Interaction of ethanol with beta-carotene: delayed blood clearance and enhanced hepatotoxicity.

Because we had found that ethanol interacts with retinol, we investigated whether it also affects its precursor, beta-carotene. In 14 baboons fed ethanol (50% of total energy) for 2 to 5 yr with a standard amount of beta-carotene (one 200-gm carrot/day), levels of beta-carotene were much higher than in controls fed isocaloric carbohydrate, both in plasma (122.5 +/- 30.9 nmol/dl vs. 6.3 +/- 1.4 nmol/dl; p less than 0.005) and in liver (7.9 +/- 1.1 nmol/gm vs. 1.8 +/- 0.5 nmol/gm; p less than 0.001). Even 20 days after withdrawal of the carrots, plasma beta-carotene levels remained higher in alcohol-fed baboons than in controls (10.1 +/- 3.8 nmol/dl vs. less than 0.1 nmol/dl). Next, the diet was supplemented with beta-carotene beadlets: in four pairs of baboons given a low dose of beta-carotene (3 mg/1,000 kcal), plasma levels were significantly higher in alcohol-fed animals than in controls, even when expressed per cholesterol (although the latter increased with alcohol intake). Seven pairs of animals were given a higher dose (30 mg/1,000 kcal) of beta-carotene for 1 mo, followed, in four pairs, by 45 mg for another month. On cessation of beta-carotene treatment, plasma levels decreased more slowly in the alcohol-fed baboons than in the controls. Percutaneous liver biopsy specimens revealed that liver concentrations of beta-carotene correlated with plasma levels but were higher in the alcohol-fed baboons than in the control baboons, whereas the beta-carotene-induced increase in liver retinoids was lower (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)     

Cytotoxicity of mononuclear cells and vulnerability of hepatocytes in alcoholic fatty liver of baboons

ABSTRACT— Mononuclear cell cytotoxicity against autologous, allogeneic and xenogeneic (rabbit) hepatocytes was investigated in nine baboons fed alcohol for 17–21 months and in nine pair-fed controls. All alcohol-fed animals developed fatty liver. Cytotoxicity of mononuclear cells was not observed when rabbit hepatocytes were used as target cells, but mononuclear cells of alcohol-fed baboons were cytotoxic against hepatocytes of both control animals and hepatocytes from alcohol-fed baboons, including the animals' own hepatocytes. Increased vulnerability of hepatocytes of alcohol-fed baboons was also demonstrated since mononuclear cells of both controls and alcohol-fed animals were more cytotoxic against hepatocytes of alcohol-fed baboons than against those of controls. Thus, autologous and heterologous hepatocytes are more sensitive in the baboon than rabbit hepatocytes in demonstrating cytotoxicity already at the stage of fatty liver. Two factors are contributory: mononuclear cells cytotoxicity and vulnerability of hepatocytes.     

Effects of Ethanol on Intestinal Absorption of Drugs.

The effect of chronic alcohol intake on the intestinal absorption of seven compounds belonging to a homologous series (ciprofloxacin derivatives) was evaluated using an in situ rat gut technique that measures the intrinsic absorption rates of the compounds both in control and chronic alcohol-fed rats. For chronic alcohol treatment, the animals were fed a liquid diet containing ethanol (36% of calories), whereas an isocaloric diet was given to the pair-fed control animals. The biophysical absorption model, relating the intestinal absorption rate constants and partition indexes of the tested compounds, was then established either for control or alcohol-fed animals. Differences were analyzed and tentatively interpreted on the basis of general diffusion principles. Results revealed that, in chronic alcohol-fed animals, hydrophilic homologs are absorbed at a significantly faster rate than in control ones, whereas lipophilic homologs do not change their absorption rate relative to controls. Results demonstrate that the bulk polarity of the microvillous lipoidal membrane is enhanced by chronic ethanol intake, whereas basic features of the aqueous boundary layer are not altered. These observations suggest that the physicochemical properties of the compounds are an important factor in explaining the influence of chronic alcohol intake on passive intestinal absorption of xenobiotics. The possible practical implications of our results are discussed from a speculative viewpoint     

