Linda La Grange

Protective effects of the flavonoid mixture, silymarin, on fetal rat brain and liver

We investigated the possibility that the flavonoid mixture, silymarin (SY), administered as the compound Silymarin Phytosome (PHYTO), could protect the fetus from maternally ingested EtOH. Seventy-six female rats were randomly assigned to one of seven groups: pair-fed control; chow fed control; EtOH; and four groups receiving EtOH and PHYTO in varying dosages. All groups except the chow-fed control were maintained on a liquid diet. On day 1 of pregnancy the dams began the treatment protocol. On day 21 of pregnancy the rats were sacrificed and the fetuses removed. Gamma glutamyl transpeptidase (GGTP) activity was determined for liver and brain tissue from both the fetuses and the dams. GGTP activity in the EtOH/silymarin treatment groups did not differ significantly from that observed for the pair-fed control group. The observed GGTP activity levels for the EtOH-only group were significantly higher than those attained by the pair-fed control group. Although GGTP activity did not vary significantly with the quantity of PHYTO administered, as PHYTO dose was increased, GGTP activity decreased.

Alcohol consumption: biochemical and personality correlates in a college student population

The frequency of alcohol use among a subject population of 28 male and 60 female college students was assessed using the Student Alcohol and Drug Use Survey (STADUS). Data were also collected on personality traits as measured by the Sensation Seeking Scale V (SSSV) and the Eysenck Personality Questionnaire (EPQ). Finally, three biochemical variables were assessed: monoamine oxidase (MAO) activity, dopamine beta hydroxylase (DBH) activity, and testosterone levels. Among males, high SSSV scores, high testosterone levels, and low MAO activity contributed to the variance in alcohol use, whereas among females, a significant proportion of the variability in alcohol use was accounted for by high SSSV scores, high DBH activity, and younger age.

The effects of ethanol and silymarin treatment during gestation on spatial working memory.

BackgroundUsing a rat model we have found that the bioflavonoid silymarin (SY) ameliorates some of the negative consequences of in utero exposure to ethanol (EtOH). In the current study our aim was to determine if spatial working memory (SWM) was impaired in offspring whose mothers were maintained on a liquid diet containing EtOH during different gestational weeks. We also determined if SWM was altered with a concomitant administration of SY with EtOH during specific gestational weeks.MethodsWe provided pregnant Fischer/344 rats with liquid diets containing 35% EtOH derived calories (EDC) during specific weeks of the gestational period. A silymarin/phospholipid compound containing 29.8% silybin co-administered with EtOH was also administered during specific weeks of the gestational period. We tested SWM of the offspring with a radial arm maze on postnatal day (PND) 60. After testing the rats were sacrificed and their brains perfused for later analysis.ResultsWe observed SWM deficits, as well as a significantly lower brain weight in female offspring born of mothers treated with EtOH during the third week of gestation in comparison to mothers treated during either the first or second weeks of gestation. Rats from any group receiving EtOH in co-administration with SY showed no significant deficits in SWM.ConclusionEtOH treatment during the last week of gestation had the greatest impact on SWM. The addition of SY to the EtOH liquid diet appeared to ameliorate the EtOH-induced learning deficits.

The Use of a Silymarin/Phospholipid Compound as a Fetoprotectant from Ethanol-Induced Behavioral Deficits

We have replicated an earlier study in which silymarin/ phytosome appeared to prevent deficits in social memory function in male rats exposed in utero to ethanol (EtOH).1 Female rats were included in the current study as well as a second behavioral test, the radial arm maze. Pregnant Sprague-Dawley rats were provided with liquid diets containing 35% ethanol derived calories (EDC). The silybin/phospholipid compound (SI) was co-administered with EtOH to the experimental group. The offspring were tested at age 90 days on the social recognition task and at 75 days on the radial arm maze. Female EtOH-exposed offspring performed more poorly on the radial arm maze than did female EtOH/SI offspring and the offspring of female controls. Male EtOH-exposed offspring were less able to form social memories than the male EtOH/SI offspring and the offspring of male controls.

Impact of in utero exposure to EtOH on corpus callosum development and paw preference in rats: protective effects of silymarin

BackgroundUsing a rat model we have found that the bioflavonoid silymarin (SY) ameliorates some of the negative consequences of in utero exposure to ethanol (EtOH). In the current study our aim was to determine if laterality preference and corpus callosum development were altered in rat offspring whose mothers were provided with a concomitant administration of SY with EtOH throughout gestation.MethodsWe provided pregnant Fisher/344 rats with liquid diets containing 35% ethanol derived calories (EDC) throughout the gestational period. A silymarin/phospholipid compound containing 29.8% silybin was co administered with EtOH to a separate experimental group. We tested the offspring for laterality preference at age 12 weeks. After testing the rats were sacrificed and their brains perfused for later corpus callosum extraction.ResultsWe observed incomplete development of the splenium in the EtOH-only offspring. Callosal development was complete in all other treatment groups. Rats from the EtOH-only group displayed a left paw preference; whereas control rats were evenly divided between right and left paw preference. Inexplicably both SY groups were largely right paw preferring.ConclusionsThe addition of SY to the EtOH liquid diet did confer some ameliorative effects upon the developing fetal rat brain.

