Effects Of Ethanol Consumption Research Articles

Effects of ethanol consumption by adolescent alcohol-preferring P rats on subsequent behavioral performance in the cross-maze and slip funnel tests

Neonatal alcohol exposure during the first 1–2 weeks of age is known to produce subsequent behavioral hyperactivity in rats. However, little is known about the effects of alcohol exposure during adolescence on subsequent adult behavior. In the present study, male and female P rats had free access to 10% alcohol during adolescence (3–8 weeks of age). After 8 days of abstinence, their behavior was evaluated in the cross-maze and in the inescapable slip funnel tests during the 10th week of age. Two-way ANOVAs revealed significant effects of alcohol drinking on several variables. Compared to alcohol-naive rats, the alcohol-exposed group started exploration earlier (3.5 ± 0.3 vs. 5.4 ± 0.7 s, p = 0.03) and made fewer defecations. In the slip funnel test, the alcohol group spent more time immobile (130 ± 7 vs. 107 ± 5 s, p = 0.01) and less time attempting to escape out of the funnel (11 ± 2 vs. 28 ± 5 s, p = 0.002) than the control group. Overall, the results suggest that the effects of alcohol drinking by P rats during adolescence on subsequent behavior are to reduce novelty-induced anxiety (cross-maze test) and lower response to stress induced by an inescapable situation (slip-funnel test).

Effect of ethanol consumption on adult rat liver mitochondrial populations analyzed by flow cytometry.

In the present study, the effects of administering ethanol to adult male rats on the distribution of the low fluorescence population (LFP) and high fluorescence population (HFP), and the rhodamine-123 fluorescence intensity of these groups of mitochondria are analyzed by flow cytometry. Our results show that ethanol administration to adult male rats induces a redistribution of the HFP and LFP mitochondrial populations leading to an increase of the less functional HFP mitochondria. In addition, ethanol induced an increase in the mean intensity of green fluorescence of the HFP that is probably related to an increased number of rhodamine-123 binding sites per mitochondria resulting from mitochondria enlargement.

Differential Effects of Ethanol Consumption on Synthesis of Cytoplasmic and Mitochondrial Encoded Subunits of the ATP Synthase

The relative concentrations of several subunits of the mitochondrial F0.F1-ATP synthase were determined in mitochondria and submitochondrial particles prepared from the livers of ethanol-fed and control rats. The polypeptides were separated by sodium dodecylsulfate-polyacrylamide gel electrophoresis and the stained gels were analyzed by densitometry for the relative concentrations of the ATP synthase subunits. A significant decrease in the relative concentration of the mitochondrial gene product, ATPase subunit 8, was observed in mitochondria and submitochondrial particles from ethanol-fed animals. The relative concentration of the other mitochondrial encoded ATPase subunit, ATPase 6, was also depressed, as confirmed in submitochondrial particles. In contrast, there were no significant ethanol-related depressions in subunits alpha, beta, and OSCP of the F0.F1 or the adenine nucleotide carrier in intact mitochondria. These results demonstrate that ethanol consumption causes a decrease in the content of mitochondrial synthesized subunits 6 and 8 whereas no effect is exerted on the concentrations of nuclear gene products of the ATP synthase complex. Likewise, the adenine nucleotide transporter, also a nuclear gene product, is unaffected by ethanol consumption.

Effects of Ethanol Consumption on Enriched Natural Killer Cells from C57BL/6 Mice

Ethanol (20% w/v) given to female, C57BL/6 mice in their drinking water was previously shown to suppress natural killer (NK) cell cytolytic activity in a mixed splenocyte population. The present study was designed to examine the hypothesis that ethanol consumption independently results in inhibition of NK cell cytolytic activity. Mice were given 20% w/v ethanol in the drinking water for 2 weeks, and splenic NK cells were enriched up to 88% based on surface expression of NK1.1. Cytolytic activity of these freshly enriched NK cells from ethanol-consuming mice against YAC-1 lymphoma cells was inhibited an average of 41% relative to water-drinking controls. Cytolytic activity of enriched NK cells from ethanol-consuming mice was stimulated to levels equal to control water-drinking mice after 16- to 18-hr incubation in 1000 units/ml recombinant interleukin 2. These data indicate that in vitro cytolytic activity of NK cells from ethanol-consuming mice is inhibited in the absence of other modulatory leukocytes.