Free Radical Formation in Livers of Rats Treated Acutely and Chronically with Alcohol

The spin trapping method was used to assess formation of free radical intermediates in vivo before and after acute alcohol administration to rats. Ascorbyi radicals and spin adducts of dietary alcohol or endogenous compounds, such as lipids, were detected with higher frequency in bile from alcohol-fed rats than in corresponding samples from rats fed control diets. When alcohol was given acutely to these animals, the 1-hydroxyethyl radical metabolite of ethanol was also formed at higher rates in livers of rats that had been fed ethanol chronically. Furthermore, formation of lipid radicals was enhanced after acute alcohol administration. These data support the hypothesis that chronic alcohol administration causes development of oxi-dative conditions in the liver, which subsequently lead to formation of differing types of radicals. Liver microsomes from alcohol-fed rats also metabolized ethanol to the 1-hydroxyethyl radical at higher rates than controls.     

Gender differences in blood levels, but not brain levels, of ethanol in rats

Female rodents tend to drink more alcohol than males, a difference that emerges at puberty and appears to vary over the female estrous cycle. In addition, male and female rodents display different responses to alcohol; for example, female rats are reported to have faster elimination rates than males. We were interested in whether circulating ovarian hormones influence alcohol distribution to or elimination from the brain of rats, which might explain observed differences in drinking behavior. We administered 0.8 g/kg of ethanol via intraperitoneal injection to age-matched male and female Sprague-Dawley rats. Extracellular brain ethanol was sampled using microdialysis, and vascular ethanol concentrations were determined via tail blood collection, in two separate experiments. Ethanol pharmacokinetic parameters were calculated for both compartments. There were no differences in pharmacokinetic parameters due to gender or estrous cycle stage in brain ethanol concentration profiles. There were, however, differences in blood ethanol profiles: females showed faster elimination rates and a smaller area under the ethanol concentration versus time curve than males. In addition, the maximum concentration varied significantly across the estrous cycle. These results suggest that (1) circulating ovarian hormones do not influence alcohol distribution to the brain, but do influence distribution to more peripheral tissues such as the tail; and (2) apparent differences in tail blood alcohol levels may not reflect differences in brain levels.     

More Rapid Elimination of Alcohol in Women as Compared to Their Male Siblings

Sex differences in rates of ethanol elimination were investigated in natural siblings to reduce genetic variability as compared to subjects chosen at random. Ethanol was infused intravenously in a dose of 0.6 g/kg of body weight over 45 to 60 min and serial blood samples obtained for 5 hr. The mean rate of ethanol elimination was higher in seven women, not different in one, and lower in one compared with their male siblings. The mean rate of ethanol elimination for all nine women was higher at 1.93 +/- 0.12 as compared with the value of 1.69 +/- 0.17 mmoles/kg body weight/hr in the men (p less than 0.05). Higher rates of ethanol metabolism in women as compared to men may be important in the increased susceptibility of women to liver injury caused by alcohol consumption.     

Alcohol Consumption by Young Actively Growing Rats: A Study of Cortical Bone Histomorphometry and Mechanical Properties

Alcohol consumption by young actively growing rats has been previously demonstrated to decrease cortical and cancellous bone density, to reduce trabecular bone volume, and to inhibit bone growth at the epiphyseal growth plate. This study addresses the action of alcohol on cortical bone growth using histomorphometric techniques and on mechanical properties by three-point bending. Four-week-old, female Sprague-Dawley rats were divided into three groups. Alcohol-treated animals were fed a modified Lieber-DeCarli diet ad libitum containing 35% ethanol-derived calories, whereas the pairfed animals (weight-matched to ethanol rats) received an isocaloric liquid diet in which maltose-dextrin-substituted calories were supplied by ethanol. Chow animals were fed a standard rat chow ad libitum. Femora were removed for analysis after 2, 4, 6, or 8 weeks on the diets. Cortical bone area, bone formation rates, and mineral apposition rates were reduced in the alcohol-fed animals. Bone stiffness, strength, and energy absorbed to fracture were significantly lower in the alcohol-fed animals. This distinctive alcohol effect was revealed to be caused by lower quality bone tissue as reflected by lower elastic moduli and yield strengths.     

