Locally Delivered Adenosine and Glutathione Improve Fibroblast Proliferation and Collagen Production
Main Article Content
Abstract
Diabetic foot ulcers are particularly difficult to treat due to neuropathy and healing deficiencies. Glutathione and adenosine have been studied as possible modulators of diabetic response and would healing. The objective of this in vitro study was to measure the effects of adenosine and glutathione on fibroblast proliferation and collagen synthesis. Further, methods were explored for delivering these compounds locally through chitosan sponges. Elution concentrations of adenosine and glutathione from chitosan sponges were evaluated through HPLC, and activity was evaluated for fibroblast proliferation and viability in vitro. Furthermore, collagen production of normal and hyperglycemic fibroblasts exposed to those compounds individually and in combination was evaluated using a colorimetric collagen assay. Results indicate a dose-dependent increase in fibroblast proliferation, with exposure to concentrations up to 133.6 mg/ml adenosine and 76.8 mg/ml glutathione. Total collagen concentration determination confirmed that adenosine alone at 133.6 mg/ml significantly increases collagen production in low glucose conditions, but not to the same extent in medium and diabetic glucose conditions. Glutathione at 76.8 mg/ml did not increase collagen production compared to control or adenosine alone, and the combination attenuated increases in collagen production in low glucose conditions. There were no additive or synergistic effects of combining these two small molecule mediators of growth on fibroblast growth or collagen production. Both adenosine and glutathione were released in a burst response from chitosan sponges, and demonstrated activity in increasing proliferation. These preliminary in vitro evaluations demonstrate that the local delivery of adenosine and glutathione released from chitosan sponges may be a promising strategy for the treatment of diabetic foot ulcers under glucose conditions that are closely managed.
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JENNINGS, Jessica Amber.
Locally Delivered Adenosine and Glutathione Improve Fibroblast Proliferation and Collagen Production.
Biomedical Engineering Review, [S.l.], n. 2, june 2015.
ISSN 2375-9151.
Available at: <https://esmed.org/MRA/bme/article/view/167>. Date accessed: 16 apr. 2024.
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Liu, Z. J., and O. C. Velazquez. 2008. Hyperoxia, endothelial progenitor cell mobilization, and diabetic wound healing. Antioxidants & redox signaling 10 (11):1869-82. http://www.ncbi.nlm.nih.gov/pubmed/18627349.
Lu, S., W. Gao, and H. Y. Gu. 2008. Construction, application and biosafety of silver nanocrystalline chitosan wound dressing. Burns : journal of the International Society for Burn Injuries 34 (5):623-8. http://www.ncbi.nlm.nih.gov/pubmed/18226459.
Ma, C., M. A. Hernandez, V. E. Kirkpatrick, L. J. Liang, A. L. Nouvong, and Gordon, II. 2015. Topical Platelet-Derived Growth Factor vs Placebo Therapy of Diabetic Foot Ulcers Offloaded With Windowed Casts: A Randomized, Controlled Trial. Wounds : a compendium of clinical research and practice 27 (4):83-91. http://www.ncbi.nlm.nih.gov/pubmed/25855851.
Marcelo, C., M. Deveci, R. Gilmont, W. Dunham, B. Mudge, and D. Smith. 2001. Glutathione treatment accelerates diabetic wound healing. Journal of Investigative Dermatology 117 (2):420-420.
Montesinos, M. C., A. Desai, J. F. Chen, H. Yee, M. A. Schwarzschild, J. S. Fink, and B. N. Cronstein. 2002. Adenosine promotes wound healing and mediates angiogenesis in response to tissue injury via occupancy of A(2A) receptors. The American journal of pathology 160 (6):2009-18. http://www.ncbi.nlm.nih.gov/pubmed/12057906.
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