Alcohol, Vol. 10, pp. 381-385, 1993 0741-8329/93 $6.00 + .00 Printed in the U.S.A. All rightsreserved. Copyright o 1993PergamonPress Ltd. Effect of Diet and Disulfiram on Acetaldehyde Blood Levels After Ethanol in UChA and UChB Rats MARfA ELENA QUINTANILLA, 1 SANDRA SEPOLVEDA AND LUTSKE TAMPIER Department of Pharmacology, School of Medicine, University of Chile, P.O. Box 70. 000, Santiago 7, Chile Received 14 January 1993; Accepted 15 April 1993 QUINTANILLA, M. E., S. SEPOLVEDA AND L. TAMPIER. Effect of diet and disuO~ram on acetaldehyde blood levels ofter ethanol in UChA and UChB rats. ALCOHOL 10(5) 381-385, 1993.-Acetaldehyde (AcH) levels in blood samples taken from different zones of the vascular system 2 h after a p.o. dose of ethanol (2.76 g/kg) were studied in UChA (low ethanol consumer) and UChB (high ethanol consumer) rats fed a diet devoid of animal products, diet 1 (D,), and a diet containing fish meal, diet 2 (D2), and in rats pretreated with disulfiram (600 mg/kg p.o.). The results showed that, while there is no significant difference between UChA and UChB rats fed D, with respect to blood AcH levels and the basal activity of the hepatic mitochondrial high-affinity aldehyde dehydrogenase (AIDH), a significant strain difference was observed in rats fed D2, which induced high blood AcH levels in UChA rats but not in UChB ones. No strain differences were observed in blood ethanol levels in the two groups of rats. When rats fed D, were pretreated with disulflram, the raising of AcH blood levels induced by ethanol after disulfiram was significantly higher in UChA than in UChB rats in suprahepatic vein, femoral vein, and tail blood. This difference was concomitant with a greater inhibition of the hepatic mitochondriai high-affinity AIDH activity in UChA rats than in UChB ones, whether disulfiram was administered in vivo or in vitro, which excluded the possibility that the strain difference would be caused by a different bioavailability of disulfiram. A1DH inhibition Ethanol Acetaldehyde levels Rat strains Diet Disulfiram A relationship between blood acetaldehyde (AcH) levels and hepatic aldehyde dehydrogenase (AIDH) activities has pre- viously been observed in rats and mice with genetic differences in ethanol preference. In fact, Sheppard et al. (14) first sup- ported that ethanol-preferring (C57BL) mice exhibited higher AIDH activity and lower blood AcH levels after ethanol than ethanol-avoiding (DBA) ones. Later on, it was reported that lower blood AcH levels after ethanol associated with higher AIDH activity in fiver microsomal and mitochondrial frac- tions in ethanol-preferring AA rats than in ethanol-avoiding ANA rats (2,6). Furthermore, in disulfiram-pretreated mice, blood AcH levels following ethanol administration were significantly lower in C57BL mice than in DBA ones, suggesting a differ- ence in the fiver AIDH of the two strains (13). On the other hand, evidence of the influence of diet on blood AcH levels after the same ethanol dose in rats has been reported by Marchner and Tottmar (8). These authors demon- strated the presence of a cyanamide-like substance in a com- mercial diet that induces high blood AcH concentration during ethanol oxidation (9). Furthermore, rats fed a diet inducing high AcH blood levels exhibited reduced activity of hepatic low-Kin AIDH (8). In the same fine of facts, it was observed in our laboratory in 1982 that an unexpected change in a_commercial standard diet was accompanied by a drastic reduction in the voluntary alcohol consumption of our rats, genetically low (UChA) and high (UChB) ethanol consumers (10). Subsequently we found that rats of both strains fed that new diet exhibited a signifi- cant increase in blood AcH levels after ethanol administra- tion, concomitant with an inhibition of the AcH oxidizing capacity of fiver and brain homogenate (15). Blood AcH levels in rats fed this diet were much higher than the levels observed in rats fed balanced diet devoid of animal products, as well as higher than the levels reported in most other studies, except in experiments with disulfiram-treated animals. For this reason, a balanced diet without any animal product, diet 1 (DI), has been employed since 1982 in our rat colony. At the present time, however, it has not been established if a strain difference in blood AcH levels during ethanol oxida- tion similar to that found in strains of animals raised by ge- netic selection for high or low ethanol intake occurs in UChA ' To whom requests for reprints should be addressed. 381