Dose-related effects of red wine and alcohol on hemodynamics, sympathetic nerve activity, and arterial diameter

The cardiovascular benefits of light to moderate red wine consumption often have been attributed to its polyphenol constituents. However, the acute dose-related hemodynamic, vasodilator, and sympathetic neural effects of ethanol and red wine have not been characterized and compared in the same individual. We sought to test the hypotheses that responses to one and two alcoholic drinks differ and that red wine with high polyphenol content elicits a greater effect than ethanol alone. Thirteen volunteers (24-47 yr; 7 men, 6 women) drank wine, ethanol, and water in a randomized, single-blind trial on three occasions 2 wk apart. One drink of wine and ethanol increased blood alcohol to 38 +/- 2 and 39 +/- 2 mg/dl, respectively, and two drinks to 72 +/- 4 and 83 +/- 3 mg/dl, respectively. Wine quadrupled plasma resveratrol (P < 0.001) and increased catechin (P < 0.03). No intervention affected blood pressure. One drink had no heart rate effect, but two drinks of wine increased heart rate by 5.7 +/- 1.6 beats/min; P < 0.001). Cardiac output fell 0.8 +/- 0.3 l/min after one drink of ethanol and wine (both P < 0.02) but increased after two drinks of ethanol (+0.8 +/- 0.3 l/min) and wine (+1.2 +/- 0.3 l/min) (P < 0.01). One alcoholic drink did not alter muscle sympathetic nerve activity (MSNA), while two drinks increased MSNA by 9-10 bursts/min (P < 0.001). Brachial artery diameter increased after both one and two alcoholic drinks (P < 0.001). No beverage augmented, and the second wine dose attenuated (P = 0.02), flow-mediated vasodilation. One drink of ethanol dilates the brachial artery without activating sympathetic outflow, whereas two drinks increase MSNA, heart rate, and cardiac output. These acute effects, which exhibit a narrow dose response, are not modified by red wine polyphenols.     

Modulation of cytochrome P450 activity in the kidney of rats following long-term red wine exposure

Cytochrome P450 (CYP)-dependent oxidation of lauric acid, p-nitrophenol and ethanol by microsomal fractions of kidney were studied in control rats and in animals given either ethanol, red wine, or alcohol-free red wine for 10 weeks. Ethanol increased the total CYP content and specifically CYP 2E1, as well as p-nitrophenol and ethanol oxidation. The effects of ethanol treatment on the content and activity of CYP 2E1 were attenuated when red wine was administered, while the alcohol-free red wine values were similar to those of the control group. Although lauric acid hydroxylation was decreased by red wine treatment, the content of CYP 4A1 was not influenced by drinking fluids. We conclude that red wine administration attenuates the ethanol-induced enhancement of microsomal activities dependent on CYP 2E1 of rat kidney. Our results suggest that the non-alcoholic constituents of red wine could account for this modulation.     

Epidermal growth factor increases tissue antioxidant enzyme activities in ethanol-induced gastric injury in rat

The aim of the present study is to investigate whether the antioxidant mechanisms are involved in epidermal growth factor (EGF)-mediated protection from ethanol-induced gastric damage. Twenty four female Sprague-Dawley rats were assigned into 3 groups; control (C) group (n=8) was given physiologic saline by gavage; ethanol (E) group (n=8) was given 1 ml of 80% ethanol (v/v) in distilled water by gavage and EGF group (n=8) was given EGF (100 mg/kg-body wt.) intraperitonealy half an hour before the administration of ethanol. The protein carbonyl content was significantly higher in the E group than the C group (p<0.01). On the other hand, EGF decreased the protein carbonyl content in the EGF group (p<0.01). Gastric myeloperoxidase activity increased significantly after the administration of ethanol (p<0.01). The administration of EGF decreased significantly the myeloperoxidase activity (p<0.01). Although ethanol caused a slight decrease in the catalase activity, no statistical significance was observed between groups E and C. The catalase activity increased significantly after EGF treatment (p<0.01). The superoxide dismutase activity decreased significantly in the E group when compared to the C group (p<0.05) while it was found to be increased significantly in the EGF group in comparison with the E group (p<0.01). In summary, the present results indicate that the gastroprotective effect of EGF in the experimental lesions induced by ethanol could be attributed to its property such as to augment the antioxidant enzyme activities.     

