Biomedical subjects

M E Quintanilla

Publications and source records attributed to M E Quintanilla.

At least 19 recordsLinked to original sources

PubMed2003

Mutations in mitochondrial aldehyde dehydrogenase (ALDH2) change cofactor affinity and segregate with voluntary alcohol consumption in rats.

Genetic factors influence alcohol consumption and alcoholism. A number of groups have bred alcohol drinker and non drinker rat strains, but genetic determinants remain unknown. The University of Chile rat lines UChA (low drinkers) and UChB (high drinkers) display differences in the relative K(m) for NAD+ of mitochondrial aldehyde dehydrogenase (ALDH2) but no V(max) differences. The relative K(m) differences may be due to mitochondrial changes or to genetic differences coding for ALDH2. We investigated whether there are differences in the coding regions of ALDH2 cDNA in these lines and whether the Aldh2 genotype predicts the phenotype of alcohol consumption and the K(m) of ALDH2 for NAD+. Liver cDNA was prepared, and the Aldh2 transcript was amplified, cloned and sequenced. Genotyping was conducted by DNA amplification and restriction enzyme digestion. When compared to Aldh21 of Sprague-Dawley, 94% of the UChA (low drinker) rats (n = 61), presented a mutation that changes Gln67 to Arg in the mature enzyme (allele referred to as Aldh22). In UChB (high drinker) rats (n = 69), 58% presented the Aldh21 allele, while 42% presented the Gln67Arg change plus a second mutation that changed Glu479 to Lys (allele Aldh23). The Aldh22 allele was absent in high drinker rats. Rats of different Aldh2 genotypes displayed marked phenotypic differences in both ethanol consumption (g/kg/day; means +/- SE): (Aldh21/Aldh21) = 5.7 +/- 0.2, (Aldh22/Aldh22) = 0.9 +/- 0.2 and (Aldh23/Aldh23) = 4.6 +/- 0.2; and K(m)s for NAD+ of 43 +/- 3 microm, 132 +/- 13 microm and 41 +/- 2 microm, respectively (Aldh22 versus Aldh21 or Aldh23; P < 0.0001 for both phenotypes). Overall, the data show that alleles of Aldh2 strongly segregate with the phenotype of ethanol consumption and the relative K(m) for NAD+ of ALDH2. Bases mutated suggest that non drinker Aldh22 is ancestral with regard to the coding changes in either Aldh21 or Aldh23, variants which would allow ethanol consumption and may provide an evolutionary advantage by promoting calorie intake from fermented products along with carbohydrates.

Aldehyde Dehydrogenase↗

PubMed2001

Differences in sensitivity to the aversive effects of ethanol in low-alcohol drinking (UChA) and high-alcohol drinking (UChB) rats.

A conditioned taste aversion paradigm was used to determine whether aversion to the pharmacological effects of ethanol, apart from orosensory cues, can contribute to differences in voluntary ethanol consumption in rats of the low-alcohol drinking (UChA) and the high-alcohol drinking (UChB) strains. "Alcohol-naive" UChA and UChB rats were injected intraperitoneally with ethanol (0.5, 1.0, 1.5, or 2.0 g/kg) or saline, paired with consumption of a banana-flavored solution during five conditioning trials. Repeated pairings of banana-flavored solution and ethanol at a dose of 1.5 g/kg produced aversion to the banana-flavored solution in UChA rats, but not in UChB rats, at comparable blood ethanol levels. In addition, the highest dose of ethanol tested (2.0 g/kg) produced stronger aversion to the banana-flavored solution in UChA rats, compared with findings in UChB rats. From these results it is suggested that rats of the UChA strain find the postingestional effects of high-dose ethanol more aversive than do UChB rats. Differences in voluntary ethanol consumption seem to be associated with differences in sensitivity to the aversive effects of ethanol.

Alcohol Drinking↗

PubMed2000

Effect of naltrexone on acute tolerance to ethanol in UChB rats.

