Effects of vitamin A deficiency on selected xenobiotic-metabolizing enzymes and defenses against oxidative stress in mouse liver

Male and female C57Bl/6 mice were rendered vitamin A-deficient, and the eff ects of this deficiency on certain xenobiotic-metabolizing enzymes and defe nses against oxidative stress were examined. Vitamin A deficiency significa ntly increased the levels of DT-diaphorase, glutathione transferase, and ca talase in the hepatic cytosolic fraction from male mice (5.2-, 1.6-, and 3. 5-fold, respectively), as well as from female mice (4.8-, 3.3-, and 2.4-fol d, respectively). In the hepatic mitochondrial fraction (containing peroxis omes) from male animals, the activities of urate oxidase and catalase were increased 3.4- and 1.7-fold, respectively. The activity of catalase in the mitochondrial fraction from female mice was not affected by vitamin A defic iency, whereas the activity of peroxisomal urate oxidase was increased 2.9- fold. The hepatic level of ubiquinone was increased somewhat. The significa nce of the increases observed here is presently unclear, but it may be spec ulated that vitamin A and/or its metabolites are somehow involved in the do wn-regulation of these proteins. Another possibility is that these enzymes are increased as a result of hepatic oxidative stress caused by vitamin A d eficiency. However, vitamin A deficiency had no effect on the activity of s uperoxide dismutase in this study, whereas the activity of glutathione pero xidase was slightly decreased (27%) in the hepatic cytosolic fraction from male mice. In addition, the hepatic level of ol-tocopherol was decreased dr amatically in the vitamin A-deficient animals. BIOCHEM PHARMACOL 59;4:377-3 83, 2000. (C) 2000 Elsevier Science Inc.