Selective Fetal Malnutrition: Effect of Acute and Chronic Ethanol Exposure upon Rat Placental Na, K-ATPase Activity

Intrauterine growth retardation (IUGR) is characteristic of the fetal alcohol syndrome (FAS). This IUGR is partly due to the toxic effect of ethanol upon placental function, including amino acid transport. Amino acid transport is dependent, in part, upon Na,K-ATPase; therefore, plasma membrane activity of Na,K-ATPase was measured in rat placentas following acute or chronic ethanol exposure. Acute (A) animals were chow fed and gavaged with ethanol on day 20 of gestation and killed 2 hr later; controls (A-C) received sucrose. Binge (B) animals were gavaged on gestation days 18 and 19; controls (B-C) received sucrose. Chronic animals were fed ethanol in a liquid diet containing 2% (CHR-2%) or 6% (CHR-6%) ethanol by volume and killed on day 20. Controls (CHR-2%-C or CHR-6%-C) were isocalorically pair fed. Maternal blood ethanol levels were 197.1 +/- 29.7 mg/dl (mean +/- SE) for A dams and 128.2 +/- 15.2 for B (drawn at time of death); 12.6 +/- 2.2 for CHR-2% and 195.0 +/- 26.0 for CHR-6% (drawn weekly and at time of death). Placental weight was increased and fetal weight decreased in the CHR-6% animals. A, B, and CHR-2% placental and fetal weights were unaffected. Na,K-ATPase specific activity was increased in B placentas: B = 134.7 +/- 16.5 versus B-C = 50.0 +/- 7.4 nmol of Pi/mg of protein/min (p less than 0.01). Conversely, CHR-6% treatment diminished enzyme activity: CHR-6% = 37.0 +/- 4.5 versus CHR-6%-C = 58.5 +/- 4.4 (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

In vivo hepatic energy metabolism during the progression of alcoholic liver disease: a noninvasive 31P nuclear magnetic resonance study in rats

We investigated serially in vivo the ratios of phosphorylated metabolites and the intracellular pH in the livers of rats fed ethanol chronically to evaluate the relation between changes in energy metabolism and the progression of alcoholic liver disease with 31P nuclear magnetic resonance spectroscopy. 31P nuclear magnetic resonance spectra of the liver were acquired noninvasively from rats pair-fed a nutritionally adequate liquid diet containing ethanol or an isocaloric amount of dextrose with an implanted intragastric cannula for up to 24 wk. A high blood alcohol level was constantly maintained. The spectra were obtained using a surface coil combined with a ferrite screen to eliminate nuclear magnetic resonance signals derived from the superficial muscles. Contaminating 31P nuclear magnetic resonance signals arising from abdominal tissues other than the liver were eliminated from the spectra by digital subtraction. Throughout the study the inorganic phosphate/beta-ATP peak area ratio observed in alcohol-fed rats was found to be consistently elevated in comparison with the control rats (at 3 to 5 wk alcohol-fed rats = 1.20 +/- 0.10, control rats = 0.78 +/- 0.04, p less than 0.05.; at 22 to 24 wk alcohol-fed rats = 1.23 +/- 0.10, control rats = 0.81 +/- 0.06, p less than 0.05.; mean +/- S.E.). The phosphomonoesters/beta-ATP ratio tended to be higher in alcohol-fed rats when compared with control rats. The intracellular pH measured by the chemical shift of the inorganic phosphate peak showed no significant differences between alcohol-fed rats and control rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chronic ethanol-induced myocardial protection requires activation of mitochondrial K(ATP) channels

