Administration Of Acetaldehyde Research Articles

The changes in activities of some ammonia metabolizing enzymes in liver and brain of rats intoxicated by chronic administration of acetaldehyde

Etude des effets de l'administration chronique d'acetaldehyde sur les activites glutamine synthetase, glutamate deshydrogenase et glutaminase synthetase dans le foie et cerveau de rat ainsi que sur la concentration d'ammonium sanguine. On montre une augmentation de toutes ces activites enzymatiques dans le cerveau, de meme dans le foie sauf pour la glutamate synthetase

Disposition of ethanol and acetaldehyde in late pregnant rats and their fetuses.

The pattern of ethanol and acetaldehyde appearance in blood after an oral ethanol gavage (4 g/kg body wt) was not different at 12 or 21 days' gestation compared to virgin rats. Five min after maternal ethanol administration, concentrations of ethanol in fetal blood were lower than in maternal blood; however, at 15 min after ethanol administration, fetal and maternal blood levels were similar. Ethanol concentrations in fetal blood and amniotic fluid were already at equilibrium 5 min after ethanol administration. Acetaldehyde concentrations in fetal blood and in amniotic fluid were undetectable at all the times investigated, with the exception of fetuses from two pregnant rats studied 3 h after ethanol administration. Alcohol dehydrogenase activity in fetal liver and in placenta at late pregnancy was very low or undetectable, suggesting a very low rate of ethanol oxidation in vivo. After intravenous administration of acetaldehyde (10 mg/kg body wt), blood acetaldehyde concentrations were higher in pregnant than in virgin rats. Acetaldehyde concentrations in fetal blood and in amniotic fluid were similar to maternal blood at 2, 5, and 30 min after injection. When circulating concentrations of maternal and fetal acetaldehyde, obtained after either ethanol or acetaldehyde administration, were plotted, it was found that fetal blood concentrations of acetaldehyde were only detectable when maternal blood concentrations were greater than 80 microM. Concerning the acetaldehyde oxidation capacity, both the high and low affinity components of aldehyde dehydrogenase activity in fetal liver and placenta were very low as compared with maternal liver. However, aldehyde dehydrogenase activity in fetal liver was much higher than in placenta.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in sulfhydryl compounds in plasma, liver and brain after acute and chronic acetaldehyde administration in rats

The content of sulfhydryl compounds in proteins and non-proteins of plasma, liver and brain after acute and chronic administration of acetaldehyde (ACH) was investigated in rats. After ACH 1.5% w/v ingestion for 1 and 4 weeks (0.3 ml/kg) daily, proteins and non-proteins in plasma and liver were decreased significantly. After acute ACH administration SH-groups in brain proteins were not significantly decreased, but in the brain non-proteins these groups were increaed significantly.

Lipid peroxidation of hyperlipemic rat serum lipoproteins in chronic ethanol and acetaldehyde administration

The levels of lipid peroxides in circulatory lipoproteins increased with chronic administration of ethanol or acetaldehyde. Low density lipoprotein showed a greater increase in its content of lipid peroxides than very low density lipoprotein or high density lipoprotein. However, very low density lipoprotein was more prone to lipid peroxidationin vitro than low density lipoprotein or high density lipoprotein. The effect of acetaldehyde was more marked than that of ethanol. Lipoproteins of control and hyperlipemic groups were partially protected against peroxidation by butyrated hydroxytoluene and serum high density lipoprotein of normal rats.

Acute ethanol and acetaldehyde administration produce similar effects on L-type calcium channels in rat brain

The present study investigates the effect of acute ethanol and acetaldehyde administration on neuronal L-type calcium channels by measuring the binding of 3H-nitrendipine ( 3H-NTP). Acute ethanol (3 g/kg orally) transiently increases (+40% at 40 min) 3H-NTP binding. Acetaldehyde has a similar effect, but the onset of action is shorter; in fact the binding increase peaks 15 min following administration and is completely reversible within 2 hours. Disulfiram pretreatment does not modify the effect produced by acute ethanol on 3H-NTP binding. The results indicate that acetaldehyde may participate in mediating the action of ethanol on voltage sensitive L-type calcium channels with consequent alterations of neuronal excitability.