Male and female reproductive toxicity induced by sub-chronic ethanol exposure in CF-1 mice

Since genetic damage induced by ethanol exposure is controversial and incomplete and because germ and somatic cells constitute bioindicators for monitoring reproductive toxicity and genotoxic actions of ethanol consumption, the purpose of the present investigation was to evaluate morphological sperm, oocyte alterations and parental genotoxic effects after sub-chronic ethanol intake in the CF-1 outbred mouse strain. Ethanol 10% was administered to CF-1 adult male (treated males, TM) and female (treated females, TF) mice for 27 days, whereas water was given to controls from both sexes too (CM and CF). Post-treatment micronucleus frequency (MN-PCE/1,000/mouse) and gamete morphology were evaluated. To test whether change of female reproductive status results in maternal genotoxicity, CF-1 females received ethanol 10% (exposed group, periconceptionally treated females (PTF)) or water (control group, pregnant control females (PCF)) in drinking water for 17 days previous and up to 10 days of gestation. TM had a high percentage of abnormal spermatozoa vs CM (p < 0.001) and elevated parthenogenetic activated oocyte frequency appeared in TF vs CF (p < 0.001). Sub-chronic ethanol ingestion induced increased MN frequency in TM and TF (p < 0.01). In PTF, where blood alcohol concentrations were between 19–28 mg/dl, very significantly increased MN frequency was found vs PCF (p < 0.01), whereas MN values were similar to TF. These results show that sub-chronic alcohol ingestion in CF-1 mice produces sperm head dysmorphogenesis and oocyte nuclear anomalies, suggesting that morphological abnormalities in germ cells are probably related to parental genotoxicity after ethanol consumption.     

Prenatal alcohol exposure shortens life span in rats

In a study of the effects of in utero alcohol exposure on life span in rats, pregnant rats were intubated twice daily with 3.5 gm/kg alcohol on gestational days 11-21 or with an isocaloric sucrose solution. These latter animals were pair-fed and pair-watered to alcohol-treated animals. A third group served as nontreated ad lib-fed controls. At birth, all offspring were removed from their biological mothers, culled to eight per litter, and placed with nontreated surrogate dams. Alcohol-exposed animals died at a significantly younger age than pair-fed and ad lib controls and never attained the same maximum body weights as control animals. For females prenatally exposed to alcohol, life span was shortened by about 20 weeks; in male cohorts, life span was shortened by about 2.5-7 weeks.     

红葡萄酒对大鼠肝脏抗氧化酶和脂质过氧化的影响

选用雄性SD大鼠,分别灌胃红葡萄酒、酒精及水。实验90 d中每隔30 d处死一批动物,测定大鼠肝脏匀浆组织中的超氧化物歧化酶(Superoxide dismutase SOD)、过氧化氢酶(Catalase CAT)、谷胱甘肽过氧化物酶(Glutathione peroxidase GSH-Px)活性和脂质过氧化产物丙二醛(Malondialdehyde MDA)含量变化。观察摄入红葡萄酒后大鼠肝脏抗氧化酶活性变化及对肝脏脂质过氧化的影响。结果表明,红葡萄酒能提高SOD活性,且SOD活性与灌胃时间、剂量有一定关系;长期红葡萄酒和酒精摄入可诱导CAT活性增强,加剧肝脏的脂质过氧化(LPO)作用;红葡萄酒组、酒精组0.63、1.25 g/kg剂量GSH-Px活性均明显升高(P<0.05),酒精组1.88 g/kg剂量有极显著性差异(P<0.01);试验初期,红葡萄酒大剂量显著降低肝脏中MDA的含量。试验中期,红葡萄酒中大剂量显著降低MDA含量。试验末期,红葡萄酒大剂量和酒精中大剂量显著升高肝脏中MDA含量。     

Modulation of rat liver cytochrome P450 activity by prolonged red wine consumption