Moderate alcohol consumption protects against coronary heart disease by unclear mechanisms. We tested whether chronic ethanol preconditioning requires activation of mitochondrial K(ATP)channels. Rats were fed 18% (v/v) ethanol in drinking water for 10 months. Blood alcohol levels at sacrifice were 3 mmol/l (0.015 gram percent). Isolated crystalloid-perfused hearts were subjected to global ischemia and reperfusion on a modified Langendorff apparatus. Prior alcohol exposure doubled the recovery of LVDP during reperfusion (45+/-5%v 20+/-3% of baseline for controls, n=6, P<0.01) and blunted the rise in LVEDP (3.5+/-0.5 v 5.5+/-0.4 times baseline for controls, n=6, P<0.01). Ethanol feeding also reduced creatine kinase release during reperfusion. Inhibition of mitochondrial K(ATP)channels with 5-hydroxydecanoate had no effect on baseline LVDP, LVEDP, or coronary flow but abolished the beneficial effects of alcohol on LV contractile recovery and myocyte necrosis. We conclude that mitochondrial K(ATP)channel activity is required for chronic ethanol-induced protection.     

Metadoxine in acute alcohol intoxication: a double-blind, randomized, placebo-controlled study

BACKGROUND: At present there are only intriguing and preliminary clinical results regarding the efficacy of metadoxine (pyridoxol L-2-pyrrolidone-5-carboxylate) in acute alcohol intoxication. The present study was planned with the aim of investigating the effectiveness of metadoxine in the management of patients affected by acute ethanol intoxication. METHODS: A double-blind, randomized, multicenter, placebo-controlled trial was carried out on 58 patients of both sexes with acute ethanol intoxication. Patients were treated with a single dose of 900-mg intravenous metadoxine (n = 29) or with placebo (n = 29). Patients were clinically and biochemically evaluated at 0.5, 1, 2, 3, 6, 9, and 12 hr after treatment. RESULTS: Treatment with metadoxine significantly decreased the half-life of ethanol in blood (from 6.70 +/- 1.84 to 5.41 +/- 1.99 hr; p < 0.013) and showed a faster rate of ethanol elimination. The effects on ethanol half-life in blood were accompanied by a faster onset of recovery from intoxication, defined as the time of the transition of blood ethanol levels to the immediately lower range defined by intoxication categories (in g/liter: 0 to 0.5, absent; 0.51 to 1.0, mild; 1.1 to 2.5, moderate; >2.5, severe). Thus the median time to onset of recovery was 0.95 hr with metadoxine and 2.34 hr with placebo (p = 0.013). The effects of treatment on blood alcohol levels were paralleled by a significant decrease in the rating of the toxic clinical symptomatology. At 2 hr the improvement of toxic symptoms (in percent of maximum possible) was 68 +/- 28 vs. 44 +/- 27% in controls (p < 0.002). CONCLUSIONS: In patients with acute ethanol intoxication metadoxine accelerated the elimination of ethanol from blood, which led to faster recovery from intoxication, and improved the behavioral toxic symptomatology. Metadoxine could be helpful in the management of acute ethanol intoxication.     

S-adenosyl-L-methionine attenuates alcohol-induced liver injury in the baboon

Chronic ethanol consumption by baboons (50% of energy from a liquid diet) for 18 to 36 mo resulted in significant depletion of hepatic S-adenosyl-L-methionine concentration: 74.6 +/- 2.4 nmol/gm vs. 108.9 +/- 8.2 nmol/gm liver in controls (p less than 0.005). The depletion was corrected with S-adenosyl-L-methionine (0.4 mg/kcal) administration (102.1 +/- 15.4 nmol/gm after S-adenosyl-L-methionine-ethanol, with 121.4 +/- 11.9 nmol/gm in controls). Ethanol also induced a depletion of glutathione (2.63 +/- 0.13 mumol/gm after ethanol vs. 4.87 +/- 0.36 mumol/gm in controls) that was attenuated by S-adenosyl-L-methionine (3.89 +/- 0.51 mumol/gm in S-adenosyl-L-methionine-methanol vs. 5.22 +/- 0.53 mumol/gm in S-adenosyl-L-methionine controls). There was a significant correlation between hepatic S-adenosyl-L-methionine and glutathione level (r = 0.497; p less than 0.01). After the baboons received ethanol, we observed the expected increase in circulating levels of the mitochondrial enzyme glutamic dehydrogenase: 95.1 +/- 21.4 IU/L vs. 13.4 +/- 1.8 IU/L; p less than 0.001, whereas in a corresponding group of animals given S-adenosyl-L-methionine with ethanol, the values were only 30.3 +/- 7.1 IU/L (vs. 9.6 +/- 0.7 IU/L in the S-adenosyl-L-methionine controls). This attenuation by S-adenosyl-L-methionine of the ethanol-induced increase in plasma glutamic dehydrogenase (p less than 0.005) was associated with a decrease in the number of giant mitochondria (assessed in percutaneous liver biopsy specimens), with a corresponding change in the activity of succinate dehydrogenase, a mitochondrial marker enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ethanol elimination in males and females: relationship to menstrual cycle and body composition