Bidirectional changes in striatal D1-dopamine receptor density during chronic ethanol intake

Results of previous studies on the effects of ethanol consumption on the properties of D1 dopamine receptors appear contradictory and inconclusive. In this study we have examined the time course of the effects of dietary ethanol on the properties of striatal D1 dopamine receptors. Chronic ethanol intake led to bidirectional changes in the maximum number (Bmax) of [ 3H]SCH-23390 binding to striatal D1 dopamine receptors measured 10 hrs after termination of the ethanol intake. A significant decrease (80% of control), increase (159% of control), increase (122% of control), and decrease (85% of control) after 1, 2, 3, and 4 weeks of ethanol intake respectively was observed. The bidirectional changes disappeared after 6 and 10 weeks of continued ethanol intake and the Bmax returned back to the control level. The receptor affinity (Kd), however, remained unaltered in all cases. These data suggest that the duration of ethanol exposure may be an important determinant in regulating D1 dopamine receptor density.

The effect of chronic ethanol intake on brain NGF level and on NGF-target tissues of adult mice

The effect of ethanol consumption on the forebrain and hypothalamus of adult mice was investigated. A consistent decrease of biological activity and of nerve growth factor (NGF) immunoreactivity was observed in the hippocampus and hypothalamus of alcohol-treated mice. Biochemical studies also indicate that chronic ethanol intake causes a reduction in the level of cholineacetyltransferase in the septum, hippocampus and striatum, but not in the cortex and other brain regions. This study provides evidence that long-term ethanol intake causes impairment of brain NGF level and of the cholinergic enzyme, regulated by NGF, suggesting that NGF synthesis and/or biological activity is affected in alcohol-related brain neuropathology.

Milk, lactose and ethanol as dietary factors in cataractogenesis in Guatemala. A case-control study

We performed a case-control study in 46 Guatemalan adults aged 26 to 79 years with a recent history of cataract extraction and 46 controls matched for sex, age (±5 years), and altitude of residence (±400m). The aetiological variables studied included: (i) effect of lactose digesting capacity as reflected by chance in breath hydrogen concentration; (ii) effect of the tolerance to a 240 ml challenge of milk containing 12 g of lactose; (iii) effect of usual lactose consumption; and (iv) effect of ethanol consumption. Adjusted relative risks, calculated using the matched-pair method, were 4.2 for a history of milk consumption, and 16.0 for a history of ethanol use. Non-suggestive associations were found for the milk tolerance challenge test and for lactose digesting capacity according to breath hydrogen concentration. We concluded that, in a Guatemalan population, ethanol is a more important risk factor than milk exposure, but both can influence cataract risk.

Effect of ethanol consumption during pregnancy on folate coenzyme distribution in fetal, maternal, and placental tissues

Ethanol has been shown to be a teratogen in humans and experimental animals; however, the mechanism of its actions is not known. Because ethanol interferes with the metabolism of folate coenzymes that participate in various biosynthetic pathways of nucleic acids, the effect of gestational ethanol consumption on the distribution of folate coenzymes in tissues was investigated with an eye to the possibility that such effects might shed light on the mechanism by which ethanol produces its teratogenic effect. Sprague-Dawley rats were fed a 35% ethanol-calorie liquid diet from gestation days 7–21; controls were pair-fed with isocaloric sucrose substituted for ethanol. Rats were killed on day 21. Food intake, maternal weight gain, litter size, and conceptus weight were similar between ethanol and control rats. However, fetal weight was decreased and placental weight increased in ethanol group as compared with the control. Total folates and folate coenzymes were determined in fetal liver and brain, placenta, and maternal liver. Ethanol consumption decreased 5-methyltetrahydrofolate in the placenta, which was compensated by increasing tetrahydrofolate and formyltetrahydrofolates. In fetal liver, formyltetrahydrofolates and formiminotetrahydrofolate were decreased and tetrahydrofolate increased with ethanol. In fetal brain, ethanol not only decreased total folates but also altered the coenzyme pattern by decreasing 5-methyltetrahydrofolate and increasing tetrahydrofolate and formyltetrahydrofolates. These changes in folate coenzyme pattern indicate ethanol-induced alteration in folate metabolism. The possible physiologic significance of these changes in relation to Fetal Alcohol Syndrome is discussed.

