Relevance of the capacity of phosphorylated fructose to scavenge the hydroxyl radical

The hydroxyl radical ((OH)-O-center dot) has detrimental biological activity due to its very high reactivity. Our experiments were designed to determine the effects of equimolar concentrations of glucose, fructose and mannitol and three phosphorylated forms of fructose (fructose-1-phosphate (F1P): fructose-6-phosphate (F6P): and fructose-1,6-bis(phosphate) (F16BP)) on (OH)-O-center dot radical production via the Fenton reaction. EPR spectroscopy using spin-trap DEPMPO was applied to detect radical production. We found that the percentage inhibition of (OH)-O-center dot radical formation decreased in the order F16BP > F1P > F6P > fructose > mannitol = glucose. As ketoses can sequester redox-active iron thus preventing the Fenton reaction, the Haber-Weiss-like system was also employed to generate (OH)-O-center dot, so that the effect of iron sequestration could be distinguished from direct (OH)-O-center dot radical scavenging. In the latter system, the rank order of (OH)-O-center dot scavenging activity was F16BP > F1P > F6P > fructose = mannitol = glucose. Our results clearly demonstrate that intracellular phosphorylated forms of fructose have more scavenging properties than fructose or glucose, leading us to conclude that the acute administration of fructose could overcome the body's reaction to exogenous antioxidants during appropriate therapy in certain pathophysiological conditions related to oxidative stress, Such as sepsis, neurodegenerative diseases, atherosclerosis, malignancy, and some complications of pregnancy. (C) 2008 Elsevier Ltd. All rights reserved.