Effect of choline-deficiency and methotrexate administration on peroxisomal β-oxidation, palmitoyl-CoA hydrolase activity and the glutathione content in rat liver

Abstract

Hepatic metabolism of long-chain fatty acids was studied in male rats fed a defined choline-deficient (CD) diet with and without choline and after methotrexate (MTX) administration. Peroxisomal beta-oxidation was increased approximately 4-fold in the peroxisome-enriched fraction of CD-fed animals, whereas the catalase activity was increased 1.3-fold. The urate oxidase activity was marginally affected. The CD-fed rats also revealed elevated capacity for hydrolysis of palmitoyl-CoA in the cytosolic fraction (2.0-fold), whereas the microsomal palmitoyl-CoA hydrolase activity was decreased. Notably, the increased peroxisomal beta-oxidation, the catalase activity and palmitoyl-CoA hydrolase activities (the membrane-bounded and cytosolic) were almost fully prevented by adding choline to the CD-diet. Thus, the change in these enzyme activities appears to be a consequence of a choline-deficiency provoked by the CD diet. MTX administration of normal fed rats (ND diet) had no effects on the peroxisomal beta-oxidation, catalase activity and urate oxidase activity. MTX treatment of the ND-fed animals, however, increased the mitochondrial palmitoyl-CoA hydrolase activity and decreased the microsomal enzyme activity. As choline-deficiency and MTX increased the hepatic lipid level, the overall results suggest that fat accumulation is not an 'induction signal' for increased peroxisomal beta-oxidation. The CD diet alone increased the reduced glutathione content in liver, whereas MTX did not significantly change this level. Whether the changes of H2O2-generating peroxisomal oxidation of long-chain fatty acids may be an important step in a chain of events, which eventually results in tumour formation by choline-deficiency, should be considered.

Clofibrate pretreatment in mice confers resistance against hepatic lipid peroxidation

“…However the task is simplified somewhat because several laboratories have studied the effect of peroxisome proliferators on the major antioxidant systems in liver. Contrary to the expectations raised by our work, in most of these studies little or no change was seen in the hepatic levels of such antioxidant defense proteins such as catalase [60,61]; glutathione peroxidase [13,62]; glutathione reductase [63]; and superoxide dismutase [13,64].…”

Changes in peroxisomes and mitochondria in liver of ethionine exposed rats: a biochemical and morphological investigation

“…Thus, the cellular distribution of palmitoyl-CoA hydrolase in ethionine exposed animals is not similar to the picture obtained with various peroxisome proliferators, i.e. hypolipidemic drugs (14,15), high-fat diet (24), choline deficiency (31) or to modulations in responses to altered physiological status, e.g. starvation (21) where there is an increased palmitoyl-CoA hydrolase activity.…”