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.

Gender comparisons in non-acute cardiac symptom recognition and subsequent help-seeking decisions: a mixed methods study protocol

Introduction: Coronary heart disease (CHD) is one of the leading causes of death in both men and women worldwide. Despite the common misconception that CHD is a ‘man's disease’, it is now well accepted that women endure worse clinical outcomes than men following CHD-related events. A number of studies have explored whether or not gender differences exist in patients presenting with CHD, and specifically whether women delay seeking help for cardiac conditions. UK and overseas studies on help-seeking for emergency cardiac events are contradictory, yet suggest that women often delay help-seeking. In addition, no studies have looked at presumed cardiac symptoms outside an emergency situation. Given the lack of understanding in this area, an explorative qualitative study on the gender differences in help-seeking for a non-emergency cardiac events is needed. Methods and analysis: A purposive sample of 20–30 participants of different ethnic backgrounds and ages attending a rapid access chest pain clinic will be recruited to achieve saturation. Semistructured interviews focusing on help-seeking decision-making for apparent cardiac symptoms will be undertaken. Interview data will be analysed thematically using qualitative software (NVivo) to understand any similarities and differences between the way men and women construct help-seeking. Findings will also be used to inform the preliminary development of a cardiac help-seeking intentions questionnaire. Ethics and dissemination: Ethical approvals were sought and granted. Namely, the University of Westminster (sponsor) and St Georges NHS Trust REC, and the Trust Research and Development Office granted approval to host the study on the Queen Mary's Roehampton site. The study is low risk, with interviews being conducted on hospital premises during working hours. Investigators will disseminate findings via presentations and publications. Participants will receive a written summary of the key findings.