Effect of chronic acetaldehyde intoxication on ethanol tolerance and membrane fatty acids

Recent studies have suggested that acetaldehyde participates directly in the pathogenesis of alcoholism. Its action has been attributed mainly to its physico-chemical properties. Results of direct intoxication of laboratory animals with acetaldehyde have been reported, but only for short periods of exposure and at high doses. These are probably not representative of the conditions found during alcohol intoxication. The pulmonary route of administration described here enables long term intoxication with acetaldehyde, at levels corresponding to values measured during chronic ethanol intoxication. Chronic administration of acetaldehyde during 3 weeks induced a metabolic tolerance to ethanol as tested by the sleeping time after a challenge dose of ethanol; behavioural tolerance (measured by blood alcohol levels on waking) was not observed. At the end of the intoxication, phospholipid fatty acids of erythrocyte and synaptosome membranes were also analysed. Small changes in levels of the shorter fatty acids were observed in the phosphatidyl-choline fraction. By comparison with the effects of ethanol on the same membrane preparations, only a small part of this effect can be attributed to acetaldehyde. The first metabolite of ethanol has, however, a sure effect on the pattern of fatty acid phospholipids.

Lipoprotein-X in hyperlipemic rat serum in chronic ethanol and acetaldehyde administration

The levels of lipoprotein-X in circulation increased with chronic administration of ethanol or acetaldehyde. A similar profile was seen in rat serum with alkaline phospha- tase activity and bilirubin content. Total cholesterol, phospholipids and triglyceride con- tents increased followed by a decrease by progressive feeding with ethanol or acetaldehyde. The effect of acetaldehyde was more pronounced than that of ethanol.

Can brain lesions occur in experimental animals by administration of ethanol or acetaldehyde?

In a series of experimental studies involving ethanol vapour administration to rats, sustained blood alcohol levels in the range 89-115 mM for nine hours of each day over a two week period did not lead to neural degeneration detactable with either light or electron microscopy. A single nine hours exposure to ethanol and disulfiram giving rise to 20-41 mM alcohol and 52-76 microM acetaldehyde in the blood did lead to degeneration; and that with repeated exposures of this later type, the damage was found to be accumulative. The lowest levels of blood acetaldehyde which led to neural degeneration in the present study were not distant from clinically observed levels.

BLOOD PLASMA PEPTIDES OF RATS AFTER ADMINISTRATION OF ETHANOL OR ACETALDEHYDE

The blood plasma peptide fractions labelled with 3H-leucine after chronic administration of ethanol or acetaldehyde in rats have been analysed. Total 3H-leucine radioactivity in peptide fraction calculated per millilitre of plasma in both study groups was significantly decreased. The amount of peptide spots obtained by tlc in the ethanol-treated group or acetaldehyde-treated group was reduced in comparison with the control group. Analysis of amino acid composition of atypical spots occurring in both test groups revealed the presence of aromatic amino acids and methionine, but was associated with the absence of branched-chain amino acids, such as valine, leucine and isoleucine. These findings suggest a change in protein metabolism in hepatic dysfunction in rats receiving ethanol or acetaldehyde.

Plasma and liver amino acids in rats after administration of ethanol or acetaldehyde.

The changes in the level and pattern of free amino acids in plasma and liver after ethanol or acetaldehyde intoxication has been investigated in rats. After administration of 30% (w/v) ethanol, 6 g kg-1, or 1.5% (w/v) acetaldehyde, 0.3 ml kg-1, for 4 weeks we found a decrease in plasma and liver branched-chain amino acids and an increase in plasma aromatic amino acids and methionine. The results are analogous to those found in studies of damaged liver.

Cardiorespiratory inhibitory reflex induced by intravenous administration of acetaldehyde in rats

In urethane anesthetized rats, intravenous administration of a bolus of acetaldehyde (diluted 50 times its volume in Ringer Locke solution) induced after a latency of about 1 second, a triple reflex response characterized by transient bradycardia, hypotension and apnea. Intensity of both bradycardia (r=−0.78) and hypotension (r=−0.74) were dose dependent ( p<0.001). The triple response was blocked by vagotomy. Atropine and hexamethonium blocked bradycardia and hypotension and pretreatment of rats with reserpine (0.5 mg/100 g b.wt., IP) did not change the magnitude of the reflex response. The bolus effect was discarded by injecting the same volume of Ringer Locke solution in control test experiments. Administration of acetaldehyde directly into the left ventricle induced neither bradycardia nor hypotension, thus discarding a Bezold-Jarish reflex response. Administration of acetaldehyde directly into the right ventricle induced an increase in reflex bradycardia, hypotension and apnea with a shorter latency as compared to the intravenous route. The results suggest that the response induced by acetaldehyde is mediated by a reflex increase in vagal tone and probably is initiated in pulmonary vagal afferent fibers associated with the pulmonary J receptors.