The effect of naltrexone (a non-selective opioid receptor antagonist) on both alcohol consumption in a voluntary selection situation and acute tolerance to the motor impairment effect of ethanol was examined in female high alcohol-drinking (UChB) rats using the tilting plane test. In experiment 1, the effect of naltrexone on alcohol consumption was studied in UChB rats which were given a daily 1-h period access to a 10% (v/v) ethanol solution with food and water always available. Naltrexone in doses of 5 or 10 mg/kg intaperitoneal (i.p.) caused dose-dependent reduction in voluntary alcohol intake by 45% and 66%, respectively, without altering daily water intake. In experiment 2, the effect of naltrexone (5 mg/kg i.p.) on acute tolerance to motor impairment effect of a dose of 2.3 g ethanol/kg i.p. was examined. A comparison of control (C) and naltrexone (Nal) UChB groups indicated that naltrexone slowed the recovery of the motor activity and reduce acute tolerance development at comparable ethanol levels in cerebral blood. These results suggest a contribution of the opioid system to acute tolerance to ethanol.

Alcohol Drinking↗

PubMed2000

Acute tolerance, alcohol sensitivity and drinking pattern in the F2 generation of UChA and UChB rats.

OBJECTIVE: Studies in mice and rats bred for their behavioral response to ethanol have revealed that there may be a relationship between acute tolerance development, sensitivity to ethanol and alcohol preference. We saw a need to obtain more genetically meaningful correlations between ethanol consumption and acute tolerance to motor impairment or sensitivity to hypothermia induced by ethanol. In the present article, we provide results on acute tolerance, sensitivity to hypothermia and voluntary ethanol consumption in an F2 generation of a cross between inbred UChA (low) and UChB (high) ethanol-consuming rats. METHOD: Naive UChA and UChB rats were tested for acute tolerance development to motor impairment and sensitivity to hypothermia induced by the intraperitoneal administration of a dose of ethanol of 2.3 g/kg body weight. Rats were then offered ad libitum a 10% v/v ethanol solution, distilled water and rat food, and classified according to their drinking scores. Next, one female UChA (low consumer) was mated with one male UChB (high consumer) and one female UChB (high consumer) mated with one male UChA (low consumer). The F2 generation of these inbred rats was used to test acute tolerance, sensitivity and voluntary ethanol consumption. RESULTS: UChB rats developed acute tolerance more rapidly and were less sensitive to the ethanol dose than UChA rats. The F2 generation was designated Hybrid A (HA) for those offspring from the UChA female grandparent and Hybrid B (HB) for the offspring from the UChB female. Results show clearly that there is a relationship between the ability of the rat to acquire acute tolerance to motor impairment, the sensitivity to hypothermia induced by ethanol, and the ethanol preference of the rat. The multiple correlation analysis between the three behaviors showed a significant value in HA rats (r = -0.76, p < .01) and in HB rats (r = -0.83, p < .01). CONCLUSIONS: This study of a cross between UChA and UChB rats showed that the three parameters are related since they clustered together in the F2 generation. This result leads us to speculate that if we could control acute tolerance development in the rats we might also control their voluntary ethanol consumption.

Alcohol Drinking↗

PubMed1996

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

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.

Journal Article↗

PubMed1994

Investigations on the ethanol-induced flushing reaction: effects of propranolol and dipyridamole on acetaldehyde and prostacyclin metabolism.

Disulfiram, an aldehyde dehydrogenase (ALDH) inhibitor, induces a flushing reaction upon the ingestion of ethanol, exerting aversion against alcohol that has been used in the treatment of alcoholism. This unpleasant response has been associated with an accumulation of acetaldehyde, and more recently, with an increase in vascular prostacyclin (PGI2) production. To evaluate the possibility of evoking the flushing reaction with drugs less toxic than disulfiram, we studied the effects of propranolol and dipyridamole on ALDH and PGI2. Acetaldehyde oxidation rate was assessed by gas chromatography in mitochondria from rats treated with these drugs for seven days. Prostacyclin generation was determined in rat aortic rings incubated in Krebs-Ringer with these drugs separately and associated to acetaldehyde, and measured by radioimmunoassay of 6-keto-PGF1 alpha. Propranolol inhibited acetaldehyde oxidation rate whereas dipyridamole did not. Furthermore, propranolol increased blood acetaldehyde levels without affecting ethanol elimination rate. Both drugs stimulated prostacyclin synthesis but only dipyridamole enhanced the stimulatory effect of acetaldehyde on vascular prostacyclin production. These results strongly suggest the possibility of producing a deterrent effect on the consumption of alcohol by using propranolol or dipyridamole. In contrast to disulfiram, these drugs could potentially induce the flushing reaction in humans in the presence of low acetaldehyde concentrations; this new therapeutic approach might have an important clinical and toxicological relevance.

