title: Changes in peroxisomes and mitochondria in liver of ethionine exposed rats: a biochemical and morphological investigation.
abstract: Administration of ethionine resulted in a dose- and time-dependent enhancement of the activities of peroxisomal beta-oxidation, carnitine palmitoyltransferase and omega-oxidation, especially the 12-hydroxylation of lauric acid. The mitochondrial and, especially, the microsomal palmitoyl-CoA hydrolase activities were increased, whereas the peroxisomal and cytosolic 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 approximately 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 beta-oxidation, it is considered that ethionine selectively stimulates the peroxisomal beta-oxidation due to increased peroxisome surface area rather than evoked a peroxisome proliferation capacity. Increased peroxisomal beta-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 beta-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 beta-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.
authors.affiliation: Laboratory of Clinical Biochemistry, University of Bergen, Norway.
authors.forename: N
authors.initials: N
authors.lastname: Aarsaether
authors.forename: A
authors.initials: A
authors.lastname: Aarsland
authors.forename: H
authors.initials: H
authors.lastname: Kryvi
authors.forename: A
authors.initials: A
authors.lastname: Nilsson
authors.forename: A
authors.initials: A
authors.lastname: Svardal
authors.forename: P M
authors.initials: PM
authors.lastname: Ueland
authors.forename: R K
authors.initials: RK
authors.lastname: Berge
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D002374:Catalase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005001:Ethionine / Q000494:pharmacology*; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D008297:Male; D008830:Microbodies / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D014503:Urate Oxidase / Q000378:metabolism
chemical_list: D007770:L-Lactate Dehydrogenase; D002374:Catalase; D005969:Glutamate Dehydrogenase; D009251:NADPH-Ferrihemoprotein Reductase; D014503:Urate Oxidase; D000135:Acid Phosphatase; D005001:Ethionine