The effect of acute alcohol exposure on hepatic oxidative stress and function: prevention by micronutrients

Alcohol binge drinking, especially in teenagers and young adults is a major public health issue in the UK, with the number of alcohol related liver disorders steadily increasing. Understanding the mechanisms behind liver disease arising from binge-drinking and finding ways to prevent such damage are currently important areas of research. In the present investigation the effect of acute ethanol administration on hepatic oxidative damage and apoptosis was examined using both an in vivo and in vitro approach; the effect of micronutrient supplementation prior and during ethanol exposure was also studied. The following studies were performed: (1) ethanol administration (75 mmol/kg body weight) and cyanamide pre-treatment followed by ethanol to study elevated acetaldehyde levels with liver tissue analysed 2.5, 6 and 24 hours post-alcohol; (2). Using juvenile animals, 2% betaine supplementation followed by acute ethanol with tissue analysed 24 hrs post ethanol; and (3). Micronutrient supplementation during concomitant ethanol exposure to hepG2 cells. It was found that a single dose of alcohol caused oxidative damage to the liver of rats at 2.5 hr post-alcohol as evidenced by decreased glutathione levels and increased malondialdehyde levels in both the cytosol and mitochondria. Liver function was also depressed but there were no findings of apoptosis as cytochrome c levels and caspase 3 activity was unchanged. At 6 hours, the effect of ethanol was reduced suggesting some degree of recovery, however, by 24 hours, increased mitochondrial oxidative stress was apparent. The effect of elevated acetaldehyde on hepatic damage was particularly evident at 24 hours, with some oxidative changes at earlier time points. At 24 hours, acetaldehyde caused a profound drop in glutathione levels in the cytosol and hepatic function was still deteriorating. Studies examining ethanol exposure to juvenile livers showed that glutathione levels were increased, suggesting an overtly protective response not seen in with older animals. It also showed that despite cytochrome c release into the cytosol, caspase-3 levels were not increased. This suggests that ATP depletion is preventing apoptosis initiation. Betaine supplementation prevented almost all of the alcohol-mediated changes, suggesting that the main mechanism behind alcohol-mediated liver damage is oxidative stress. Results using the hepG2 cell line model showed that micronutrients involved in glutathione synthesis can protect against hepatocyte damage caused by alcohol metabolism, with reduced reactive oxygen species and increased/maintained glutathione levels. In summary, these results demonstrate that both acute alcohol and acetaldehyde can have damaging effects to the liver, but that dietary intervention may be able to protect against ethanol induced oxidative stress.

The effect of smoking nicotine tobacco versus smoking deprivation on motion sickness

BACKGROUND: The experienced smoker maintains adequate nicotine levels by 'puff-by-puff self-control' which also avoids symptomatic nauseating effects of nicotine overdose. It is postulated that there is a varying 'dynamic threshold for nausea' into which motion sickness susceptibility provides an objective toxin-free probe. Hypotheses were that: (i) nicotine promotes motion sickness whereas deprivation protects; and (ii) pleasurable effects of nicotine protect against motion sickness whereas adverse effects of withdrawal have the opposite effect. METHODS: Twenty-six healthy habitual cigarette smokers (mean±SD) 15.3±7.6cigs/day, were exposed to a provocative cross-coupled (coriolis) motion on a turntable, with sequences of 8 head movements every 30s. This continued to the point of moderate nausea. Subjects were tested after either ad-lib normal smoking (SMOKE) or after overnight deprivation (DEPRIV), according to a repeated measures design counter-balanced for order with 1-week interval between tests. RESULTS: Deprivation from recent smoking was confirmed by objective measures: exhaled carbon monoxide CO was lower (P<0.001) for DEPRIV (8.5±5.6ppm) versus SMOKE (16.0±6.3ppm); resting heart rate was lower (P<0.001) for DEPRIV (67.9±8.4bpm) versus SMOKE (74.3±9.5bpm). Mean±SD sequences of head movements tolerated to achieve moderate nausea were more (P=0.014) for DEPRIV (21.3±9.9) versus SMOKE (18.3±8.5). DISCUSSION: Tolerance to motion sickness was aided by short-term smoking deprivation, supporting Hypothesis (i) but not Hypothesis (ii). The effect was was approximately equivalent to half of the effect of an anti-motion sickness drug. Temporary nicotine withdrawal peri-operatively may explain why smokers have reduced risk for postoperative nausea and vomiting (PONV).