Acetaldehyde↗

PubMed1994

Acetaldehyde metabolism: differences between UChA and UChB rats.

In order to explore the influence of acetaldehyde (AcH) metabolism on the voluntary ethanol intake of genetically low (UChA) and high (UChB) ethanol consumer rats, the AcH disappearance rate (ADR) after incubation with homogenates and subcellular fractions from liver and brain was determined. In addition, the effect of disulfiram pretreatment on AcH metabolism was studied. Male adult rats of both strains were used. ADR was assayed in total homogenates, and in mitochondrial as well as 9000 g supernatant fractions of liver and brain. AcH was measured by gas chromatography. In some experiments, rats were pretreated with disulfiram (300 mg/kg po) 24 hr before the studies. The result showed no strain difference in ADR in homogenates or subcellular fractions of liver from untreated rats, but for disulfiram pretreated rats a significantly lower decrease of ADR in samples from UChB compared to UChA rats was observed. This result is consistent with a lower peak AcH level in UChB compared to UChA rats after a load of ethanol (60 mmole/kg ip). Concerning brain homogenates, a higher ADR was observed in homogenates and crude mitochondrial fractions of UChB than of UChA rats. This difference was not observed when the incubation was performed without adding NAD or in the absence of oxygen. These results provide evidence of strain differences in mitochondrial AcH metabolism, the nature and origin of which deserve further study.

Acetaldehyde↗

PubMed1990

Acetaldehyde metabolism by isolated hepatic mitochondria from rats consuming different amounts of ethanol.

We have previously reported that in rats, ethanol intake as low as 4 g/kg per day induced mitochondrial alterations, detected by a decrease in mitochondrial O2 uptake supported by substrates entering at the three sites of coupled phosphorylation. Since it has been reported that acetaldehyde oxidation occurs mainly inside the mitochondria, linked to the respiration chain, the effect of daily previous administration of low doses of ethanol during a month, on the acetaldehyde oxidation rate by intact rat liver mitochondria was studied. Determination of acetaldehyde oxidation rate and O2 uptake accompanying acetaldehyde removal by liver mitochondria indicates that the mean value of these parameters studied in rats consuming low amount of ethanol (0.5-3.0 g/kg per day) was significantly higher than that of controls drinking only water (P less than 0.001, in state 3, and P less than 0.05, in state 4). This enhancing effect of ethanol cannot be ascribed to an uncoupling of oxidative phosphorylation and also not to a change in aldehyde dehydrogenase activity which was measured in disrupted mitochondria. On the other hand, high ethanol consumption (4-7 g/kg per day), which alters mitochondrial function, did not decrease mitochondrial acetaldehyde oxidation, as compared to rats drinking water only. This result differs from the decrease induced by higher levels of previous ethanol intake (12-14 g/kg per day) as reported by several authors, showing that possibly this effect is dose dependent.

Acetaldehyde↗

PubMed1989

Sensitivity of liver mitochondrial functions to various levels of ethanol intake in the rat.

Mitochondrial function appears to be an early target for ethanol toxicity, however it is not clear to what extent the effects of ethanol, which occur at levels of intake lower than those already reported in the literature, can induce an alteration of it. To produce different levels of ethanol intake, the spontaneous consumption of ethanol by genetically low (UChA) and genetically high (UChB) rats, as well as the forced intake obtained by offering 10% v/v ethanol solution as the only source of drinking fluid, were employed. The O2 uptake by liver mitochondria of rats submitted to these conditions in the presence of glutamate + malate, succinate or ascorbate + TMPD, was measured polarographically with a Clark electrode at 25 degrees C. Results indicate that alterations of the hepatic mitochondrial function can be detected at levels of ethanol intake much lower than those previously reported. Whereas, a level of a daily ethanol intake of 2-3 g/kg body weight in UChA rats under free choice was insufficient to produce detectable changes in the mitochondrial function, the latter was decreased in the high ethanol consumers (UChB), which drank 4-5 g/kg per day under free choice conditions, and in both strains forced to drink 10% ethanol as only source of fluid, which produced intakes of about 7 g/kg per day. Therefore, mitochondrial dysfunction may contribute to effects observed even at low levels of ethanol intake.