Ethanol pharmacokinetics were determined following oral ethanol, 0.5 gm per kg, in nine normal women and 10 normal men, and related to total body water measured by 3H-water dilution and body fat determined anthropometrically. Ethanol pharmacokinetics were similar in the females throughout the menstrual cycle. No variation was seen in mean peak blood ethanol concentration or elimination rate in the midfollicular (Days 8 to 10) and midluteal (Days 22 to 24) phases. Mean peak blood ethanol values were significantly higher in females (88 +/- 3 mg per 100 ml) than in males (75 +/- 4 mg per 100 ml) (p less than 0.05), and the mean area under the ethanol concentration-time curve was significantly greater in females (241 +/- 12 mg X hr per 100 ml) than in males (177 +/- 11 mg X hr per 100 ml) (p less than 0.001). There was no significant sex difference in mean ethanol elimination rates. The mean apparent volume of distribution of ethanol in female (0.59 +/- 0.02 liter per kg) was less than in males (0.73 +/- 0.02 liter per kg) (p less than 0.001). Both apparent volume of distribution of ethanol and area under curve were significantly correlated with total body water suggesting that the sex differences in ethanol pharmacokinetics were due to sex differences in body water content. The sex differences in ethanol pharmacokinetics may partly explain reports of male-female differences in the natural history of certain ethanol-related disorders.     

Choline fails to prevent liver fibrosis in ethanol-fed baboons but causes toxicity

To determine how choline supplementation affects the liver and whether it can protect against ethanol-induced liver injury, baboons were fed either normal or choline-supplemented diets, each with or without ethanol. Eighteen baboons were pair-fed for 3 to 4 years liquid diets with 50% of total energy as ethanol or isocaloric carbohydrate; ten animals were given our regular diets, whereas in eight the choline content was increased 5-fold. Six additional animals were fed individually with the control diets (with or without additional choline). With both ethanol-containing diets, ethanol intake was comparable and resulted in hepatic steatosis and striking mitochondrial lesions, with increases in serum bilirubin and SGOT, SGPT and glutamate dehydrogenase activities. In addition, of the five animals fed alcohol with the regular diet, one progressed to incomplete cirrhosis and two others developed perivenular and associated perisinusoidal fibrosis. Similarly, in the four baboons fed alcohol with choline supplementation, incomplete cirrhosis developed in one and perivenular fibrosis in two. Collagen deposition was demonstrated by immunoperoxidase with a specific antibody against procollagen Type III. These animals also displayed proliferation of myofibroblasts in the perivenular area and transformation of fat-storing cells to transitional cells in the perisinusoidal space, with associated enhanced collagen fiber deposition. Thus, in baboons, choline supplementation failed to prevent alcohol-induced steatosis and fibrosis. All parameters remained normal in the eight baboons fed the regular control diet. However, in the choline-supplemented controls, serum bilirubin, SGOT and glutamate dehydrogenase activities increased moderately and serum albumin decreased. Occasional fat droplets appeared in hepatocytes with mitochondrial changes (enlargement and alterations of the cristae) and an abundance of "myelin" figures in the cytoplasm, indicating that choline supplementation exerts moderate hepatotoxicity.     

