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.

A strategy-based framework for assessing the flood resilience of cities – the Hamburg case study

Climate change and continuous urbanization contribute to an increased urban vulnerability towards flooding. Only relying on traditional flood control measures is recognized as inadequate, since the damage can be catastrophic if flood controls fail. The idea of a flood-resilient city – one which can withstand or adapt to a flood event without being harmed in its functionality – seems promising. But what does resilience actually mean when it is applied to urban environments exposed to flood risk, and how can resilience be achieved? This paper presents a heuristic framework for assessing the flood resilience of cities, for scientists and policy-makers alike. It enriches the current literature on flood resilience by clarifying the meaning of its three key characteristics – robustness, adaptability and transformability – and identifying important components to implement resilience strategies. The resilience discussion moves a step forward, from predominantly defining resilience to generating insight into “doing” resilience in practice. The framework is illustrated with two case studies from Hamburg, showing that resilience, and particularly the underlying notions of adaptability and transformability, first and foremost require further capacity-building among public as well as private stakeholders. The case studies suggest that flood resilience is currently not enough motivation to move from traditional to more resilient flood protection schemes in practice; rather, it needs to be integrated into a bigger urban agenda.