Synergism between aflatoxin B1 and oxytetracycline on fatty acid esterification in isolated rat hepatocytes

The individual and combined effects of aflatoxin B1 (AFB1) and oxytetracycline (OXT) on the synthesis and secretion of triacylglycerols in isolated rat hepatocytes maintained in suspension during 2.5 h were studied. Secretion of triacylglycerols was inhibited by both drugs when administered separately. This inhibition was accompanied by a concomitant elevation of intracellular triacylglycerols only at the highest AFB1 dose tested. Total synthesis of triacylglycerols was not inhibited by AFB1 or by OXT. When the two drugs were simultaneously added to the incubation medium, the AFB1-induced accumulation of intracellular triacylglycerols was no longer observed; the inhibition of secretion was nevertheless identical to that observed with AFB1 alone. Finally, total esterification of palmitate was inhibited by 20% compared to the AFB1-treated cells. These data suggest that OXT inhibits lipid accumulation induced by AFB1 but that this effect is due to an inhibition of total synthesis of triacylglycerols. The mechanism of AFB1's effect and of the interaction between both molecules is discussed.