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.

Total Glutathione and Glutathione Reductase in Bovine Erythrocytes and Liver Biopsy

“…Furthermore, the administration of ethionine induced an increase in the synthesis of the H 2 O 2 -generating peroxisomal beta-oxidation enzyme system in the rat liver. An imbalance between production and degradation due to high rates of the H 2 O 2 generating peroxisomal beta-oxidation system can cause an intrahepatic oxidation stress [1]. H 2 O 2 is a cytotoxic and can be converted to hydroxyl radical (.OH) via Fenton like reaction [18].…”

“…Catalase together with glutathione peroxidase (GSH-Px) plays an important role in the removal of H 2 O 2 from the cell, where H 2 O 2 is reduced to water [7]. Ethionine exposure was reported to inhibit hepatic catalase activity in rats [1], which activates the GSH-Px pathway to remove the excess H 2 O 2 . The endogenously produced H 2 O 2 is reduced by reduced glutathione (GSH) in the presence of selenium dependent GSH-Px; as a consequence, GSH is oxidized to glutathione disulfide, which is rapidly reduced back to GSH by glutathione reductase in the presence of nicotinamide adenine dinucleotide phosphate (NADPH) [23].…”