THE DISTRIBUTION OF NONSPECIFIC CARBOXYLESTERASES AND GLUTATHIONE S-TRANSFERASES IN DIFFERENT RAT-LIVER CELLS - EFFECTS OF VITAMIN-A-DEFICIENCY

Non-specific carboxylesterases (carboxylesterases) and glutathione S-t ransferases (GSTs) are two groups of drug metabolizing enzymes respons ible for hydrolysis and glutathione conjugation of xenobiotics. This s tudy was conducted to determine the following: (1) the distribution of carboxylesterase and GST activities in different rat liver cells, (2) the effects of vitamin A deficiency (A-) on the absolute activities a nd on the distribution of carboxylesterases and GSTs in rat liver. Rat livers were fractionated into parenchymal and non-parenchymal cells b y means of collagenase perfusion and differential centrifugation. Non- parenchymal cells were further fractionated by means of Percoll densit y gradient centrifugation into a layer of Kupffer cells and another la yer containing stellate and endothelial cells. Carboxylesterase and GS T activities were determined in these fractions. The results of the st udy show that: (1) both carboxylesterases and GSTs were mainly localiz ed in the parenchymal fraction, (2) there was no significant differenc e between male and female rats with regard total activity or distribut ion of carboxylesterases and GSTs in rat liver cells, (3) A- caused a highly significant reduction in carboxylesterase and GST activities in total liver homogenates and parenchymal cells. This reduction was not ameliorated by administration of retinoic acid 18 hr before sacrifice of animals. These results open up a new era of investigations about t he potential role of vitamin A in the regulation of detoxification enz ymes.