Cytochrome P450-dependent oxidation of lauric acid, p-nitrophenol and ethanol by liver microsomal fractions were studied in control rats and in animals given either ethanol, red wine, or alcohol-free red wine for 10 weeks. Ethanol increased the total cytochrome P450 and the isoenzyme 2E1 content, as well as the p-nitrophenol hydroxylation and ethanol oxidation. These effects of ethanol treatment were attenuated by red wine administration. Red wine increased the total antioxidant capacity of plasma, whereas the alcohol-free red wine decreased the cytochrome P450 content and decreased the oxidation of lauric acid, p-nitrophenol and ethanol to values lower than control. It is concluded that red wine administration attenuates the ethanol-induced enhancement in liver microsomal parameters dependent on cytochrome P450 2E1 activity, an affect that seems to be accomplished by the non-alcoholic constituents of red wine known to have antioxidant properties.     

Morphometric and morphological features of the ventral prostate in rats submitted to chronic nicotine and alcohol treatment

Clinical studies analyzing simultaneous nicotine-alcohol use by patients showed important alterations in various organic systems such as: respiratory, digestory, and genital. Also, the prostatic morphology and physiology have been analyzed, specially due to large occurrence of prostatic diseases. Then, this work aimed at determining the structure and ultrastructure of the prostatic stroma and epithelium, as well as the stroma epithelium interactions from rats submitted to simultaneous long-term alcohol-nicotine treatment. A total of 40 male rats were divided into four groups: control group (10 animals) received tap water; alcoholic group (10 animals) received diluted 10% Gay Lussac ethanol; nicotine group (10 animals) received a 0.125mg/100g of body weight dose of nicotine injected subcutaneosly on a daily basis; nicotine-alcohol group (10 animals) received simultaneous alcohol and nicotine treatment. After 90 days of treatment, the animals were sacrificed and samples from the ventral lobe of the prostate were collected and processed for transmission electron and light microscopies. The results showed atrophied epithelium; prostatic intra-epithelial neoplasia; dilated cisterns of the granular endoplasmic reticulum, large amounts of collagen fibers besides inflammatory cells, specially in the alcoholic and nicotine-alcohol groups. Therefore, it could be concluded that the association between alcohol and nicotine caused the impairment of the prostatic secretory process. Moreover, this association is related to prostatic pathogenesis, which could lead to late glandular malignancy.     

The effect of moderate alcohol consumption on fat distribution and adipocytokines

Objective: To investigate the effect of moderate alcohol consumption on fat distribution, adipose tissue secreted proteins (adiponectin and resistin), and insulin sensitivity in healthy middle‐aged men with abdominal obesity. Research Methods and Procedures: Thirty‐four healthy men between 35 and 70 years old, with increased waist circumference (≥94 cm), participated in a randomized, controlled cross‐over design trial. They drank 450 mL of red wine (40 grams of alcohol) or 450 mL of de‐alcoholized red wine daily during 4 weeks. At the end of each treatment period, fat distribution, adipose tissue proteins, and insulin sensitivity index (ISI) were measured. Results: Subcutaneous and abdominal fat contents and body weight did not change after 4 weeks of moderate alcohol consumption. Liver fat (quip index) was slightly higher after consumption of red wine (6.8 ± 0.1) as compared with de‐alcoholized red wine (6.5 ± 0.1) but not significantly different (p = 0.09). Plasma adiponectin concentration increased (p < 0.01) to 6.0 ± 0.1 μg/mL after 28 days of moderate alcohol consumption compared with de‐alcoholized red wine (5.5 ± 0.1 μg/mL). Serum resistin concentrations and ISI were not affected by alcohol consumption. Percentage changes in serum resistin correlated significantly with changes in ISI (r = ?0.69, p < 0.01), whereas this correlation was not present between changes in plasma adiponectin and ISI (r = 0.31, p = 0.22). Discussion: Moderate alcohol consumption for 4 weeks is not associated with differences in subcutaneous and abdominal fat contents or body weight. Thus, the 10% increase in adiponectin was not associated with a change in fat distribution or body weight change.     

