Effect of diet and disulfiram on acetaldehyde blood levels after ethanol in UChA and UChB rats

Quintanilla, Marı́a Elena; Sepúlveda, Sebastián; Tampier, Lutske

doi:10.1016/0741-8329(93)90024-i

Cited by 8 publications

(6 citation statements)

References 14 publications

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“…It has been reported that NAD concentration in the whole liver rat is approx 0.35 mM (Schulman et al, 1974). Moreover, the fact that we have not observed genetic differences in the liver mitochondria1 ALDH (Tampier et al, 1985;Quintanilla et al, 1993) may be because the in vitro experiments were performed at saturating concentrations of NAD (0.5 mM). The experiments on the in vitro effect of disulfiram excludes the possibility that the strain difference is caused by different disposition of disulfiram.…”

Section: Discussionmentioning

confidence: 50%

“…Some of the effects of ethanol on the cardiovascular and central nervous systems have been suggested to result from the formation of acetaldehyde (AcH). Acetaldehyde levels are controlled by aldehyde dehydrogenase (ALDH), whose activity is inhibited by drugs such as disulfiram (Hald & Jacobsen, 1948;Truitt & Walsh, 1971), some hypoglycaemic agents such as chlorpropamide and tolbutamide (Jerntorp et al, 1981(Jerntorp et al, , 1986 or by components in commercial animal diets (Marchner & Tottmar, 1976;Quintanilla et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

“…This is consistent with higher AcH blood levels in UChA than in UChB rats following pre-treatment with disulfiram and an i.p. dose of ethanol (Quintanilla et al, 1993;Tampier et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

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Acetaldehyde metabolism by liver mitochondrial ALDH from UChA and UChB rats: effect of inhibitors

1996

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We have observed that blood acetaldehyde (AcH) levels after an ethanol dose were significantly higher in disulfiram-pre-treated UChA (low ethanol consumer) than in UChB (high ethanol consumer) rats. In order to explore these results further, we studied the effect of disulfiram (300 mg/kg i.p.) and chlorpropamide (80) mg/kg i.p.) pre-treatment on blood AcH levels after oral ethanol (60 mmol/kg) and on AcH metabolism by liver mitochondrial aldehyde(s) dehydrogenase(s) from UChA and UChB rats. AcH metabolism by liver mitochondrial aldehyde dehydrogenase (ALDH) was studied by following AcH disappearance rate and the formation of NADH at 340 nm in the incubation medium. The results showed that chlorpropamide, like disulfiram, produced a higher blood AcH level consistent with a greater inhibition of the low-Km mitochondrial ALDH in the UChA rats than in the UChB rats. These drugs did not inhibit the high Km mitochondrial ALDH. Kinetic studies of mitochondrial ALDH show that low-Km mitochondrial ALDH from UChB rats exhibits a higher affinity for NAD than UChA rats. This observation could explain the different inhibition of ALDH by both drugs, assuming that the inhibitors reduce NAD availability, the rate limiting step in the mitochondrial ALDH oxidation.

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Section: Discussionmentioning

confidence: 50%

Section: Introductionmentioning

confidence: 99%

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Acetaldehyde metabolism by liver mitochondrial ALDH from UChA and UChB rats: effect of inhibitors

1996

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“…The dose of disulfiram used to inhibit ALDH activity does not change blood ethanol levels after an injected ethanol dose. 36 The higher acetaldehyde disappearance rate in brain homogenates of UChB rats (Table 3) explains the lower accumulation of acetaldehyde after ethanol oxidation with brain homogenates. The higher ALDH activity of UChB rats may be expressed only at non-saturating NAD levels, as is the case in our experimental condition.…”

Section: Discussionmentioning

confidence: 94%

Involvement of brain ethanol metabolism on acute tolerance development and on ethanol consumption in alcohol‐drinker (UChB) and non‐drinker (UChA) rats

Tampier

Quintanilla

2003

Addiction Biology

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Acute tolerance that develops in minutes of an ethanol exposure appears to influence voluntary ethanol consumption in our two selected bred lines, UChA (low ethanol drinker) and UChB (high ethanol drinker)rats. We have reported previously that an acute intraperitoneal (ip.) dose of ethanol (2.3 g/kg) induces both an increase in acute tolerance and a long-lasting increase in voluntary ethanol consumption in UChB rats. In the present paper we investigated the involvement of acetaldehyde produced centrally during ethanol oxidation by brain catalase and its oxidation by mitochondrial aldehyde dehydrogenase, on acute tolerance development and on voluntary ethanol consumption by rats. Acute tolerance developed to motor impairment induced by a dose of ethanol of 2.3 g/kg administered ip. was evaluated by the tilting plane test. Voluntary ethanol consumption by the rat with free access to a 10% v/v ethanol was measured daily. Both parameters were evaluated in controls,saline-pretreated and ethanol-injected rats. One group of rats that received the ethanol injection was pretreated with 3-amino-1,2,4-triazole (AT), a catalase inhibitor, and another group was pretreated with disulfiram, an aldehyde dehydrogenase inhibitor. Brain catalase and aldehyde dehydrogenase activities were measured in both groups of rats. Results show that acute tolerance to motor impairment, as well as ethanol consumption induced by ethanol, appears to be the consequence of acetaldehyde formed centrally during ethanol oxidation via the catalase system, because pretreatment of rats with the catalase inhibitor attenuated the increase in acute tolerance development and the increase in voluntary ethanol consumption in UChB rats that received the acute i.p. dose of ethanol. Moreover, the acetaldehyde metabolizing enzyme also appears to be an important factor in the modulation of acute tolerance development and voluntary ethanol consumption in UChA and UChB rats. The results lead us to propose that the possible mechanism by which the ip. injection of ethanol to UChB rats induces an increase in ethanol consumption is the development of acute tolerance, where acetaldehyde formed during brain ethanol metabolism via catalase and its subsequent oxidation via aldehyde dehydrogenase have an important role.

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“…This possibility was ruled out by performing a biological assay on extract ME-3451-106 using a method developed for Wistar UChB rats. The rats were later injected with a standard challenge dose of ethanol (Quintanilla et al, 1993;Tampier et al, 1994) and the blood acetaldehyde levels were determined by chromatographic techniques.…”

Section: Introductionmentioning

confidence: 99%

Effect of ME-3451-106, an aqueous extract of Stichaster striatus with inhibitory activity of voluntary alcohol intake, in genetically drinker rats: Isolation and identification of the active fraction

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et al. 2006

Journal of Ethnopharmacology

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Effect of diet and disulfiram on acetaldehyde blood levels after ethanol in UChA and UChB rats

Cited by 8 publications

References 14 publications

Acetaldehyde metabolism by liver mitochondrial ALDH from UChA and UChB rats: effect of inhibitors

Acetaldehyde metabolism by liver mitochondrial ALDH from UChA and UChB rats: effect of inhibitors

Involvement of brain ethanol metabolism on acute tolerance development and on ethanol consumption in alcohol‐drinker (UChB) and non‐drinker (UChA) rats

Effect of ME-3451-106, an aqueous extract of Stichaster striatus with inhibitory activity of voluntary alcohol intake, in genetically drinker rats: Isolation and identification of the active fraction

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