| Abstract: | 3-4 days after a single clinical dose of vincristine or vinblastine in rhesus monkeys there was a marked decrease in plasma low-density lipoprotein cholesterol concentrations. There was also a concomitant increase in plasma triacylglycerol concentrations. Plasma lipid levels returned to normal concentrations within 7-10 days after injection. Plasma high-density lipoprotein cholesterol concentrations were unaltered by the drugs. Electron micrographs of the hepatocytes from monkeys treated with vincristine or vinblastine showed an accumulation of glycogen particles and proliferation of smooth endoplasmic reticulum, which was accompanied by an increase in the number of lipoprotein-containing vesicles. These results indicate that vincristine and vinblastine alter plasma cholesterol and triacylglycerol concentrations in part by interfering with hepatic lipid and lipoprotein metabolism. These studies further suggest the possibility that other less cytotoxic alkaloids from Catharanthus species with clinically useful hypocholesterolemic activity may be discovered. |