Alcohol Drinking↗

PubMed1985

Effects of diets decreasing ethanol consumption on acetaldehyde metabolism in UChA and UChB rats.

It has previously been reported that the introduction of a new issue (D1) of a stock diet (D0) caused a significant decrease in voluntary ethanol consumption in rats of our UChA (low ethanol consumer) and UChB (high ethanol consumer) strains, and that, after changing to a diet lacking in animal products (D3), ethanol consumption reached the previous level attained in UChB rats and exhibited a bimodal distribution in UChA rats in such a way that about one-third of these consumed more than 2 ml of a 10% (v/v) ethanol solution per 100 g of body weight, as did UChB rats. When UChA rats exhibiting high ethanol consumption and also UChB rats were fed on the D3 diet with a brewer's yeast supplement, a significant decrease in ethanol intake was observed. Since significant correlations of voluntary ethanol intake to blood acetaldehyde levels, and to hepatic and brain aldehyde dehydrogenase (AldDH) activities, have been reported, the effects on these parameters of diet D1 and of supplements of brewer's yeast or disulfiram were studied. Results showed that rats of both strains fed on a D1 diet exhibited a significant increase in blood acetaldehyde level after ethanol administration, concomitant with an inhibition of hepatic and brain AldDH activities and a significant decrease in ethanol intake. Thus, this effect could be related to a disulfiram-like activity. The decrease in ethanol intake induced by brewer's yeast was not accompanied by changes of blood acetaldehyde level after ethanol, nor by inhibition of hepatic AldDH activity in either strain.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaldehyde↗

PubMed1984

Effects of vanadate on intracellular reduction equivalents in mouse liver and the fate of vanadium in plasma, erythrocytes and liver.

Intraperitoneal injection of 180 mumol sodium vanadate/kg body wt in mice inhibits the in vivo metabolism of drugs by the hepatic monooxygenase, as measured by exhalation of 14CO2 after treatment with appropriately labeled [14C]methacetin. Determinations of hepatic GSH, NADPH and NADH after vanadate injection show an initial and transient decrease of GSH (10 min, 20%), followed by a transient decrease of NADPH (30 min, 23%), followed by a decrease of NADH (40 min, 23% and 60 min, 26%). Rat liver organ spectrophotometry in the dual-wavelength mode shows an immediate response of the NAD(P)H level, which decreases transiently after addition of vanadate. Furthermore, EPR and AAS measurements indicate that vanadium occurs in the plasma in the oxidation states +IV and +V, whereas in intracellular compartments in liver and erythrocytes vanadium exists practically only in the +IV form (vanadyl). The duration of the inhibition for about 2 h coincides well with the transient concentration of vanadate in plasma, which decreases more rapidly than vanadyl. Maximal drug inhibition is associated with the phase of rapid formation of vanadyl in the liver. The experiments are in accordance with the hypothesis that vanadate inhibits the cytochrome P-450 dependent oxidative drug metabolism by diversion of reducing equivalents away from cytochrome P-450. Further evidence for such a hypothesis is provided by in vitro experiments in microsomes. Vanadate causes a dose dependent decrease of ethoxyresorufin deethylation which is reversible by the addition of NADPH.

Acetamides↗

PubMed1984

Biological similarities and differences between rats genetically different in alcohol preference.