Effects of ethanol consumption during pregnancy and lactation on the outcome and postnatal growth of the offspring.

Although information about the pregnancy outcome of alcoholic mothers is relatively abundant, no information is available about the effects of ethanol consumption on the infant's postnatal growth. This investigation aims to describe the physical growth of 32 infants born to mothers accustomed to drinking pulque, a mild alcoholic beverage, on a daily basis during pregnancy and lactation and to quantitate the ethanol disposed through the milk, as well as to identify cases of newborns with fetal alcohol syndrome. No full-blown cases of the syndrome were found: birth weight was similar to their non-drinking counterpart, but the relative risk of newborns to drinking mothers to have a low birth weight was 3.39. Ethanol found in milk accounted for 40 mg/day available to the infant. The postnatal growth of infants of ethanol drinkers was similar to that of controls. Further studies on their mental development are required in order to understand the extent of the effects of such a habit.

Effect of Ethanol Consumption on Metabolism of S-Adenosyl-L-Methionine in Rat Liver

The effect of dietary alcohol and protein intake on hepatic levels of S-adenosyl-L-methionine (SAMe), S-adenosylhomocysteine, SAMe synthetase, and phosphatidylethanolamine-N-methyltransferase (PEMT) was investigated in rats receiving the following diets for 28 days: 20% protein (group I); 20% protein plus 5% ethanol (group II); 8% protein (group III); and 8% protein plus 5% ethanol (group IV). The daily food intake of rats did not differ significantly between groups, but the gain in bodyweight in groups III and IV was significantly less than in group I — the control group. The mean hepatic SAMe level in rats in group IV was significantly lower (46% below normal; p < 0.02) than in the control group, although SAMe synthetase activity was essentially unchanged in all groups. PEMT activity was less than the mean for the control group in 5 of 8 group IV animals. These data indicate that the hepatic content of SAMe is sensitive to even a low intake of ethanol, with potential adverse effects on vital methyltransferase reactions utilising SAMe as a methyl donor.

Effect of ethanol consumption and vitamin E supplementation on in vivo lipid peroxidation in rats

This study investigated the effects of short and long term vitamin E supplementation on ethanol induced lipid peroxidation in rats. Groups of rats were fed liquid diets in which ethanol provided 36% of the total calories (v/v) for 28 days or 18 months. The 28-day fed rats received supplemental alpha tocopherol 142 IU/kg of diet while those fed ethanol for 18 months were injected i.p. with 528 IU alpha tocopherol/kg body weight/day for 2 days prior to termination. At the end of the feeding period, ethane exhalation, conjugated dienes and lipid fluorescence were estimated as indices of free radical mediated products. Rats fed the ethanol diets for 28 days and 18 months exhaled more ethane than pair-fed controls. Increases in conjugated dienes and lipid fluorescence were observed in both the 28 day and 18 month groups of alcohol fed rats (p<0.05). Supplementation of the ethanolic diet with alpha tocopherol in the 28 day fed rats reduced conjugated dienes and lipid fluorescence (p<0.05) to values similar to controls; and also reduced ethane exhalation to near control levels (p<0.05). Rats fed ethanol for 18 months and given i.p. vitamin E injections showed reduced ethane exhalation but no reduction in the accumulative indices (lipid fluorescence) of lipid peroxidation. Thus, vitamin E act by reducing on-going in vivo lipid peroxidation thus preventing the accumulation of lipid peroxide products. In the present study, vitamin E probably acted as a free radical scavenger in retarding alcoholic liver damage.

