|Abstract or Summary
- The effects of L-ascorbic acid, thiamine HC1, or L-cysteine on
acetaldehyde blood levels and disposition were investigated in acetaldehyde-
treated rats. Rats were treated with ascorbic acid (2
mmoles/kg), thiamine (0.24 mmole/kg), or cysteine (2 mmoles/kg) one
hour before the administration of acetaldehyde (6 mmoles/kg). The
results show that each of these nutrient factors lowered acetaldehyde
blood levels but by different mechanisms. Ascorbic acid and thiamine
lowered acetaldehyde blood levels by increasing the apparent volume of
distribution. Cysteine lowered the blood levels by direct interaction
with acetaldehyde. Ascorbic acid and thiamine increased the half life
of acetaldehyde by 300% and 250%, respectively. Cysteine had no significant effect on either the half life or the volume of distribution
Disulfiram (1 mmole/kg/3 days) was used to inhibit the metabolism
of acetaldehyde. The effects of ascorbic acid, thiamine, or cysteine
on acetaldehyde blood levels and disposition were then investigated in
the disulfiram-acetaldehyde-treated rats. Ascorbic acid and thiamine
reduced the half life of acetaldehyde by 55% and 40%, respectively. Both agents increased the total body clearance, and reduced the volume
of distribution of acetaldehyde. Acetaldehyde blood levels were lowered by thiamine, but not by ascorbic acid. Cysteine had no significant effect on either the blood levels or the kinetic parameters of
acetaldehyde in the disulfiram-acetaldehyde-treated rats.
When ethanol (2 gm/kg) was used as an endogenous source of
acetaldehyde, ascorbic acid and thiamine showed no significant effects
on either the ethanol or acetaldehyde blood levels. Both agents,
however, reduced the total amount of acetaldehyde relative to ethanol.
Cysteine increased the blood levels and the half life of acetaldehyde.
It reduced the total body clearance, and increased the total amount of
acetaldehyde relative to ethanol, an effect opposite to those of
ascorbic acid and thiamine.
The effects of ascorbic acid, thiamine or cysteine on the blood
levels and disposition of ethanol and acetaldehyde were investigated
in disulfiram-ethanol-treated rats. Only ascorbic acid was effective
in lowering ethanol and acetaldehyde blood levels. It reduced the
half life of ethanol by 20%, and that of acetaldehyde by 24%.
Ascorbic acid also increased the total body clearance of ethanol by
It seems that the protective effects of ascorbic acid, thiamine
or cysteine against acetaldehyde-induced mortality, as formerly reported (Moldowan and Acholonu, 1982), may be due to the reduction in
acetaldehyde blood levels. Because ascorbic acid and thiamine in
creased the half life of acetaldehyde (in acetaldehyde-treated rats),
their use in chronic acetaldehyde exposure (such as in chronic alcoholism) may lead to acetaldehyde accumulation. Cysteine lowered acetaldehyde blood levels without affecting the half life or the
volume of distribution. It is less likely to lead to acetaldehyde
accumulation. However, the beneficial effect of cysteine seems to be
limited to exogenously administered acetaldehyde. Because cysteine
reduced the clearance and metabolism of acetaldehyde generated from
ethanol, its use in chronic alcoholism may not be recommended.
The protective effect of ascorbic acid against disulfiramethanol-induced lethality may be due to its ability to lower the
ethanol and acetaldehyde blood levels. The reduction in blood levels
is coupled with increase in ethanol and acetaldehyde disposition.