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.

Crowdsourcing User-Contributed Solutions to Aerospace Product Development Issues through Micro-Blogging

Revenue and production output of the United Kingdom’s Aerospace Industry (AI) is growing year on year and the need to develop new products and innovative enhancements to existing ranges is creating a critical need for the increased utilisation and sharing of employee knowledge. The capture of employee knowledge within the UK’s AI is vital if it is to retain its pre-eminent position in the global marketplace. Crowdsourcing, as a collaborative problem solving activity, allows employees to capture explicit knowledge from colleagues and teams and also offers the potential to extract previously unknown tacit knowledge in a less formal virtual environment. By using micro-blogging as a mechanism, a conceptual framework is proposed to illustrate how companies operating in the AI may improve the capture of employee knowledge to address production-related problems through the use of crowdsourcing. Subsequently, the framework has been set against the background of the product development process proposed by Maylor in 1996 and illustrates how micro-blogging may be used to crowdsource ideas and solutions during product development. Initial validation of the proposed framework is reported, using a focus group of 10 key actors from the collaborating organisation, identifying the perceived advantages, disadvantages and concerns of the framework; results indicate that the activity of micro-blogging for crowdsourcing knowledge relating to product development issues would be most beneficial during product conceptualisation due to the requirement for successful innovation.