Effects of ethanol consumption on bioactivation and hepatotoxicity of N-nitrosodimethylamine in rats

To study the effects of ethanol on the hepatotoxicity of N-nitrosodimethylamine (NDMA), 5 mg NDMA/kg body weight was injected intraperitoneally 3 times a week for 6 weeks into rats pairfed liquid diets containing 36% of energy either as ethanol or as additional carbohydrates. Another group of rats was pair-fed with the same diets but injected with saline instead of NDMA. Co-administration of ethanol and NDMA produced much higher elevations of serum alanine and aspartate aminotransferase and glutamic dehydrogenase activities than the administration of either agent alone. The combined treatment also slightly increased focal necrosis, whereas other liver lesions (steatosis and fibrosis) and the functional impairment of mitochondrial respiration were not affected significantly. Microsomal low K m NDMA demethylation, as well as NDMA denitrosation, were inhibited markedly by incubation with an antibody against P450IIE1, suggesting the involvement of this alcohol-inducible P450 in both NDMA bioactivation reactions. The addition of ethanol inhibited P450-dependent demethylation and denitrosation of NDMA in liver microsomes, whereas both activities were enhanced markedly by chronic ethanol administration. At ethanol concentrations similar to those prevailing in the blood of alcohol-fed animals at the time of NDMA administration, hepatic microsomal demethylation and denitrosation remained significantly higher in ethanol-fed rats given NDMA than in controls. Our results suggest that bioactivation plays a critical role in the hepatotoxicity of NDMA and its aggravation by chronic alcohol consumption.

Effects of Ethanol and Low-Carbohydrate Diet on Contents of Noradrenalin, Dopamine, Serotonin and their Metabolites in Rat Brain.

Effects of ethanol consumption and intake of low-carbohydrate (low-CHO) diet on noradrenaline (NA), dopamine (DA) and its metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), serotonin (5HT) and its metabolite, 5-hydroxyindoleacetic acid (5HIAA) contents in six brain regions of rats were investigated. 1) Change of DA neuron Ethanol-containing control diet (hypercaloric ethanol diet) did not affect DA content in any area of brain, but decreased HVA in cortex and hypothalamus and increased DOPAC and HVA in midbrain. Low-CHO diet increased DA content in striatum, DOPAC and HVA in midbrain, but decreased DOPAC in hippocampus and hypothalamus, and HVA in cortex, pons and medulla, hippocampus and hypothalamus. Ethanol-containing low-CHO diet (isocaloric ethanol diet) increased DA level in striatum, DOPAC and HVA in midbrain, but decreased HVA in cortex, hippocampus, striatum and hypothalamus. These results suggest that i) hypercaloric ethanol diet has an opposite effect to carbohydrate on DA metabolism: hypercaloric ethanol diet and lowered carbohydrate intake per se enhance DA metabolism in midbrain, whereas inhibit it in cortex and hypothalamus, ii) lowered carbohydrate intake also declines DA metabolism in pons and medulla and hippocampus, whereas enhances DA synthesis in striatum, iii) the combined effect of ethanol and carbohydrate intake on DA metabolism is inhibited each other in the rats of isocaloric ethanol diet feeding, and this diet decreased DA metabolism in striatum. 2) Change of 5HT neuron Hypercaloric ethanol diet did not affect the contents of 5HT and 5HIAA in any region of brain.(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatic alcohol dehydrogenase activity in alcoholic subjects with and without liver disease.

Alcohol dehydrogenase activity was measured in samples of liver tissue from a group of alcoholic and non-alcoholic subjects to determine whether decreased liver alcohol dehydrogenase activity is a consequence of ethanol consumption or liver damage. The alcoholic patients were classified further into the following groups: control subjects with no liver disease (group 1), subjects with non-cirrhotic liver disease (group 2), and subjects with cirrhotic liver disease (group 3). The non-alcoholic subjects were also divided, using the same criteria, into groups 4, 5, and 6, respectively. The analysis of the results showed no significant differences when mean alcohol dehydrogenase activities of alcoholic and non-alcoholic patients with similar degrees of liver pathology were compared (groups 1 v 4, 2 v 5, and 3 v 6. Alcohol dehydrogenase activity was, however, severely reduced in patients with liver disease compared with control subjects. Our findings suggest that alcohol consumption does not modify hepatic alcohol dehydrogenase activity. The reduction in specific alcohol dehydrogenase activity in alcoholic liver disease is a consequence of liver damage.