Alcohol Consumption by Young Actively Growing Rats: A Histomorphometric Study of Cancellous Bone

Alcohol consumption by young actively growing rats has been previously demonstrated to decrease bone density. This study addresses the mechanism of alcohol action on the early phases of bone growth and development using histomorphometric techniques. Four-week-old, female Sprague-Dawley rats were divided into three groups. Alcohol-treated animals were fed a modified Lieber-DeCarli diet ad libitum containing 35% ethanol-derived calories, whereas the pair-fed animals (weight-matched to ethanol rats) received an isocaloric liquid diet in which maltose-dextrin-substituted calories were supplied by ethanol. Chow animals were fed a standard rat chow ad libitum. Proximal tibiae, including epiphyseal growth plate, were removed for analysis after 2,4, 6, or 8 weeks on the diets. Trabecular volume and number were greatly reduced in the alcohol-fed animals; however, bone formation rates and mineralization rates were normal. Epiphyseal growth rate and proliferation rate were essentially stopped in the alcohol-fed animals.     

Metabolic effects of moderate alcohol intake with meals in insulin-dependent diabetics controlled by artificial endocrine pancreas (AEP) and in normal subjects

In order to evaluate the effects of moderate alcohol intake on intermediate metabolites, five normal subjects and five euglycemic insulin-dependent diabetics (IDDM) were administered two different isocaloric diets; in one diet 35% of the caloric intake consisted of red wine. The insulin-dependent diabetics were connected to an artificial endocrine pancreas (AEP), and glucose levels were continuously monitored. Blood lactate, pyruvate, acetoacetate (AcAc), 3-hydroxybutyrate (3-OHB), glycerol, free fatty acids (FFA), and alanine levels were measured over a 15-hour period from 9 AM to 12 PM. The results showed that alcohol intake did not significantly influence the glucose profiles in either group (111 +/- 4 mg/100 ml versus 110 +/- 4 mg/100 ml for IDDM; 72 +/- 2 mg/100 ml versus 82 +/- 3 mg/100 ml for controls, 15-hour mean +/- SEM), but in both groups it induced a marked increased in the levels of lactate (1.115 +/- 0.067 mM/liter with alcohol versus 0.706 +/- 0.031 mM/liter without alcohol for IDDM; 0.847 +/- 0.052 mM/liter with alcohol versus 0.666 +/- 0.035 mM/liter without alcohol for controls), in the lactate/pyruvate ratio (24.04 +/- 2.12 with alcohol versus 11.42 +/- 0.20 without alcohol for IDDM; 20.84 +/- 2.16 with alcohol versus 11.62 +/- 0.27 without alcohol for controls), in the levels of 3-OHB (0.081 +/- 0.007 mM/liter with alcohol versus 0.046 +/- 0.003 mM/liter without alcohol for IDDM; 0.067 +/- 0.007 mM/liter with alcohol versus 0.025 +/- 0.002 mM/liter without alcohol for controls) and in the 3-OHB/AcAc ratio (1.452 +/- 0.153 with alcohol versus 0.599 +/- 0.036 without alcohol for IDDM; 1.723 +/- 0.198 with alcohol versus 0.439 +/- 0.040 without alcohol for controls) because of a more reduced redox state. Alcohol intake during meals depressed alanine concentration, while glycerol levels showed a transient increase. Reduced blood FFA concentrations after alcohol intake were observed only in controls. This study demonstrates that moderate alcohol intake with meals also affects intermediate metabolites despite euglycemia. These effects were similar both in normal subjects and in IDDM, even if the harmful effects of alcohol may be enhanced by poor metabolic control in the latter.     

Osteopenia due to chronic alcohol consumption by young actively growing rats is not completely reversible