Morphological and biochemical changes of the pancreas in rats treated with acetaldehyde

Daily intraperitoneal injections of acetaldehyde for 10 days to adult rats produced distinct morphological and biochemical changes in the exocrine pancreas, without affecting the body weight, pancreatic weight, and DNA, RNA, and protein content of the pancreas. By electronmicroscopy, although the number and size of the acinar zymogen granules appeared to be the same between the saline- and acetaldehyde-treated rats, the zymogen granules of the latter group showed decreased osmiophilia. Acinar mitochondria of the acetaldehyde-treated rats were found to be slightly swollen with dense granules, and plasma membrane fragments were often seen in the acinar lumen. Administration of acetaldehyde significantly decreased immunoreactive cationic trypsin (ogen) and total amylase activity in the pancreas, but not in the serum, where amylase activity was markedly increased. Basal secretion of amylase, trypsinogen, and chymotrypsinogen from isolated dispersed pancreatic acini of acetaldehyde-treated rats was increased by 40-50%. Nicotine (5-25 mM) induced a profound increase in secretion of the same enzymes from isolated acini of both saline- and acetaldehyde-treated rats, but in the latter group there was a concomitant rise in LDH release. Furthermore, CCK-8 (1 nM), secretin (1 microM), and carbachol (10 microM) either alone or in combination with nicotine (12.5 mM) produced a profound stimulation in amylase, trypsinogen, and chymotrypsinogen secretion from acini of both groups of rats. On the other hand, secretion of 3H-pulse-labeled proteins from isolated acini of acetaldehyde-treated rats by nicotine was decreased by approximately 50% compared with the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of chronic administration of acetaldehyde by inhalation on (Na + + K +)-activated adenosine triphosphatase activity of rat brain membranes

The effect of chronic acetaldehyde inhalation on (Na + + K +-ATPase (EC 3.6.1.3) activities of subcellular fractions of the rat cerebral cortex was studied. Chronic administration of acetaldehyde by inhalation for 4–21 weeks caused significant increases in the enzyme activities of both the synaptosomal plasma membrane (SPM) fraction and the microsomal(MC) fraction. This indicates the change in neural membrane functions of the brain after acetaldehyde treatment. Mg 2+-ATPase activities of both subcellular fractions remained unchanged after acetaldehyde treatment.

Thiamin depletion after ethanol and acetaldehyde administration to rabbits.

The role of thiamin in the catabolism of ethanol and acetaldehyde has been investigated. When thiamin and subsequently ethanol were administered orally to rabbits, the thiamin concentration in blood increased slightly during the first 3 h and then decreased gradually. After 12 h, it became lower than the value before thiamin administration. Finally, it reached the lowest value after 24 h and then increased slowly to revert to normal in 72 h. It is suggested that thiamin participates in the catabolic pathway of ethanol. An oral administration of pyrazole, an inhibitor of alcohol dehydrogenase, followed by ethanol to rabbits caused a delay in ethanol elimination from blood. When acetaldehyde was injected intravenously to rabbits, thiamin concentration and the transketolase activity in blood decreased gradually and after 12 h the thiamin level reached its lowest value, then increased slowly and normalized in 72 h. Thus, it could be postulated that the decrease in thiamin after an acute ethanol ingestion linked greatly to the acetaldehyde catabolism.

Catecholamines in the mechanism of the cardionecrotic action of acetaldehyde

Administration of acetaldehyde to rats by inhalation or intraperitoneally (in repeated doses) provokes an emergence of micronecroses in the myocardium. Administration of acetaldehyde in a dose causing no injury to the myocytes potentiates the cardionecrotic action of adrenalin. Pretreatment with L-DOPA potentiates while that of L-alpha-methyl-DOPA or alpha-methyl-p-tyrosine averts the necrosogenous action of acetaldehyde. Under isolated heart perfusion, acetaldehyde administered in the concentrations that exceeded 2-fold and more those in the blood in experiments in vivo had no necrosogenous action. The degree of the adrenalin-induced lesions of the isolated myocardium remained unchanged in the presence of acetaldehyde. It is assumed that the cardionecrotic effect of acetaldehyde is mediated by catecholamines and is effected by stimulation of biogenic amine release from neurons and chromaffin tissue, and is not linked with direct acetaldehyde effect on the realization of the alterative action of catecholamines.

Voluntary ethanol consumption after ethanol and acetaldehyde treatment in alcohol-preferring C57BL mice.

C57BL mice normally show a preference for alcohol solutions compared with water. The effect of chronic ethanol treatment sufficient to produce behavioural tolerance on the voluntary ethanol consumption of C57BL mice was compared with the effect of acute ethanol and acute and chronic administration of acetaldehyde. Chronic treatment with ethanol caused a loss of preference which lasted more than 12 weeks after withdrawal from the treatment. The acute ethanol treatment and the acute and chronic acetaldehyde treatments only produced a transient loss of preference which returned to normal within 1 week of cessation of treatment. The effect of these drugs on liver alcohol dehydrogenase (LAdH) was also examined. Changes in LAdH activity did not correlate with alcohol preference. Possible reasons for the different effects of the drug treatments on alcohol preference are discussed.

