Effects of aldehyde dehydrogenase inhibitors on enzymes involved in the metabolism of biogenic aldehydes in rat liver and brain

Hellström, Ewa; Tottmar, Olof

doi:10.1016/0006-2952(82)90308-2

Cited by 44 publications

(29 citation statements)

References 42 publications

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“…3B), probably because of brain ALDH acts as a metabolic barrier in the CNS, and there is evidence suggesting that low blood AcH concentration is not able to transport across the blood-brain barrier to enter the brain (Eriksson and Sippel 1977). CY is a potent ALDH inhibitor in the liver as well as in the brain (Deitrich et al 1976;Hellstrom and Tottmar 1982). Hence its presence led to an elevation in brain AcH concentration after a dose of EtOH, in agreement with our previous results (Jamal et al 2003c).…”

Section: Discussionsupporting

confidence: 89%

Failure of ethanol and acetaldehyde to alter in vivo norepinephrine release in the striatum and hippocampus of rats

et al. 2004

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The effect of ethanol (EtOH) and acetaldehyde (AcH) on norepinephrine (NE) release was examined in the striatum and hippocampus of freely moving rats by means of in vivo microdialysis coupled with high-performance liquid chromatography and an electrochemical detector. Rats were treated intraperitoneally with EtOH (1 g/kg) or cyanamide (CY, 50 mg/kg, a potent aldehyde dehydrogenase inhibitor) plus EtOH (1 g/kg). No significant difference in NE levels in the dialysates was observed in the striatum and hippocampus in either the EtOH or CY+EtOH groups. NE levels in the hippocampal dialysates were about fivefolds higher than those in the striatum. The concentration of EtOH and AcH in the striatal dialysate reached a peak at 30 min after EtOH dosing and then gradually decreased in the CY+EtOH group. In the EtOH group the striatal concentration of EtOH also reached a peak at 30 min after EtOH dosing, and then gradually decreased while AcH was not detected. The present study suggests that there is no in vivo effect of brain EtOH or AcH on NE release in the striatum and hippocampus of awake rats.

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Section: Discussionsupporting

confidence: 89%

Failure of ethanol and acetaldehyde to alter in vivo norepinephrine release in the striatum and hippocampus of rats

et al. 2004

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“…The low-Km mitochondrial isozyme is believed to be responsible for oxidizing ethanol-derived acetaldehyde (Marjanen 1973;Deitrich & Siew 1974;Eriksson et al 1975;Hellströ m & Tottmar 1982).…”

mentioning

confidence: 99%

Differentiation of Disulfiram Effects on Central Catecholamines and Hepatic Ethanol Metabolism

Karamanakos¹,

Pappas

Stephanou

et al. 2001

Pharmacology & Toxicology

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Disulfiram is used in the treatment of chronic alcoholism, because of the unpleasant symptoms it provokes after ethanol intake. The underlying mechanism is believed to be the accumulation of acetaldehyde in the blood, due to inhibition of the liver aldehyde dehydrogenases. In addition, it is known that disulfiram also has some neurotoxic properties. The aim of our study was to investigate the relationship between the pharmacological and neurotoxicological properties of disulfiram with respect to the doses applied. Increasing doses of disulfiram (25, 50, 75, 100 and 150 mg/kg) were administered intraperitoneally to Wistar rats and the hepatic enzyme activities of alcohol and aldehyde dehydrogenases were measured. Also, in two brain subregions (midbrain and hypothalamus) the levels of noradrenaline, dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid were determined. The higher dose of disulfiram (150 mg/kg) produced lethal effects in all treated animals. Aldehyde dehydrogenase activities were inhibited by disulfiram in a dose-dependent way, while alcohol dehydrogenase was not affected at all. Concerning the levels of brain biogenic amines, disulfiram produced a significant reduction in noradrenaline and an increase in dopamine levels in both structures of the brain, in a dose-dependent way. However, the lowest dose applied (25 mg/kg) had no effects on brain catecholamines. It is known that high doses of disulfiram may cause severe encephalopathy and peripheral neuropathy in humans, which could be attributed to the impairment of the metabolism of brain biogenic amines, due to inhibition of dopamine-b-hydroxylase. Our experimental data show that disulfiram affects the level of brain biogenic amines at dose levels higher than those inhibiting the activity of aldehyde dehydrogenase. Therefore, in clinical practice 'disulfiram reaction' could still be achieved with a low dosage regimen not producing neurotoxicity.

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“…Besides, the DDTC inhibition on ALDH activity causes changes in peripheral (Yourick and Faiman 1991) and central ALDH activity (Faiman et al 1980;Hellstrom and Tottmar 1982).…”

Section: Discussionmentioning

confidence: 99%

Concurrent administration of diethyldithiocarbamate and 4-methylpyrazole enhances ethanol-induced locomotor activity: the role of brain ALDH

Escarabajal

Aragón

2002

Psychopharmacology

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Effects of aldehyde dehydrogenase inhibitors on enzymes involved in the metabolism of biogenic aldehydes in rat liver and brain

Cited by 44 publications

References 42 publications

Failure of ethanol and acetaldehyde to alter in vivo norepinephrine release in the striatum and hippocampus of rats

Failure of ethanol and acetaldehyde to alter in vivo norepinephrine release in the striatum and hippocampus of rats

Differentiation of Disulfiram Effects on Central Catecholamines and Hepatic Ethanol Metabolism

Concurrent administration of diethyldithiocarbamate and 4-methylpyrazole enhances ethanol-induced locomotor activity: the role of brain ALDH

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