities in both a dose- and time-related manner. The liver cells and the volume fraction of cytoplasma decreased 40% in ethionine-exposed animals, whereas the average nuclei volume fraction increased 
50%. The volume fraction and the total number of mitochondria increased 1.5-fold after ethionine exposure and an accumulation of lipid in large droplets of the hepatocytes was observed. No proliferation of peroxisomes was observed after treatment; the volume fraction and the number of peroxisomes decreased. However, the size of peroxisomes in livers of ethionine-exposed rats tended to be greater than controls; a 1.5-fold increase in average size was observed. As there was no induction of the protein content of the bifunctional enoyl-CoA hydratase, an enzyme involved in peroxisomal ß-oxidation, it is considered that ethionine selectively stimulates the peroxisomal ß-oxidation due to increased peroxisome surface area rather than evoked a peroxisome proliferation capacity. Increased peroxisomal ß-oxidation was also observed in the kidney of ethionine-exposed rats at a dose of 750 mg/day/kg body weight. At that dose the amount of reduced glutathione (GSH) was significantly increased in kidney. The amount of GSH and the level of peroxisomal ß-oxidation were significantly increased in liver at an ethionine dose of 100 mg/day/kg body weight. These responses in liver were evident within 2 days of ethionine exposure and then leveled off whereas a significant increase in GSH and peroxisomal ß-oxidation in kidney was observed within 12 days. Whether the acute H2O2-generating peroxisomal oxidation of long-chain fatty acids in the liver may also make this organ susceptible to the long-term effects of low-dose ethionine and be an important step in the chain of events which eventually results in tumour development should be considered.