Effect of multigeneration alcohol feeding on murine immune system

Mice belonging to F8, F12, F14 and F20 generation of a multigeneration study reared on 20% (v/v) ethanol in water as the sole drinking source were investigated for their immune competence using various parameters. The results indicated lack of any significant effect on delayed type hypersensitivity to dinitro fluorobenzene (DNFB) or sheep red blood cells (SRBC) in mice consuming ethanol. Further, alloskin graft and tumor graft response was similar in both ethanol and water fed mice. Humoral response to SRBC was also intact. However, NK cell activity was reduced significantly in ethanol fed mice. Phagocytic index as assessed by the carbon clearance test was also reduced considerably in mice consuming ethanol. The results clearly indicate that ethanol per se has a significant effect on the nonspecific limb of the immune system, in chronically fed mice.     

Response to rearing in laboratory of the xylophagous grape pest,Xylotrechus arvicola (Coleoptera: Cerambycidae)

Xylotrechus arvicola (Olivier) (Coleoptera: Cerambycidae) is an important pest in vineyards (Vitis vinifera) in the main Iberian wine‐producing regions. Larvae were reared with Semi‐Synthetic Iglesias (SSI) diet over 27 months and two generations in the laboratory. Larval mortality was highest during the first (49.49 %) and second (9.38 %) month of rearing, increasing to 50.52 % during the first month if F2 reared larvae were obtained from an F1 adult female obtained in laboratory. The diet had sufficient nutrients to enable the pest to complete its life cycle within nine months, with F1 larval viability ranging from 23.49 % to 27.97 % and F2 larval viability reduced to 2.07 %. However, the diet did not allow for the completion of additional life cycles and generations (F3, F4,…). Larval mortality increased as the months of rearing (66.13 %, 69.51 % and 89.50 %) and generations (59.10 % and 76.93 % in F1 and F2, respectively) progressed in the laboratory. The larva–adult period of females obtained in the laboratory was longer than for males. In the laboratory, the life cycle was shortened in relation to the life cycle in the field because larvae did not require a cold period to break diapause and start pupation. This indicates that X. arvicola has the potential to complete its life cycle inside grape wood in vineyards of wine‐producing regions with warmer winters.     

Clinical evaluation of a new prostaglandin analog in pigs: 2. Prophylaxis and therapy of anestrus after weaning in sows and first litter gilts

Alfaprostol, a new prostaglandin F(2alpha) (PGF) analog was given in a first trial at two dose levels known to be luteolytic (1 and 2 mg) to 200 sows and first litter gilts at the day of weaning after a 21-day lactation period; 189 controls received saline only. The treatment with alfaprostol shortened the interval to heat (6.0 vs 11.3 days; p<0.01) and increased the percentage of animals coming into heat within 10 days (84.0 vs 65.5%; p<0.01). Fertility to a.i. and litter size at the subsequent parturition were normal. In a second trial, 100 first litter gilts and 100 sows received alfaprostol, 1 or 2 mg, respectively, during July and August when high environmental temperatures tend to increase the rate of anestrus. Again, treatment with alfaprostol shortened effectively the interval to heat (5.9 vs 17.4 days in gilts, p<0.001; 5.6 vs 9.7 days in sows; p<0.01) and greatly increased the number of animals in heat (81 vs 47% in gilts, 83 vs 62% in sows; p<0.001). The effect on the seasonal incidence of clinical anestrus was marked; it was more pronounced in gilts than in sows, expressed by the length of time it took to resume cyclic functions and the lower percentage of animals coming into heat (p<0.001). The effect of alfaprostol was equally well expressed in first litter gilts and sows. In a third trial, 295 anestrous sows and gilts were treated on day 22 after weaning with either 2 mg alfaprostol, or 400 I.U. PMSG+200 I.U. hCG, or saline. Within five days after weaning, 38% of the alfaprostol treated, and 78% and 23% of the animals treated with PMSG/hCG and saline came into heat.     

Modulation of NK cell activity by moderate intensity endurance training and chronic ethanol consumption.

