Folic Acid as a Fenton-modulator: Possible Physiological Implication

Acting as a redox switch, folic acid (1) might be a promising iron modulator to protect cellular machinery against oxidative stress and iron overload. The vitamin 1 can directly control the iron concentration by oxidizing it even if present in chelated forms. In addition, during its role as a reducing agent for the biologically relevant reactive oxygen species (ROS), it furnishes 6-formyl pterin. This folate-derived intermediate possesses a stronger Fe2+-oxidizing capacity than 1. Thus, compound 1 can reduce the iron toxicity in two ways. Although, the Fe2+-oxidizing capacity is nullified in the presence of a strong biological reductant like ascorbic acid, this property may play a predominant role during pathogenesis when the cellular ascorbic acid levels deplete significantly. The iron-modulatory property of 1 was also confirmed with the L929 mouse fibroblast cell line.