Gestational Ethanol Consumption on Tissue Amino Acid Levels: Decreased Free Histidine and Tryptophan in Fetal Tissues with Concomitant Increase in Urinary Histamine Excretion

The effects of ethanol consumption during pregnancy on maternal, placental, and fetal tissue amino acid levels and metabolism were investigated. Pregnant Sprague-Dawley rats were given 35% ethanol-calorie liquid diet, ad libitum, from gestation day 7 to 21. Control rats were pair-fed with isocaloric sucrose substituted for ethanol. Ethanol consumption decreased fetal body weight and increased placental weight. Twenty-four amino acids were determined in six tissues (maternal plasma and liver, placenta, fetal plasma, liver, and brain) by HPLC with orthophthalaldehyde derivatization. The effects of ethanol on free amino acid levels differed from tissue to tissue. In general, ethanol affected more amino acids in maternal plasma, fetal plasma, and liver. Maternal liver, placenta, and fetal brain amino acids were more resistant to ethanol effect. Two essential amino acids, histidine and tryptophan, were consistently decreased in fetal tissues by maternal ethanol consumption. The values (ethanol vs. control, nmole/ml or g, mean +/- SEM, N = 20) of fetal plasma, liver, and brain for histidine were 51.8 +/- 6.0 vs. 85.3 +/- 4.5 (p = 0.001), 269.0 +/- 26.4 vs. 503.7 +/- 47.3 (p = 0.0004), and 117.9 +/- 7.7 vs. 154.6 +/- 8.7 (p = 0.0055), respectively; and for tryptophan were 105.7 +/- 3.1 vs. 132.2 +/- 4.1 (p = 0.0001), 128.8 +/- 3.7 vs. 144.3 +/- 6.0 (p = 0.0407), and 83.4 +/- 7.2 vs. 103.6 +/- 3.2 (p = 0.0198), respectively. Histidine was also decreased in placenta by ethanol (138.1 +/- 6.6 vs. 189.1 +/- 11.8 nmole/g, p = 0.0014).(ABSTRACT TRUNCATED AT 250 WORDS)

The Effects of Ethanol Consumption on the Expression of Immunity to Trichinella spiralis in Rats

The effects of ethanol ingestion on immune responses of female rats against Trichinella spiralis (T. spiralis) infections were investigated. Female rats were pair-fed either ethanol-containing or isocaloric control liquid diets for 68 days, during which time they underwent one pregnancy cycle. For some studies, animals were fed ethanol diets for 68 days beginning prior to pregnancy and continuing through lactation and involution. They were infected on Day 7 of involution with 1000 L1 larvae of T. spiralis and tested for a primary rejection response 10 days later. To test for a secondary immune response, rats were infected with T. spiralis, placed on ethanol-containing liquid diet 15 days later, and after 68 days on diets, challenged with 1000 T. spiralis larvae and killed 3 days later. For primary immunized studies, ethanol-treated animals demonstrated significantly lower levels of anti-T. spiralis serum antibodies in ELISA, reduced rates of H3 thymidine incorporation by lymph node cells stimulated with T. spiralis antigen and significantly higher numbers of intestinal worm burdens (decreased immunity) compared with pair-fed controls. For animals sensitized to T. spiralis prior to pregnancy and given a secondary challenge during involution, no differences were found between ethanol and pair-fed animals in their ability to reject their worm burdens or in anti-T. spiralis serum antibody levels; however, ethanol-treated animals showed reduced rates of thymidine incorporation by lymph node cells when stimulated with T. spiralis antigen.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetic Interaction Between Indoramin and Ethanol

