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Fructose: Bad sugar's good deeds

Functional Glycomics (09 July 2009) | doi:10.1038/fg.2009.26

Metabolites of fructose protect against oxidative damage in astroglial cells exposed to hydrogen peroxide.

'Relative oxidative status' of astroglial cells exposed to H2O2 in glucose- (left) or fructose-based media (right).

Cells are damaged by hydrogen peroxide (H2O2) and other reactive oxygen species (ROS) produced during metabolism. In the brain, such damage contributes to neurodegenerative diseases. However, neurons are protected from damage by astroglial cells, which detoxify H2O2, but the underlying protective mechanism has remained unclear. In Carbohydrate Research, Ivan Spasojevic acute et al. now propose that fructose may have a locally protective antioxidant role in helping astroglial cells to counteract oxidative stress.

Oxidative damage in cells is detected by redox-sensitive transcription factors that initiate protective mechanisms such as an inflammatory response to infection. With age, oxidative damage increases as more ROS leak from the mitochondria, and physiological damage responses can be transformed into persistent disease states. Antioxidants convert ROS into harmless substances. However, despite the link between ROS and ageing, dietary antioxidant supplements have not been shown to prolong life unless the general diet is poor. It is thought that the body does not allow exogenous antioxidants to swamp a cell's ability to detect acute oxidative damage, maintaining instead a tight regulation of redox states by precluding antioxidants from entering the cell. Nevertheless, antioxidants that are able to enter a cell can protect it from damage.

Having recently discovered that fructose has antioxidant capacity in vitro, Spasojevic acute et al. investigated whether it can protect astroglial cells exposed to H2O2. In comparison with glucose, fructose prevented pro-oxidative changes in the cells. Cells cultured in glucose alone had lower viability after H2O2 treatment than those cultured with fructose or a mixture of the two sugars. Some phosphorylated derivatives of fructose had a greater effect, with fructose 1,6-bisphosphate (FBP) affording the most protection against oxidative changes.

The production of dangerous hydroxyl radicals from H2O2 is catalyzed by iron through the Fenton mechanism. Although Spasojevic acute et al. found that glucose and fructose have similar hydroxyl-scavenging abilities, they hypothesized that the greater protective effect of fructose might stem from its ability to sequester iron. The iron-fructose complex would interact with H2O2 to degrade fructose into glycolate, and the hydroxyl radical would not be produced. In vitro, the phosphorylated derivatives of fructose — FBP, fructose 1-phosphate (F1P) and fructose 6-phosphate (F6P) — were all more efficient than fructose itself at both hydroxyl-radical scavenging and iron sequestration. Nevertheless, the authors found that in contrast to FBP and F1P, F6P did not provide any protection to astroglial cells in vivo. F6P, unlike the other fructose metabolites, is not transported by the dicarboxylate transporters found in brain cells, suggesting that its failure to protect cells in culture arises from a difficulty in entering the cells.

Whereas homeostatic mechanisms prevent antioxidants in the blood from breaching cellular membranes, the authors propose that fructose and its phosphorylated forms are less likely to be excluded from cells because they are cellular energy sources. Although the long-term consumption of large amounts of fructose would be highly inadvisable because of its links to cardiovascular disease and obesity, these data suggest that acute administration of fructose or FBP might be therapeutically useful in limiting oxidative damage in neurological disease.

Emma Leah

Original research papers:

  1. Spasojevic acute et al. Protective role of fructose in the metabolism of astroglial C6 cells exposed to hydrogen peroxide. Carbohydrate Res. (3 June 2009) doi: 10.1016/j.carres.2009.05.023 | Article |
  2. Spasojevic acute et al. Relevance of the capacity of phosphorylated fructose to scavenge the hydroxyl radical. Carbohydrate Res. 344, 80–84 (2008) doi: 10.1016/j.carres.2008.09.025 | Article |.