Fetoprotectivity of the flavanolignan compound siliphos against ethanol‐induced toxicity

Of the three flavanolignans that are found in silymarin (Silybum marianum [L.] Gaertn.), silybin is thought to be the primary therapeutic constituent. To test the capacity of silybin to protect the rat fetus from toxic effects of maternally ingested EtOH we did the following: Adult female rats were assigned to one of four groups; EtOH, EtOH/silybin, pair‐fed control, and chow fed control. Silybin was orally administered as Siliphos®, which is one part silybin to two parts phosphatidylcholine. All groups except the chow‐fed control were maintained on a liquid diet throughout pregnancy. On day 21 of pregnancy the rats were killed and the fetuses removed. Gamma glutamyl transpeptidase (GGTP) activity and glutathione (GSH) levels were determined for liver and brain tissue for both the fetuses and the dams. Maternal and fetal GGTP activity in the EtOH rats was significantly higher than that of pair‐fed controls, whereas the GGTP activity observed in the Siliphos®/EtOH rats was not elevated. Fetal mortality rates in the EtOH rats significantly exceeded those of all three other groups. Copyright

Adjudicated adolescent males: measures of urinary 5-hydroxyindoleacetic acid and reactive hypoglycemia

Abstract A psychological model identified as the ‘low serotonin syndrome’ has been posited to explain the associated between certain biological characteristics such as low levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) and reactive hypoglycemia; and aggressive, violent, or impulsive behavior. Thirty-seven male adolescents adjudicated for violent offenses were compared with 37 middle school adolescents on the following measures: urinary 5-HIAA levels, response to the glucose tolerance test (GTT), and scores on the Impulsive Sensation Seeking (ImpSS) and Aggression-Hostility (AGG-Host) subscales of the Zuckerman-Kuhlman Personality Questionnaire (ZKPQ). The mean urinary 5-HIAA value in the adjudicated subjects was significantly lower than the 5-HIAA mean for the middle school controls. In response to the GTT, the mean blood glucose nadir recorded for the adjudicated group was also significantly lower than the glucose nadir mean obtained from the control subjects. Scores on the ImpSS subscale did not differ significantly whereas the adjudicated adolescents scored significantly higher on the Agg-Host subscale than did the control subjects.

Monoamine oxidase levels in females: Relationships to sensation seeking, alcohol misuse, physical fitness, and menstrual cycle

Abstract Levels of the enzyme monamine oxidase (MAO) have been found to correlate negatively with a number of personality traits as well as certain psychiatric disorders. These negative correlations are stronger and more consistently observed among males. Using female participants, the current study was undertaken to determine the extent of any relationships that might exist between levels of MAO, drug/alcohol use, and those personality traits measured by the Sensation Seeking Scale V and the Eysenck Personality Questionnaire. Data regarding physical fitness and date of menstrual cycle onset were also collected. Although not statistically significant, MAO levels were correlated with a number of the personality measures in the predicted direction. There was also a fairly strong negative correlation between alcohol consumption and MAO levels and a significantly positive correlation between physical fitness and MAO levels.

Personality Correlates of Alcohol Consumption and Aggression in a Hispanic College Population.

The authors examined the association between alcohol consumption and aggression from a personality trait perspective with 92 self-identified Hispanic college students. They partially replicated a study by Quigley, Corbett, and Tedeshi, which examined the relationships between desired image of power, alcohol expectancies, and alcohol-related aggression. Among male participants, impulsivity did not correlate with either alcohol consumption or frequency of fighting, whereas with females there was a strong positive correlation between impulsivity and alcohol consumption and a weak positive correlation between impulsivity and frequency of fighting. When the results were compared to those of Quigley et al., it was found that the Hispanic participants drank and fought less. The best predictor variable for male alcohol consumption was the desire to be viewed as “tough.” “Activity” was the primary predictor for female alcohol consumption.

The Effects of Salty and Nonsalty Food on Peak Breath Alcohol Concentration and Divided Attention Task Performance in Women

There is recent evidence that gender-based patterns of alcohol consumption are becoming less dissimilar and that, per capita, women are consuming more alcohol than ever before. Therefore, a better understanding of the acute effects of moderate alcohol consumption in women is essential to establishing reliable health and safety educational information. To address one component of health and safety information, we sought to determine if peak breath alcohol concentrations (BAC) could be manipulated by varying the amount of sodium our women participants ingested in a test meal. We also measured the association between BAC and the participants performance on a divided attention (DA) task. The 12 participants were trained to use a computer-generated DA task and subsequently participated in all of four experimental conditions. During each experimental session the participant consumed a placebo drink or a drink containing 0.6 g/kg ethanol and a 220-kcal portion of salted or unsalted pretzels. She then performed four 15-min trials of the DA task, after which the BAC was measured and recorded. Reaction times and mean tracking error were recorded for each DA trial. Experimental sessions took place at the same time on days 7, 8, 9, and 10 of the participants menstrual cycle. The BAC was significantly higher in the ethanol plus sodium condition than in the ethanol with no sodium condition. Reaction times and tracking tasks were impaired in all ethanol conditions. Scores on the DA tasks obtained from the high-sodium group did not differ significantly from those of the low-sodium group. When health care personnel provide drug education for women clients, the possible BAC-elevating effects of consuming high-sodium foods while drinking alcoholic beverages should be discussed.