Toxicological Sciences, Vol 49, 133-142, Copyright © 1999 by Society of Toxicology
O Strubelt, M Deters, R Pentz, CP Siegers and M Younes
We investigated the acute toxic and metabolic effects of 23-aliphatic
alcohols (16 saturated and 7 unsaturated) in the isolated perfused rat
liver at a concentration of 65.1 mmol/l (approximately 0.3% ethanol). The
capacity of the straight chain primary alcohols (methanol, ethanol,
1-propanol, 1-butanol and 1-pentanol) to release the enzymes glutamate-
pyruvate transaminase (GPT), lactate dehydrogenase (LDH) and glutamate
dehydrogenase (GLDH) into the perfusate was strongly correlated with their
carbon chain length. The secondary alcohols were less active in this
respect whereas branching of the carbon chain did not consistently change
alcohol toxicity. Unsaturation in the straight chain but not in the
branched chain alcohols was accompanied by an increase in toxicity. An
increased enzyme release was in general accompanied by, and correlated to,
reductions in oxygen consumption, bile secretion, and perfusion flow of the
isolated livers. Statistically significant correlations exist between
parameters of alcohol-induced hepatotoxicity and the membrane/buffer
partition coefficents of the alcohols. With the exception of methanol, all
alcohols tested increased the lactate/pyruvate ratio of the perfusate,
although this effect was not correlated to the degree of hepatic injury.
Hepatic ATP concentrations decreased in most cases in line with hepatic
injury and were particularly correlated with changes in oxygen consumption.
Hepatic concentrations of reduced glutathione (GSH) were only diminished by
the unsaturated alcohols, whereas an increase in hepatic oxidized
glutathione (GSSG) occurred only with some of the saturated alcohols.
Hepatic concentrations of malondialdehyde (MDA) increased after two
saturated and three unsaturated alcohols but did not correlate with other
parameters of hepatotoxicity. In conclusion, alcohol-induced hepatotoxicity
is primarily due to membrane damage induced by the direct solvent
properties of the alcohols. The consequences and relative contributions of
alcohol metabolization to the overall hepatotoxicity of higher alcohols
requires further study.
ARTICLES
The toxic and metabolic effects of 23 aliphatic alcohols in the isolated perfused rat liver
Institut fur Toxikologie der Medizinischen Universitat zu Lubeck, Germany.
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