This paper is an inventory of some behavioural, biochemical and pharmacological similarities and differences between two inbred strains of Wistar rats differing in voluntary consumption of ethanol, namely: UChA and UChB with low and high preferences respectively for ethanol under conditions involving free choice between a 10% (v/v) ethanol solution and distilled water. The following strain differences were observed: ethanol consumption (UChA less than UChB); total water consumption (UChA less than UChB); solid food consumption (UChA greater than UChB); rate of recovery of ethanol label in expired CO2 (UChA less than UChB); oxidation of ethanol to acetaldehyde by brain homogenates (UChA greater than UChB); acetaldehyde disposal by brain homogenates (UChA less than UChB); ethanol (90 mmol/kg, i.p.) sleeping-time (UChA less than UChB); chronic and acute tolerance to ethanol (UChA developed it, whereas UChB did not); lethal doses of ethanol (UChA greater than UChB); recovery rate of the label of gluconate in expired CO2 (UChA less than UChB); recovery rate of the label of fructose in expired CO2 (UChA less than UChB); blood-glucose level after glucose (1 g/kg, i.p.) load (UChA less than UChB). No strain differences were observed in the rate of recovery in expired CO2 of the label of the following substrates: acetate, pyruvate, butyrate, citrate, ribose, glycerol, sorbitol, glucose and galactose.

Alcoholic Intoxication↗

PubMed1981

Genetic differences in tolerance to ethanol: a study in UChA and UChB rats.

The development of tolerance to ethanol was studied in two strains of rats, UChA (low ethanol consumer) and UChB (high ethanol consumer), by the sleeping time test. Marked tolerance (perhaps both metabolic and tissue) appeared in UChA rats, while only a slight tissue tolerance and not a metabolic one appeared in the UChB rats, when they were offered 10% ethanol as the sole fluid during 31 days (p less than 0.001). In UChA, but not in the UChB rats, the chronic treatment with ethanol induced tolerance to pentobarbital as shown by the same test.

Alcoholism↗

PubMedDate not supplied

Effect of different treatment regimens with ethanol and p-chlorophenylalanine on tolerance development in UChA and UChB rats.

Since we have previously observed a genetic difference in the development of tolerance to the narcotic effect of ethanol in UChA and UChB rats when providing them with a 10% v/v ethanol solution as sole drinking fluid, experiments were performed in order to know whether the resistance to development of tolerance to ethanol in UChB rats was also exhibited after other regimens of ethanol administration, namely, a 2.76 g/kg ethanol IP injection 24 hr before the experiment, only 10% v/v ethanol solution as sole drinking fluid for 21 days, or receiving acutely a daily dose of 2.76 g/kg ethanol by gavage for seven days. Participation of serotoninergic neurons was tested by treating rats with p-chlorophenylalanine (p-CPA), a known serotonin depletor. Results show that UChA rats developed tolerance to ethanol-induced narcosis and hypothermia, while UChB rats developed it to narcosis only when they received acute oral doses of ethanol for 7 days and did not develop tolerance to hypothermia with any of the treatment regimens. p-CPA pretreatment did prevent the development of tolerance in both strains of rats, confirming the participation of serotoninergic neurons in ethanol tolerance in rats.

Animals↗

PubMedDate not supplied

Effect of 3-amino-1,2,4-triazole on narcosis time and lethality of ethanol in UChA rats.

The capacity of rat brain homogenates to oxidize ethanol by catalase peroxidative system, previously reported, was reevaluated in experiments using lower ethanol concentration, showing that the effect of this system can be observed even with a concentration of 50 mM, equivalent to non lethal blood level. The involvement of catalase was confirmed by its blocking by aminotriazole (AT) or methanol but not by pyrazole or butanol. Evidence for a functional role of ethanol oxidation by brain catalase in the action of this substance was given by the fact that rats pretreated with AT (1 g/kg IP) exhibited a significant shorter narcosis than untreated controls, strongly suggesting the mediation of acetaldehyde in this effect. Previous results with doses of 60 mmole/kg IP were confirmed with 70 mmole/kg IP, but not with 90 mmole/kg IP. A significant prolonging of narcosis time was observed when AT was administered after any of these doses by an unknown mechanism. Furthermore it was observed that AT pretreatment reduced significantly the lethal effect of 110 mmole/kg IP ethanol; but when AT was given after ethanol (90 mmole/kg IP) it enhanced the lethality. These results suggest that catalase peroxidative pathway might play a role not only in narcosis time but also in ethanol toxicity.

Amitrole↗

PubMedDate not supplied

The effects of alpha-methyl-p-tyrosine pretreatment on ethanol-induced narcosis and hypothermia, as well as in the development of tolerance to these effects in UChA and UChB rats.

