INTERSPECIES DIFFERENCES IN GLUTATHIONE-DEPENDENT DETOXICATION OF HYDROPEROXIDES IN SHORT-TERM CULTURES OF HEPATOCYTES

Whether the glutathione-dependent detoxication pathway of hydroperoxid es is functionally expressed in vitro is not known. The major componen ts of the system were studied in freshly isolated hepatocytes and thei r short-term primary monolayer cultures. The hepatocytes were derived from human organ donors. Sprague-Dawley rats, beagle dogs and cynomolg us monkeys. Species differences exist in the intracellular (reduced) g lutathione (GSH) content of freshly isolated hepatocytes. In particula r, the GSH content of rat hepatocytes is small in comparison with that in human cells. Monkey hepatocytes displayed the highest levels, foll owed by human. dog and rat cells. After 24 hr in culture. the GSH cont ent of the hepatocytes increased, in all the species studied. With res pect to the glutathione reductase activity, freshly isolated human hep atocytes showed a level that was half that found for monkeys and rats and was approximately 1.5-fold of the activity measured in dog hepatoc ytes. These differences were maintained during short-term culture. Whe n glutathione peroxidase activities were measured, using hydrogen pero xide or tertiary butylhydroperoxide as substrates, the highest values were seen for rat hepatocytes followed by human, monkey and dog cells. Thus, it is clear that hepatocytes of different species have differen t GSH-dependent detoxication capacities. Copyright (C) 1996 Elsevier S cience Ltd.