Our project was conducted to determine if the deleterious effects of chronic alcohol consumption on growing bone are reversible if the adolescent stops drinking. Four-week old, female, Sprague-Dawley rats were housed and maintained in an AAALAC-accredited facility. Six animals each were placed on alcohol-fed (35% ethanol-derived calories), pair-fed or chow-fed diets for 2 or 4 weeks. A recovery group of six animals was alcohol-fed for 2 weeks followed by an additional 2 weeks of chow feeding. This group was pair-fed to an additional group of six animals that received liquid diet, pair fed to the recovery group for 2 weeks followed by 2 weeks on a pair-fed chow diet. Blood alcohol concentrations averaged 309 +/- 9 mg/dl. Morphological parameters of the femur, such as length, diameter, and volume were smaller in alcohol treated animals at both 2 and 4 weeks of feeding. Femur length and volume of recovery alcohol-fed animals were more than either 2- or 4-week alcohol-fed animals, but they were not as great as the same-age 4-week pair-fed or chow-fed animals. Diameter was similar to the 4-week alcohol-fed, but less than the chow-fed. Femur density was reduced at all time periods in the alcohol-fed animals. The recovery alcohol-fed animals had greater density than the 2-week alcohol, but not the 4-week alcohol-fed animals. They did not, however, reach 4-week chow- or pair-fed levels. Tibia BV/TV was reduced in the 2- and 4-week alcohol- and pair-fed animals. BV/TV was greater in the recovery animals than either 2- or 4-week alcohols, but not as great as the chow-fed animals. At 2 weeks, calorie deprivation caused a reduction in insulin-like growth factor-1 (IGF-1) that was reduced even more by alcohol. By 4 weeks, the calorie deprivation was no longer seen, but alcohol continued to reduce the values. Two weeks of alcohol followed by 2 weeks of chow diet returned the IGF-1 values to almost normal, but significantly different levels. The apparent improvement was probably due to continued growth of the young bones and not a regaining of bone lost during alcohol consumption.     

Ethanol: A Gonadal Toxin in the Mature Rat of Both Sexes

A diet containing 5% ethanol, accounting for 36% of the total calories or a similar diet in which dextrimaltose was isocalorically substituted for ethanol, was fed to sexually mature adult male and female rats to determine whether alcohol feeding of such animals could produce gonadal failure as it does in weanling animals. After 4 mo of such feeding, alcohol-fed animals of both sexes, when compared to isocalorically fed controls, demonstrated gonadal atrophy. Such atrophy was manifested by loss of ovarian (p < 0.05) and testicular (p < 0.01) mass, reduced sex steroid levels [progesterone in females and testosterone in males (both p < 0.05)], and atrophy of sex steroid responsive tissues. Such atrophy in the female rats studied was manifested by macroscopic and histologic evidence of loss of estrogen effect, while in the male only histologic evidence for loss of androgen stimulation could be demonstrated. In both male and female animals fed alcohol plasma luteinizing hormone (LH) levels were not increased as would be expected in the presence of such gonadal failure. In contrast, follicle-stimulating hormone (FSH) levels were significantly increased (p < 0.01) in all alcohol-fed animals when compared to isocalorically fed sex-matched controls. These findings confirm and extend our prior studies that demonstrate that alcohol is a gonadal toxin. Moreover, they demonstrate that alcohol feeding to sexually mature animals is associated with a central hypothalamic-pituitary defect in LH but not FSH secretion, as has been shown to exist previously in humans. Thus, alcohol is capable of producing gonadal injury in animals and presumably in man after, as well as before, puberty if ingested in sufficient quantities over a long enough interval.     

Honey-induced stimulation of blood ethanol elimination and its influence on serum triacylglycerol and blood pressure in man

The effect of honey on blood alcohol metabolism and the accompanying changes in serum triacylglycerol and blood pressure were investigated using volunteers. Fifty consenting undergraduates in apparent good health, between the ages of 15 and 30 years (23.6 +/- 7.4), were recruited for the study. The subjects were moderate alcohol drinkers (<30 g ethanol/day), matched in body weight and frame size. The participants were given ethanol (0.5 g/kg) and ethanol + honey (0.5 g/kg + 1.25 ml/kg) on two different occasions separated by 1 week. The results show that honey significantly (p < 0.01) increased blood alcohol disappearance and elimination rates by 32.4 and 28.6%, respectively, but reduced the intoxication time (that is, the time taken to attain zero blood alcohol level) and its degree (the peak blood alcohol level) by 30.0 and 4.4%. Ethanol + honey further increased serum triacylglycerol and blood pressure by 20.8 and 1.3/1.4% when compared with the proportion induced by ethanol after about 10 h of ingestion. The occasional use of honey as an anti-intoxicating agent may be approved. Meanwhile, further studies on how to ameliorate or prevent the associated increase in serum triacylglycerol and blood pressure is required.