Effect of ascorbic acid or thiamine on acetaldehyde, disulfiram-ethanol- or disulfiram-acetaldehyde-induced mortality.

Ascorbic acid or thiamine was administered, i.p., to male mice 1 1/2 hours prior to i.p. administration of acetaldehyde. Ascorbic acid reduced acetaldehyde mortality at doses between 16 mmole/kg to 18 mmole/kg. Thiamine reduced acetaldehyde-induced mortality at lower acetaldehyde doses (16 mmole/kg) but not at higher doses (17 and 18 mmole/kg) that induced 100% mortality. Simultaneous coadministration of acetaldehyde and ascorbic acid caused a reduction in mortality. The effect of ascorbic acid or thiamine pretreatment on disulfiram-ethanol-induced mortality was investigated. A single dose of thiamine (0.24 mmole/kg) given 1 1/2 hours prior to administration of ethanol (11 mmole/kg to 88 mmole/kg) in disulfiram-treated mice reduced disulfiram-ethanol-induced mortality but a single dose of ascorbic acid (2 mmole/kg) pretreatment had no effect. Increasing the ascorbic acid pretreatment dosage schedule to three days resulted in a reduction of disulfiram-ethanol mortality. These results indicate that thiamine HCl was more potent than ascorbic acid in reducing the mortality induced by acetaldehyde or disulfiram-ethanol. The effect of disulfiram on ascorbic acid or thiamine activity toward reduction of acetaldehyde-induced mortality was investigated. The same three-day pretreatment condition for disulfiram and ascorbic acid or thiamine was used in mice as in the above disulfiram-ethanol study. In the third day, acetaldehyde was given to the mice. Either vitamin was ineffective in reducing the mortality induced by disulfiram-acetaldehyde.

Urinary sulfur containing metabolites after administration of ethanol, acetaldehyde and formaldehyde to rats

Acetaldehyde and formaldehyde react in vitro with cysteine to form a product, probably a thiazolidine derivative, which eluted as a single peak in cation exchange chromatography. The reactivity of formaldehyde was much higher than that of acetaldehyde. Rats were injected with single dose of 7.6, 6.2 and 2.5 mmol, respectively of ethanol, acetaldehyde and formaldehyde, and urine was analysed for alkalihydrolysable thiol groups. Acetaldehyde caused a significant increase in urinary alkali-hydrolysable thiols. Ethanol and acetaldehyde treatment stimulated the ability of the urine to catalyse the iodine-azide reaction suggesting the presence of an excess of compounds containing C-S-atoms.

Liver lipoperoxidative pressure and glutathione status following acetaldehyde and aliphatic alcohols pretreatments in the rat

Acetaldehyde administration (0.3 g/kg) to rats fasted overnight induces a reduction in liver reduced glutathione (GSH) content and stimulates lipid peroxidation. An additive effect in the decrease in liver GSH is observed when a non-peroxidating dose of ethanol (3 g/kg) is given previously to acetaldehyde, resulting in GSH levels similar to those elicited by 5 g of ethanol/kg. The administration of equivalent doses of n-propanol, i-propanol, n-butanol and t-butanol produces a progressive abolishment of the decrease in liver GSH content and of the increase in lipoperoxidation, compared to ethanol ingestion. These changes are correlated with the reactivities of alcohol dehydrogenase and microsomal alcohol oxidizing system with the alcohols studied.

Failure of acetaldehyde or acetate to mimic the splanchnic arteriolar or venular dilator actions of ethanol: direct in situ studies on the microcirculation.

The effects of acetaldehyde and sodium acetate on rat mesenteric arterioles (17-25 micron i.d.) and muscular venules (35-50 micron i.d.) were examined in situ, at the microcirculatory level, by use of a high-resolution closed circuit television microscope recording system. Local, intravenous or intra-arterial administration of acetaldehyde (1.8-3600 mumol) and sodium acetate (0.25-250 mumol) to mesenteric arterioles and muscular venules of the anaesthetized rat induced dose-dependent vasoconstriction. Systemic administration of a variety of pharmacological antagonists (i.e., phentolamine, diphenhydramine, methysergide, atropine and indomethacin) did not attenuate or prevent the dose-dependent vasoconstrictor actions of these metabolites of ethanol. Our findings do not support the concept that some or all of the peripheral vasodilator actions of ethanol can be attributed to its metabolites, acetaldehyde and acetate.