Abstract
Advertisements targeted at the elderly population suggest that antioxidant therapy will reduce free radicals and promote wound healing, yet few scientific studies substantiate these claims. To better understand the potential utility of supplemental antioxidant therapy for wound healing, we tested the hypothesis that age and tissue ischemia alter the balance of endogenous antioxidant enzymes. Using a bipedicled skin flap model, ischemic and non-ischemic wounds were created on young and aged rats. Wound closure and the balance of the critical antioxidants superoxide dismutase and glutathione in the wound bed were determined. Ischemia delayed wound closure significantly more in aged rats. Lower superoxide dismutase 2 and glutathione in non-ischemic wounds of aged rats indicate a basal deficit due to age alone. Ischemic wounds from aged rats had lower superoxide dismutase 2 protein and activity initially, coupled with decreased ratios of reduced/oxidized glutathione and lower glutathione peroxidase activity. De novo glutathione synthesis, to restore redox balance in aged ischemic wounds, was initiated as evidenced by increased glutamate cysteine ligase. Results demonstrate deficiencies in two antioxidant pathways in aged rats that become exaggerated in ischemic tissue, culminating in profoundly impaired wound healing and prolonged inflammation.
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Acknowledgments
This work was supported by a Veteran’s Affairs Merit Award (BX09-002) to L. Gould. The authors would like to thank the University of South Florida Pathology Core Facility for the preparation of histological specimens. The authors declare no conflicts of interest for this work.
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Representative H&E staining of days 10, 14, and 21 non-ischemic (a–c young; d–f aged) wounds at 4× power and 40× insets (n = 3–4 sections/group/time point). TE thickened epidermis. Scale bars = 500 μm and 50 μM (insets; JPEG 212 kb)
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Moor, A.N., Tummel, E., Prather, J.L. et al. Consequences of age on ischemic wound healing in rats: altered antioxidant activity and delayed wound closure. AGE 36, 733–748 (2014). https://doi.org/10.1007/s11357-014-9617-4
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DOI: https://doi.org/10.1007/s11357-014-9617-4