1. The effect of ethanol consumption (0.5 g/kg) on the pharmacokinetics of the alpha adrenoceptor antagonist indoramin, administered orally (50 mg) or intravenously (0.175 mg/kg) has been investigated in young volunteers. Sedation was also assessed using a visual analogue scale. 2. After oral indoramin administration, ethanol caused increases of 58% (P less than 0.01) in Cpmax, and 25% (P less than 0.05) in AUC. There was no effect of alcohol on elimination half-life. The combination of ethanol and indoramin was more sedative than indoramin alone. 3. Ethanol did not alter the pharmacokinetics of an intravenous dose of indoramin. However indoramin caused a small but statistically significant increase (26%) in blood ethanol concentrations during the first 1.25 h after dosing. Both indoramin and ethanol caused sedation. 4. The increased bioavailability of oral indoramin in the presence of ethanol may reflect some enhanced absorption, but it is also consistent with inhibition of first-pass metabolism of a flow-limited drug. The clinical implications are discussed.

Effects of ethanol consumption on the morphology of the rat seminiferous epithelium.

The effects of ethanol consumption on the morphology of the seminiferous epithelium, with particular emphasis on Sertoli cell ultrastructure, were examined during and following pubertal development. Sprague-Dawley rats were maintained on chronically high levels of ethanol for 7 weeks beginning at 29 days of age. Animals in Group 1 were fed a liquid diet containing ethanol (36% ethanol-derived calories) ad libitum. Group 2 animals were paired with animals in Group 1 and fed a liquid control diet in the amount consumed by their ethanol partners (g/kg body wt/day). Animals in Group 3 were fed Purina rodent chow ad libitum. Blood samples were collected at 60 days for determination of plasma testosterone levels. On day 79, each epididymis, the adrenals and the right testis were removed from anesthetized animals and weighed; the left testis was removed and processed for light and electron microscopy. Blood alcohol levels were consistently high throughout the feeding period, averaging 272.6 +/- 9.7 mg/100 ml at 1900 hours (1 hour after lights off) and 178.8 +/- 20.8 mg/100 ml at 1330 hours. Testosterone levels were lower in ethanol-consuming animals than in pair-fed or control subjects. Testis weight was also somewhat reduced in ethanol-consuming animals; however, when adjusted for body weight, relative testis weights were found to be increased in ethanol and pair-fed animals. Epididymal weights were reduced in both ethanol and pair-fed animals. Relative adrenal weights were increased by ethanol. The most dramatic effect of ethanol consumption was on the morphology of the seminiferous tubules.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of high-protein diets on brain phospholipid, ganglioside and monogalactosyl glycolipid content previously altered by long-term low-protein and ethanol administration.

A previous study was undertaken to determine the influence of the combined effects of ethanol consumption and a low-protein diet on brain membrane (phospholipids and gangliosides) and myelin (monogalactosyl glycolipids) lipids. Male Wistar rats chronically consuming ethanol were fed isoenergetic diets containing 22% protein (controls) or 6% protein (protein-deprived) from 60 to 240 days of age. Protein malnutrition initiated at 60 days of age affected phosphatidylglycerol, sphingophospholipid, monosialoganglioside GM1 and cerebroside containing nervonic fatty acid by 240 days of age. Among the effects of ethanol was an increase of the relative proportion of lipid galactose in monogalactosyl glycolipids and of N-acetylneuraminic acid in the trisialoganglioside GT1b, while there was decrease of the lipid phosphorus in the investigated phospholipids and of the disialoganglioside GD1a. The low-protein diet generally interfered with ethanol effects except for monosialo GM3, GM2 and GM1 gangliosides. The present study was carried out to investigate whether the ethanol-induced effect on these brain lipids could be elevated when we switched these animals to diets with 21 or 34% protein during the following 90 days. It was found that increasing protein intake and cessation of drinking ethanol returned the investigated brain phospholipids, monogalactosyl glycolipids and gangliosides to control values.

Protein turnover in subcellular fractions of brain from the ethanol-fed rat

The effect of ethanol consumption (27% of energy intake) for 21 days, on protein synthesis and degradation in subcellular fractions of rat brain was investigated using the Na 2 14CO 3 labelling procedure. Ethanol administration elicited an increase in the rate of protein synthesis in all fractions which was accompanied by an increase of similar magnitude in the rate of breakdown. These results imply that whilst ethanol increases the rate of protein turnover it is without effect on the rate of protein accretion.