HEPATOTOXICITY AND ABSORPTION OF EXTRAHEPATIC ACETALDEHYDE IN RATS

Acetaldehyde, the first metabolite of ethanol oxidation, has been prop osed as a major initiating factor in ethanol-induced liver injury, The aims of this study mere to examine whether acetaldehyde is absorbable from the digestive tract and whether, when delivered chronically in d rinking water, it is capable of inducing liver injury in rats, Acetald ehyde concentrations in the rat portal and peripheral blood were measu red by head space gas chromatography after intragastric (5 ml) and int racolonic (3 ml) administration of 20 mM acetaldehyde solution, In the hepatotoxicity study, rats were exposed to acetaldehyde (20 and 120 m M) delivered in drinking water for 11 weeks and histopathological chan ges in the liver were morphometrically assessed, Peak blood acetaldehy de levels were found at 5 min after acetaldehyde infusion and were 235 +/- 11 mu M (mean +/- SE) after intragastric and 344 +/- 83 mu M afte r intracolonic infusion of 20 mM acetaldehyde solution, The exposure o f rats to 120 mM acetaldehyde solution for 11 weeks resulted in the de velopment of fatty liver and inflammatory changes, Morphometric analys is showed significantly more fat accumulation in rats receiving 120 mM acetaldehyde solution (85 +/- 2 per cent of hepatocytes occupied by f at) than in rats receiving 20 mM acetaldehyde solution (38 +/- 11 per cent) or in controls (36 +/- 10 per cent). The dose of extrahepatic ac etaldehyde (500 mg/kg per day) producing liver injury corresponds to o nly around 3 per cent of that derived from hepatic ethanol oxidation i n animals receiving an ethanol-containing totally liquid diet (15 g/kg per day), These results indicate that acetaldehyde delivered via the digestive tract can reach the liver by the portal circulation and that acetaldehyde of extrahepatic origin appears to be more hepatotoxic th an acetaldehyde formed during ethanol oxidation within the liver.