Hydrophilic Dual Vitamin E-Like Antioxidants as Modulators of Inflammatory Response in Low-Flow States and Impaired Wound Healing

Hydrophilic 2,3-dihydro-5-hydroxy-2-benzofuranacetic acids were designed to maximize the antioxidants potency of phenols and are also chemically related to α-tocopherol. Besides quenching free radicals and blocking the chain breaking reaction, these compounds may act as modulators of the inflammatory cascade triggered by oxidative stress. In fact they block the activation of Nuclear Factor Kappa B (NF-kB) induced by okadaik acid, H2O2, phorbol ester, ceramide and LPS. In addition, in vivo they reduce the inflammatory response reaction and display a marked protection in hemorrhagic shock, septic shock, and myocardial ischemia-reperfusion injury. The persistence of the inflammatory phase has detrimental consequences for the process of wound repair. Increased lipid peroxidation has been shown to play an important role in the wound healing disorders of diabetes: indeed it may prolong the inflammatory phase and significantly alter the mechanisms of angiogenesis. Hydrophilic dual vitamin E-like antioxidants have the capacity to modulate the inflammatory phase and to improve the altered angiogenesis therefore suggesting a possible role in the management of diabetic foot ulcer.