Chronic ethanol consumption can suppress natural killer (NK) cell activity. Exercise after ethanol administration may enhance blood ethanol clearance, which may benefit the immune response. This study examined the effects of moderate intensity endurance training and chronic ethanol consumption (20% wt/vol) on splenic NK cell activity. Mice were assigned to one of four groups: sedentary, water drinking (SED-H2O); sedentary, ethanol consuming (SED-EtOH); trained, water drinking (TR-H2O), and trained, ethanol consuming (TR-EtOH). TR groups ran 60 min/day, 5 days/wk, at 12 m/min for 10 wk. Mice were killed 48 h after exercise. Baseline NK cell activity was suppressed 30% in TR and EtOH groups compared with SED-H2O controls. Activation with recombinant human interleukin-2 increased cytolytic activity in all groups four- to fivefold. These results indicate that training did not abrogate the effects of chronic ethanol consumption on NK cell activity. Furthermore, moderate endurance training may contribute to suppressed nylon wool-enriched NK cell activity in murine splenocytes for as long as 48 h after exercise.     

Method of ethanol administration as a confounding factor in studies of fetal alcohol syndrome

Female Sprague-Dawley rats were fed a complete liquid diet containing either 5.5% ethanol (mean daily intake of about 9g of ethanol per kg body weight) or an isocaloric amount of dextrose (control group), with additional water available $\text{ad}$$\text{libitum}$. The diets were fed for four weeks prior to and throughout pregnancy. On day 20 of gestation cardiac output and blood flow to the placeta, heart, kidneys and uterus were measured and plasma osmolality and muscle dry weight were determined. No significant differences were seen between alcohol and control groups with respect to litter size, fetal weight, maternal cardiac output, blood flow to the placenta or other organs, plasma osmolality, or muscle dry weight. This contrasts with previous experiments in which a similar quantity of alcohol (as % calories) was offered in drinking water (equivalent to a mean daily ethanol intake of 10g/kg body weight). Under those conditions fetal weight was reduced, blood flow to the plascenta was reduced, and plasma osmolality and muscle dry weight were increased, indicating a moderate degree of dehydration. It is concluded that the effect of ethanol ingestion is influenced by the mode of administration of the ethanol. Dehydration may be a confounding factor in studies of animal models of fetal alcohol syndrome, although it is not possible to rule out a differential metabolic response to alcohol, depending on the mode of administration.     

Differential effects of ethanol ingestion on somatostatin content, somatostatin receptors and adenylyl cyclase activity in the frontoparietal cortex of virgin and parturient rats

Chronic ethanol ingestion decreases the number of somatostatin (SRIF) receptors in the rat frontoparietal cortex and female sex hormones modulate the effects of ethanol in the brain. Therefore, we investigated the differential effects of ethanol consumption on the SRIFergic system in the frontoparietal cortex of virgin and parturient rats given ethanol in their drinking water before and during gestation. In parturient rats, ethanol consumption decreased the density of SRIF receptors (25%, p<0.01 vs control parturient group) whereas the SRIF-like immunoreactivity (SRIF-LI) content was increased (140%, p<0.01). In virgin rats, ethanol ingestion decreased the density of SRIF receptors (42%, p<0.01) more than in alcoholic parturient rats. SRIF-LI levels were unaffected. The inhibitory effect of SRIF on basal and forskolin-stimulated adenylyl cyclase was significantly lower in alcoholic virgin rats as compared to alcoholic parturient rats. No differences in the levels of the G inhibitory (Gi) alpha1 and Gialpha2 proteins were observed among the experimental groups. These results suggest that gestation may confer partial resistance to the ethanol-induced effect on the SRIFergic system.     

Effects of delta sleep-inducing peptide on electrophysiological parameters of sleep during alcohol withdrawal in rats

In rats with the persistent alcohol motivation the electrophysiological sleep pattern was studied during ethanol intake, after 24 and 48 hours of alcohol withdrawal. It was established that during the voluntary ethanol intake rats may be divided into two groups: with comparative deficit (1st group) and comparative abundance (2nd group) of REM sleep. Alcohol withdrawal caused differential alterations of sleep-wakefulness cycle: in the 1st group of rats REM sleep was more suppressed while in the 2nd group--more increased in comparison to those during ethanol intake. In all animals the SWS depression, increase of awakenings, the aggravation of falling asleep and decrease of sleep depth were observed. DSIP (0.1 mg/kg, i.p. 1 hour before sleep recording) was found to regulate sleep disorders caused by ethanol withdrawal. It makes the neuropeptide possible to be recommended for ethanol withdrawal syndrome treatment in clinical practice.     

