"Reducing Sugars"/Polyol Pathway and NADPH oxidase

Here's an article that sheds some light on the way "reducing sugars," sugars, such as ribose and xylitol, that increase the metabolic flux through the nonoxidative pentose cycle, could produce glutathione depletion and increase reactive oxygen species. This would occur especially in the context of diminished mitochondrial functioning. One mechanism linking the activities of NADPH oxidases to the lactate/pyruvate ratio and the cytoplasmic NADH/NAD+ ratio is just that an elevated NADH/NAD+ ratio, such as occurs in response to xylitol (see previous posts for reference), would provide more NADH as a substrate to NADPH oxidases ("NAD(P)H oxidase" is a generic phrase and usually refers to bactericidal NADPH oxidase enzymes in neutrophils, but a wide variety of enzyme complexes and enzymes can have NADPH oxidase activity and generate large amounts of superoxide) and thereby produce an increase in superoxide production and, consequently, peroxynitrite production and glutathione depletion:

http://www.ncbi.nlm.nih.gov/pubmed/16733230

I collected some other papers that show the same increases in NADPH oxidase activity in response to an increase in the cytosolic NADH/NAD+ ratio, but the consequences of that wouldn't always be bad. There wouldn't necessarily be a net increase in oxidative stress, and some research shows that ribose actually reduces malionaldehyde production in skeletal muscles and reduces the loss of glutathione, into the blood, in response to exercise. So the potential for detrimental effects due to these effects would be cell-type and cell-context-specific. During post-ischemic reperfusion, this could be detrimental, if one did not take measures to reduce NADPH oxidase activity or reduce the consequences of its activation. Uric acid can reduce NADPH oxidase activity and buffer glutathione levels, and so on.