Calcium, vitamin D, casein and whey protein intakes and periodontitis among Danish adults

Objective: To investigate whether intakes of Ca, vitamin D, casein and whey are associated with periodontitis and to investigate the possibility of interactions between them. Design: Cross-sectional study. An Internet-based, 267-item FFQ was used to assess dietary intake. Intakes of casein (32·0 g/d), whey proteins (9·6 g/d) and vitamin D (5·8 μg/d) were classified as within v. above the 50th percentile. Ca intake was classified as within v. below age-specific recommendations. Severe periodontitis was defined as having ≥2 inter-proximal sites with clinical attachment loss ≥6 mm (not on the same tooth) and ≥1 inter-proximal site with pocket depth ≥5 mm. Since vitamin D influences Ca absorption, models were stratified by lower and higher (<5·8 v. ≥5·8 µg/d) vitamin D intake. Setting Danish Health Examination Survey (DANHES) 2007–2008. Subjects Adult participants (n 3287) in the oral health study of DANHES 2007–2008. Results Intakes of Ca within recommendations (OR=0·76; 95 % CI 0·58, 0·99), whey ≥9·6 g/d (OR=0·75; 95 % CI 0·58, 0·97) and casein ≥32 g/d (OR=0·75 95 % CI 0·58, 0·97) were associated with lower likelihood of severe periodontitis after adjustment for age, gender, education, smoking, sucrose intake, alcohol consumption, number of teeth, daily brushing, regular visits to the dentist and chronic illness, irrespective of vitamin D intake levels. Intake of vitamin D alone was not associated severe with periodontitis. Conclusions Intakes of Ca, casein and whey protein were inversely associated with periodontitis. Consumption of foods rich in Ca, casein and whey (e.g. dairy foods) should be promoted, as they may contribute to the prevention of periodontitis. Further longitudinal studies are required to confirm these associations.

Calcium, vitamin D, casein and whey protein intakes and periodontitis among Danish adults

OBJECTIVE: To investigate whether intakes of Ca, vitamin D, casein and whey are associated with periodontitis and to investigate the possibility of interactions between them. DESIGN: Cross-sectional study. An Internet-based, 267-item FFQ was used to assess dietary intake. Intakes of casein (32.0 g/d), whey proteins (9.6 g/d) and vitamin D (5.8 mug/d) were classified as within v. above the 50th percentile. Ca intake was classified as within v. below age-specific recommendations. Severe periodontitis was defined as having >/=2 inter-proximal sites with clinical attachment loss >/=6 mm (not on the same tooth) and >/=1 inter-proximal site with pocket depth >/=5 mm. Since vitamin D influences Ca absorption, models were stratified by lower and higher (<5.8 v. >/=5.8 microg/d) vitamin D intake. SETTING: Danish Health Examination Survey (DANHES) 2007-2008. SUBJECTS: Adult participants (n 3287) in the oral health study of DANHES 2007-2008. RESULTS: Intakes of Ca within recommendations (OR=0.76; 95 % CI 0.58, 0.99), whey >/=9.6 g/d (OR=0.75; 95 % CI 0.58, 0.97) and casein >/=32 g/d (OR=0.75 95 % CI 0.58, 0.97) were associated with lower likelihood of severe periodontitis after adjustment for age, gender, education, smoking, sucrose intake, alcohol consumption, number of teeth, daily brushing, regular visits to the dentist and chronic illness, irrespective of vitamin D intake levels. Intake of vitamin D alone was not associated severe with periodontitis. CONCLUSIONS: Intakes of Ca, casein and whey protein were inversely associated with periodontitis. Consumption of foods rich in Ca, casein and whey (e.g. dairy foods) should be promoted, as they may contribute to the prevention of periodontitis. Further longitudinal studies are required to confirm these associations.