酒精对丙酸睾酮诱导的小鼠前列腺增生的作用

目的：探讨酒精对丙酸睾酮引起的小鼠前列腺增生（BPH）的作用及其生殖毒性。方法：成年雄性昆明系小鼠70只随机分为空白对照组（Control）、阴性对照组（Negative control,sc大豆油25 mg/（kg·d）,ig蒸馏水7.5 ml/（kg·d）,连续处理7 d、21 d）、酒精7 d和21 d组（AL7和AL21,ig 50°白酒7.5 ml/（kg·d）,连续处理7 d、21 d）,丙酸睾酮7 d和21 d组（TP7和TP21,sc丙酸睾酮注射液25 mg/（kg·d）,连续处理7 d、21 d）,丙酸睾酮+酒精7 d组（TP+AL7,sc丙酸睾酮注射液25 mg/（kg·d）,ig50°白酒7.5 ml/（kg·d）,连续处理7 d）,每组10只。末次处理24 h后处死小鼠,计算小鼠前列腺和睾丸系数,检测精子参数,测定睾丸和前列腺组织中自由基水平、抗氧化能力,观察前列腺组织病理学变化。结果：与对照组、TP7 d组、AL7和AL21 d组相比,TP+AL7 d组的前列腺系数显著提高、精子数量和质量显著降低、前列腺和睾丸MDA含量显著升高、SOD和GPx酶活力显著下降（P均< 0.05）;与TP21 d组相比,TP+AL7 d组的前列腺系数无显著差别（P>0.05））。结论：丙酸睾酮和酒精共同处理7 d就可以达到典型的前列腺增生（BPH）状态,并引起睾丸及精子的损伤,导致生殖系统的氧化应激反应增强,说明酒精对丙酸睾酮引起的小鼠前列腺增生有明显的促进作用。     

Symmetrical effect of pre-exposure between alcohol and morphine on conditioned taste aversion

It has previously been reported that pre-exposure to a psychoactive drug can block the conditioned taste aversion associated with that drug. This study was an attempt to investigate alcohol-morphine interactions using this pre-exposure paradigm. After two weeks of adaptation to a schedule of daily 30-minute access to water, rats were pre-exposed to morphine, ethanol, or the respective vehicle control every second day for three days before (Days 1, 3, 5) and after the first conditioning day (Days 8, 10, 12). On conditioning days (Days 7, 14), animals were first presented with a saccharin solution for 30 minutes following which animals that were pre-exposed to morphine were injected with ethanol while those pre-exposed to ethanol were administered with morphine. Saccharin was again presented on three more occasions (Days 21, 28, 35) without drug injection. Using the percent change in saccharin consumed from the first presentation as a measure of aversion, it was found that pre-exposure to morphine blocked ethanol conditioned taste aversion. Similarly, animals pre-exposed to ethanol showed less aversion to the saccharin paired with morphine. This is the first demonstration of a symmetrical relationship between alcohol and the opiates.     

IGFR-I expression and structural analysis of the hard palatine mucosa in an ethanol-drinking rat strain (UChA and UChB)

The study analyzed the effects of chronic alcohol ingestion on the ultrastructure of the lining epithelium of the hard palatine mucosa of rats UChA and UChB (lines with voluntary alcohol consumption) in order to contribute to the understanding of the consequences of alcohol abuse for the morphology of the digestive system. Thirty female adult animals aged 120 days were divided into three experimental groups. (1) Ten UChA rats (genetically low ethanol consumer) with voluntary intake of 10% v/v (5.45 g/kg/day) ethanol solution and water. (2) Ten UChB (genetically high ethanol consumer) rats with voluntary intake of 10% v/v (7.16 g/kg/day) ethanol solution and water. (3) Ten Wistar rats with voluntary ad libitum water intake (control group). Both groups received Nuvital pellets ad libitum. The IGFR-I expression was intense in both experimental groups. The epithelial cells of the alcoholic rats UChA and UChB showed many alterations such as the presence of lipid droplets, altered nuclei, nuclei in corneum layer and disrupted mitochondria. It was concluded that ethanol intake induces ultrastructural lesions in the hard palatine mucosa.