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Free Oxygen Radicals

Free Oxygen Radicals, sometimes called reactive oxygen species, are unstable molecules that are often produced in wounds. These molecules are filled with unpaired electrons, making them extremely reactive; they aggressively seek out other molecules, in an effort to steal their electrons, thus creating more radicals, and perpetuating the cycle. Eventually, these radicals begin attacking healthy tissue that surrounds an injury, making the wound more severe, and slowing the healing process. Researchers at the Institute for Macromolecular Chemistry at the Academy of Science have developed a unique neutralizing compound, to prevent the perpetuation of free oxygen radicals. This polymer compound, the active ingredient in the over the counter moist healing gel Wound-Be-Gone®, uses a method of binding oxygen radicals; this binding process, called redox, or oxidation-reduction process, uses active amino groups to react with the radicals, binding them, and prohibiting them from creating more radicals. Wound-Be-Gone®, a protective gel that is applied directly to wounds such as abrasions, surgical incisions and skin ulcers, is the only product on the market today that contains this specialized technology.

 

Oxidative Stress

Introduction

The paradox of aerobic life, or the “Oxygen Paradox,” is that higher eukaryotic aerobic organisms cannot exist without oxygen, yet oxygen is inherently dangerous to their existence. This ‘dark side’ of oxygen relates directly to the fact that the electron configuration of an oxygen atom is 1s22s22p4 and, consequently, each oxygen atom has two unpaired electrons in its outer valence shell. Thus atomic oxygen is a free radical. Reduction of oxygen by the mitochondrial electron-transport chain, to produce water, is considered to be a relatively safe process; however, the reduction of oxygen generates reactive intermediates known as reactive oxygen species. The reductive environment of the cellular milieu provides ample opportunities for oxygen to undergo unscheduled reduction. Thus, the superoxide anion radical, hydrogen peroxide and the extremely reactive hydroxyl radical are common products of life in an aerobic environment, and these agents appear to be responsible for oxygen toxicity. To survive in such an unfriendly oxygen environment, living organisms generate a variety of antioxidant compounds. Additionally, a series of antioxidant enzymes, the role of which is to trap and inactivate reactive oxygen intermediates, also known as reactive oxygen species (ROS) is synthesized by all known aerobic organisms. Although extremely important, the antioxidant enzymes and compounds are not completely effective in preventing oxidative damage. To deal with the damage that does still occur, a series of damage removal/repair enzymes, for proteins, lipids and DNA, is synthesized. Finally, since oxidative stress levels may vary from time to time, organisms are able to adapt to such fluctuating stresses by inducing the synthesis of antioxidant enzymes and damage removal/repair enzymes. In a perfect world the story would end here; unfortunately, biology is seldom so precise. The reality appears to be that, despite the valiant antioxidant and repair mechanisms described above, oxidative damage remains an inescapable outcome of aerobic existence. In recent years oxidative stress has been implicated in a wide variety of degenerative processes, diseases and syndromes, including the following: mutagenesis, cell transformation and cancer; atherosclerosis, arteriosclerosis, heart attacks, strokes and ischemia/reperfusion injury; chronic inflammatory diseases, such as rheumatoid arthritis, lupus erythematosus and psoriatic arthritis; acute inflammatory problems, such as wound healing; photo-oxidative stresses to the eye, such as cataract; central-nervous-system disorders, such as certain forms of familial amyotrophic lateral sclerosis, certain glutathione peroxidase-linked adolescent seizures, Parkinson’s disease and Alzheimer’s dementia; and a wide variety of age-related disorders, perhaps even including factors underlying the aging process itself. Some of these oxidation-linked diseases or disorders can be exacerbated, perhaps even initiated, by numerous environmental pro-oxidants and/or pro-oxidant drugs and foods. Alternatively, compounds found in certain foods may be able to significantly bolster biological resistance against oxidants. Currently, great interest centers on the possible protective value of a wide variety of plant-derived antioxidant compounds, particularly those from fruits and vegetables. A role for sterically hindered amines in scavenging free radicals Sterically hindered amines (2,2,6,6-tetramethyl-substituted piperidines) are chemical compounds easily oxidized by electron transfer to parent cations in n-butyl chloride solution, by sulfate radical anions in aqueous solution, and by sensitized electron transfer to carbonyl triplets. In nonpolar surroundings, the radical cations of the tertiary piperidines have been directly observed by optical spectroscopy to exhibit absorption maxima below λ = 300 nm and around 550 nm. This occurs in the time span of nanoseconds. Subsequently, these sterically hindered amines deprotonate to α-alkylamine radicals which are also the first observable products of oxidation with sulfate radical anions in water. In the case of secondary piperidines, the amine radical cations deprotonate to aminyl radicals in times < 10 ns. The triplet-sensitized electron transfer to the benzophenone as well as cyclohexanone triplet results in amine-derived and ketyl-type radicals formed at a nearly diffusion-controlled rate, which suggests an electron- and subsequent proton-transfer mechanism. In the presence of oxygen, the amine-derived radicals are oxidized to nitroxyl radicals by different pathways for secondary and tertiary piperidines. For the reaction of the nitroxyl radicals with other radicals, rate constants are found to be quite similar (about 5 × 108 M-1 s-1 ) for several alkyl radicals and for the tert-butyloxyl radical and less than 105 M-1 s-1 for alkylperoxyl radicals. Because of the minor importance of radical reactions with the sterically hindered amines, the antioxidant effects of these compounds may be explainable by oxidation, primarily via cationic and subsequently radical intermediates to the persistent nitroxyl radicals, which scavenge free radicals very efficiently.

A role for sterically hindered amines in wound healing
In summary, it is useful to think of ROS as toxic waste products which produce oxidative stress during the inflammatory phase of wound healing. ROS result from the respiratory burst associated with revascularization, reperfusion and restructuring epithelial and connective tissues. The enzyme ribosomal S6 kinase (RSK) protects against excessive production of ROS. Overactivity of RSK from excessive production of ROS has been implicated in poor wound healing. Because sterically hindered amines are known to bind ROS, the topical administration of a hydrophilic 2-hydroxyethyl methacrylate polymer containing a mixture of sterically hindered amines is thought to function as an ROS scavenger, promote healing and inhibit scarring in cutaneous wounds. The ROS scavenging polymer (Wound-Be-Gone, Wake Pharma US Inc) is purported to decrease inflammation in the absence of topical antibiotic suggesting that healing of cutaneous wounds may be improved by the topical administration of this polymer.

clinical-study-results

Article by Wake Pharma USA