Abstract
Glycerolipid synthesis and secretion in rat hepatocyte monolayer cultures have been studied as possible endpoints in cytotoxicity assays. Ten psychotropic drugs of different structural classes were incubated with the hepatocytes at concentrations ranging from 10(-6)m to 5 x 10(-5)m and their effects on the incorporation of [(3)H]glycerol into glycerolipids and on the subsequent lipid secretion into the medium were measured. After 2-hr exposures to eight of the ten drugs, glycerolipid secretion was inhibited as a function of the drug concentration. The integrity of the plasma membrane, however, was still preserved, as no leakage of the cytosolic enzyme, lactate dehydrogenase, occurred. The incorporation of [(3)H]glycerol into the total cell-associated glycerolipid fraction was much less affected by the drugs than was the medium-associated fraction. In this model, the tricyclic antidepressants, imipramine, clomipramine and amitriptyline caused a marked inhibition of in vitro glycerolipid secretion. Chlorpromazine, thioridazine, fluperlapine, haloperidol and promazine were of intermediate potency, and clozapine and sulpiride had no inhibitory effect on glycerolipid secretion. A significant inhibition of glycerolipid secretion was ...Continue Reading
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