THE OXIDANT AND ANTIOXIDANT BALANCE IN WOUNDS

University Of California San Francisco, San Francisco CA

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Abstract

It is the objective of this research to decrease surgical and traumatic wound infection in humans, develop explanations for depressed wound repair and infections in diabetics and provide a comprehensive assessment of the oxidant/antioxidant state of wound tissue. Wound healing is impaired by infections due to bacteria which are more prevalent under conditions where the leukocyte production of reactive oxygen species (ROS) is decreased. Patients who develop post-operative surgical infections have a profile of bacterial infection that is similar to patients with chronic granulomatous disease (CGD). As CGD is characterized by a defective oxidative burst, the role of superoxide production becomes crucial in controlling bacterial infections. In conditions where the respiratory burst is compromised, surgical infections become more likely. The leukocyte response to trauma and infection must balance between the number and state of leukocytes infusing into the wound area, the availability of oxygen for an oxidative burst and the antioxidant capabilities of the leukocytes and surrounding cells. The ability of leukocytes to protect themselves from their own oxidative burst requires a potent antioxidant defense. This proposed work will characterize the antioxidant defenses of neutrophils against radical oxidants and determine how the neutrophil can protect itself against its own oxidative burst. It is planned to evaluate the neutrophil antioxidant defense in diabetic rats and humans by measuring the ability of the neutrophil to fight infection, develop strategies to improve bactericidal activity by modulating the oxidant/antioxidant balance and determine if excel infiltration of activated neutrophils to a wound site can decrease bactericidal activity due to excessive hypoxia. Methods include measurement of O2 consumption, O2-production and HPLC analysis of numerous water and lipid soluble antioxidants using both rat and human samples. Diabetic and normal rats will be fed diets to adjust their antioxidants. It is the goal of this work to provide a basis for practical new ways to improve wound healing.