THE EFFECT OF ETHANOL EXPOSURE ON COCAINE TOXICITY IN RAT HEPATOCYTES

The use of ethanol is common among the cocaine-abusing population. Bot h of these agents have been associated with hepatotoxicity. This inves tigation employed an in vitro model to study cocaine and ethanol inter actions in the liver. Hepatocytes (2 x 10(6) cells/ml) isolated from m ale Sprague-Dawley rats were exposed to saline, cocaine, ethanol or th e combination of cocaine and ethanol. Cell membrane damage in hepatocy tes was assessed by the uptake of 0.4% trypan blue and the leakage of the enzymes aspartate aminotransferase (AST) and alanine aminotransfer ase (ALT) into the incubation media; An increase in trypan blue uptake was observed following exposure to 5 mM cocaine as early as 30 min of incubation. Hepatocytes were unaffected by treatment with 25 and 50 m M ethanol for the 2-hr time period studied. Including ethanol in incub ations containing 1 or 5 mM cocaine did not result in any additional t oxicity when compared with hepatocytes treated with cocaine alone. How ever, AST leakage from hepatocytes exposed to cocaine in combination w ith ethanol was decreased when compared with hepatocytes treated with cocaine alone. These findings suggest that exposing hepatocytes simult aneously to cocaine in combination with ethanol, under the conditions of this experiment, does not enhance the hepatocellular toxicity produ ced by cocaine alone. (C) 1997 Elsevier Science Ltd.