We have previously reported that UChA rats (genetically low ethanol consumer) develop tolerance to narcosis time easier than UChB rats (genetically high ethanol consumer). We also have reported that UChA rats develop tolerance to the hypothermic effect of ethanol, while in UChB rats the repeated administration of ethanol induces sensitization towards this effect. In the present paper the effects of alpha-methyl-p-tyrosine (AMPT)--a competitive inhibitor of norepinephrine synthesis--on ethanol-induced narcosis and hypothermia, as well as in the development of tolerance to these effects, were studied in both strains of rats. Results obtained show that AMPT pretreatment induced a significantly higher increase in narcosis time and hypothermia, as well as, greater susceptibility to ethanol toxicity in UChB than UChA rats. Furthermore, the simultaneous treatment with AMPT and ethanol did not change the development of tolerance to narcosis time in both strains and to hypothermia and sensitization in UChA and UChB rats respectively.

Alcohol Drinking↗

PubMedDate not supplied

Effect of 3-amino-1,2,4-triazole on the hypothermic effect of ethanol and on ethanol tolerance development.

The effect of aminotriazole (AT), inhibitor of catalase activity, on hypothermia and narcosis induced by ethanol and on the acquisition of tolerance to the ethanol hypothermic and narcotic effect was studied. Rats were pretreated with AT (1 g/kg IP) 1 hour before the test dose of ethanol (2.76 g/kg IP) and narcosis time, hypothermia and ethanol blood levels evaluated (first test). For studies on tolerance to ethanol, rats of the first test received daily (for 7 days) a dose of AT (1 g/kg IP) 1 hour before ethanol (2.76 g/kg) given by gavage, and the same parameters evaluated (8th day test). Results were compared to similar groups of rats without AT pretreatment (controls, 1st and 8th day test). Rats pretreated with AT exhibited a shorter narcosis time induced by ethanol but this treatment did not alter the hypothermic effect of ethanol nor ethanol disposal rate. Chronic ethanol treatment induced tolerance to the narcotic and hypothermic effect of ethanol as well as a metabolic tolerance. AT administered daily before the dose of ethanol produced a partial blockade of the development of tolerance to the narcotic effect of ethanol, but did not alter the development of hypothermic or metabolic tolerance. The brain catalase system seems to play a role in narcosis and on the development of tolerance to this effect of ethanol, but not in the hypothermic effect or in the development of tolerance to this ethanol effect. Since the inhibition of liver catalase activity by AT treatment was not correlated with changes in ethanol disposal rate, the liver catalase system appears not to play a role in the metabolic tolerance.

Amitrole↗

PubMedDate not supplied

Ethanol intake: effect on liver and brain mitochondrial function and acetaldehyde oxidation.

The effect of a chronic ethanol consumption by forcing rats to drink a 20% v/v ethanol solution as sole drinking fluid, for 3 months, was evaluated on: liver and brain mitochondrial function, the capacity of isolated mitochondria to oxidize acetaldehyde, as well as on the low Km mitochondrial AlDH activity, in rats. The O2 uptake by liver and brain mitochondria in the presence of glutamate + malate, succinate or ascorbate + TMPD, was measured polarographically with a Clark electrode. Acetaldehyde oxidation was measured by the disappearance rate in presence of the intact or disrupted mitochondria (AlDH activity) by gas chromatography. Results indicate that an ethanol intake of 11 g/kg b.wt. per day produce a significant reduction of the liver mitochondrial respiration tested with all the substrates used, including acetaldehyde. In contrast, the activity of AlDH in disrupted mitochondria remained unchanged. These results are in accord with the idea that a progressive deterioration of liver mitochondrial function appears with the increase in amount of ethanol consumed, and that alterations of acetaldehyde oxidation by intact mitochondria can be detected before an alteration of the AlDH activity. Concerning the brain, this ethanol consumption regimen did not affect the brain mitochondrial respiration tested with glutamate + malate, succinate or ascorbate + TMPD, but it induces an increase in acetaldehyde oxidation rate by intact brain mitochondria. The imposed increase in the cerebral aldehyde oxidizing capacity could reflect a principal biochemical mechanism underlying neural adaptation to ethanol.

Acetaldehyde↗