Infusion Of Acetaldehyde Research Articles

Metabolic and hormonal changes during intravenous infusion of ethanol, acetaldehyde and acetate in normal and adrenalectomized rats

The effects of 30-min intravenous infusions of ethanol (about 50 m m blood concentration), acetaldehyde (about 100 μ m blood concentration), and acetate (equimolar dose to acetaldehyde) were studied in normal and adrenalectomized rats. Blood glucose, plasma free fatty acids (FFA), plasma immunoreactive insulin, and glucagon and hepatic glycogen concentrations were measured. Ethanol itself in the presence of 4-methylpyrazole (4-MP) produced no marked changes in the parameters measured. Its infusion without 4-MP reduced plasma insulin by 35% in the normal rats, but not in the adrenalectomized rats, with no simultaneous changes in blood glucose. Acetaldehyde infusion produced hyperglycemia and relatively slight hyperinsulinemia in the normal rats, but not in the adrenalectomized rats. Equimolar acetate was not as potent a stimulator of glycogenolysis as acetaldehyde. Plasma FFA concentrations were markedly reduced by ethanol (without 4-MP), acetaldehyde and acetate both in the normal and adrenalectomized rats, but in the presence of 4-MP ethanol was without effect. The results indicate that metabolites of ethanol (mostly acetaldehyde) produced during ethanol oxidation in vivo are responsible for the stimulation of glycogenolysis through the release of catecholamines from the adrenal glands. The ethanol-induced decrease in plasma FFA is also attributable to the metabolites of ethanol, acetaldehyde having a more potent depressing action than acetate. The mode of inhibition of lipolysis is not related to hormonal factors.

Acetaldehyde occurrence in cerebrospinal fluid during ethanol oxidation in rats and its dependence on the blood level and on dietary factors

After administration of ethanol to rats fed either an normal (I) or a cyanamide contaminated (II) standard laboratory diet, acetaldehyde and ethanol were determined in cerebrospinal fluid and blood. The acetaldehyde level in the cerebrospinal fluid from group I showed a plateau at approximately 30 μm while the blood concentration ranged from 20 to 60 μM. In group II the acetaldehyde in the cerebrospinal fluid varied according to the blood level. When the acetaldehyde in the blood of group I exceeded 50 μM after infusion of acetaldehyde, the concentration in cerebrospinal fluid started to rise. The ethanol concentration in the cerebrospinal fluid was correlated directly to the concentration in the blood independent of the type of feed. The difference in the occurrence of acetaldehyde in cerebrospinal fluid from the two groups may be explained by an inhibition of the brain aldehyde dehydrogenase with a low K m towards acetaldehyde.

Effects of length of exposure to and concentration of acetaldehyde on the release of catecholamines

The perfused isolated cow adrenal gland was stimulated to release catecholamines by perfusion with Tyrode solution containing acetaldehyde in concentrations between 1.5 × 10 −5 and 2.5 × 10 −2 M. Release per unit time (μmoles/min) of catecholamines by acetaldehyde increased as the length of exposure to the drug was increased. In contrast to carbachol, the concentration-response curve for acetaldehyde was shifted to the left by increasing the stimulation time 3-fold. A delay in reaching the maximum response was observed at 2 × 10 −3 M acetaldehyde; this delay increased as the concentration of acetaldehyde was lowered. Catecholamine release returned to its basal level upon terminating the infusion of acetaldehyde. It is concluded that acetaldehyde can release adrenal catecholamines at concentrations similar to those that occur in man after ingestion of alcohol, but a period of time is required for accumulation of an effective concentration of the drug at its site of action.

Pharmacological studies with antabuse.

1. In dogs, Antabuse decreases glomerular filtration. 2. Dogs tolerate Antabuse without evidence of liver damage. 3. Giving of Antabuse to dogs did not alter their response to paraldehyde. 4. An intravenous infusion of acetaldehyde in dogs causes a depression of the R wave in all leads in the electrocardiogram. 5. The regularity of the estrous cycle in rats is not affected by Antabuse.