THE HEPATOTOXIC INTERACTION OF ORAL ETHANOL AND INHALED TOLUENE (TRIGLYCERIDE)
Abstract
The objective of this study was to evaluate the interactive hepatotoxicity of oral ethanol and inhaled toluene administered under substance abuse conditions. Male Sprague-Dawley rats were treated with ethanol and/or toluene. Ethanol treatments ranged from a single 4.5 g/kg oral dose to 29 days of continuous ingestion of ethanol in liquid diet form. Toluene treatment consisted of inhalation exposures to 4,000 or 10,000 ppm toluene vapor using various exposure regimens. No significant degree of hepatocellular necrosis was detected by means of measurement of serum or plasma enzyme activities. Acute treatments produced an additive increase in liver triglyceride concentration. Chronic treatments produced an additive increase in relative liver weight, a more than additive increase in liver triglycerides. Toluene decreased the elevation in plasma triglycerides due to ethanol. Withdrawal of ethanol 14 hours prior to toluene exposure attenuated the ethanol-toluene interaction concerning liver triglycerides, but did not alter the plasma triglyceride effect. Measurement of stress markers (plasma corticosterone, free fatty acid, and glucose concentrations) indicated that stress did not play a role in these interactions. Combined ethanol and toluene treatments decreased the rate of hepatic triglyceride synthesis and increased the rate of hepatic triglyceride synthesis and increased the rate of hepatic triglyceride secretion. A shift in lipoprotein relative abundance from the low density type to the very low density type also occurred in rats receiving combined treatments. Ethanol-withdrawn rats displayed an increased sensitivity to the narcotic action of toluene. In studies of acute exposure to ethanol, blood ethanol concentration fell during, and then increased after, toluene exposure of rats receiving a single dose of ethanol. No mechanisms for these effects were determined. These results indicate that concurrent exposure to alcohol and toluene produces hepatic changes which may predispose to an increased incidence or severity of alcoholic liver disease.
Degree
Ph.D.
Subject Area
Pharmacology
Off-Campus Purdue Users:
To access this dissertation, please log in to our
proxy server.