EFFECTS OF TAXOL ON ISOLATED RAT HEPATOCYTE METABOLISM

Taxol is a natural product, isolated from Taxus brevifolia, with incre asing clinical applications because of its potent antitumor activity. Although it is mainly metabolized in the liver, its effect on hepatocy te metabolism has been scarcely investigated. In this study, the respo nse of isolated rat hepatocytes to taxol was evaluated by correlating the changes observed in global indexes such as viability and heat diss ipation with those produced in oxygen consumption and intracellular me tabolites (ATP, fructose 2,6-bisphosphate, and lactate). The results i ndicate that taxol reduces aerobic metabolism, which induces an insuff icient increase of the ATP via anaerobic glycolysis. Moreover, incubat ions of isolated mitochondria with taxol indicate that the respiratory chain is directly affected by this drug.