Vascular Endothelial Growth Factor Supplementation Enhance Skin Antioxidant Capacity in Hyperglycemic Rats
Year 2023,
Volume: 36 Issue: 4, 1449 - 1461, 01.12.2023
Ebru Uzun
,
Doç. Dr. Barbaros Balabanlı
,
Şule Coşkun Cevher
Abstract
The fundamental reasons for delayed wound healing in diabetic animals include inadequate production of growth factors or their increased devastation. Vascular Growth Factor (VEGF) has a biological role in the healing process of mucosal and skin wounds, especially in the process of new vessel formation. We planned to examine the oxidant-antioxidant events that occur during healing with topical VEGF application in diabetic rats. Experiments were performed 36 adults female Wistar albino rat diabetes induced by streptozotocin. The incisional wounds were made on the dorsal region in the rats. Rats were separated to 3 groups: the untreated (negative control) group (n=12), the chitosan group (n=12), the chitosan + VEGF group (n=12). The treatments were continued for 3 and 7 days, excluding the control and negative control groups. Then, the animals were sacrificed on the 3rd and 7th days of wound healing. Antioxidant and oxidant parameters in skin tissue were measured using biochemical methods. Topical VEGF application was decreased the NOx levels on the 3rd day compared to other groups. Moreover, it increased wound tissue GSH and AA levels, subsequently contributing to the enhance tissue antioxidant capacity. In conclusion, VEGF application increases the antioxidant capacity of the tissue and simultaneously reduces the oxidative stress and thus gives a positive acceleration to the wound healing process.
Supporting Institution
Gazi University's Scientific Investigation Projects (BAP)
Project Number
05/2011-01
Thanks
This investigation was supported by Gazi University Department of Projects of Scientific Investigation, Ankara, Turkey
References
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- [26] Brown, N.J., Smyth, E.A.E., Cross, S.S., and Reed, M.W., “Angiogenesis induction and regression in human surgical wounds”, Wound Repair and Regeneration, 10: 245-251, (2002).
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- [30] Losi, P., Briganti, E., Errico, C., Lisella, A., Sanguinetti, E., Chiellini, F., and Soldani, G., “Fibrin-based scaffold incorporating VEGF- and bFGF-loaded nanoparticles stimulates wound healing in diabetic mice”, Acta Biomaterialia, 9(8): 7814-782, (2013).
- [31] Kirchner, L.M., Meerbaum, S.O., Gruber, B.S., Knoll, A.K., Bulgrin, J., Taylor, R.A., and Schmidt, S.P., “Effects of vascular endothelial growth factor on wound closure rates in the genetically diabetic mouse model”, Wound Repair and Regeneration, 11: 127-131, (2003).
- [32] Elçin, Y.M., Dixit, V., and Gitnick, G., “Extensive in vivo angiogenesis following controlled release of human vascular endothelial cell growth factor: implications for tissue engineering and wound healing”, Artificial Organs, 25(7): 558-565, (2001).
- [33] Infanger, M., Shakibaei, M., Kossmehl, P., Hollenberg, S.M., Grosse, J., Faramarzi, S., Schulze-Tanzil, G., Paul, M., and Grimm, D., “Intraluminal application of vascular endothelial growth factor enhances healing of microvascular anastomosis in a rat model”, Journal of Vascular Research, 42(3): 202-213, (2005).
- [34] Gökşen, S., Balabanlı, B., and Coşkun-Cevher, Ş., “Application of platelet derived growth factor-BB and diabetic wound healing: the relationship with oxidative events”, Free Radical Research, 51(5), 498-505, (2017).
- [35] Miranda, K.M., Espey, M.G., and Wink, D.A., “A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite”, Nitric Oxide, 5(1): 62-71, (2001).
- [36] Casini, A.F., Ferrali, M., Pompella, A., Maellaro, E., and Comporti, M., “Lipid peroxidation and cellular damage in extrahepatic tissues of bromobenzene-intoxicated mice”, The American Journal of Pathology, 123(3): 520-53, (1986).
- [37] Aykaç, G., Uysal, M., Yalçın, A.S., Koçak Toker, N., Sivas, A., and Öz, H., “The effect of chronic ethanol ingestion on hepatic lipid peroxide, glutathione, glutathione peroxidase and glutathione transferase in rats”, Toxicology, 36(1): 71-76, (1985).
- [38] Berger, J., Shepard, D., Morrow, F., and Taylor, A., “Relationship between dietary intake and tissue levels of reduced and total vitamin C in the nonscorbutic guinea pig”, Journal of Nutrition, 119(5): 734-740, (1989).
- [39] Sun, Y., Oberley, L.W., and Li, Y., “A simple method for clinical assay of super oxide dismutase”, Clinical Chemistry, 34(3): 497-500, (1988).
- [40] Hwang, S.M., Chen, C.Y., Chen, S.S., and Chen, J.C., “Chitinous materials inhibit nitric oxide production by activated RAW 264.7 macrophages”, Biochemical and Biophysical Research Communications, 271(1): 229-233, (2000).
- [41] Di, G., Zhao, X., Qi, X., Zhang, S., Feng, L., Shi, W., and Zhou, Q., “VEGF-B promotes recovery of corneal innervations and trophic functions in diabetic mice”, Scientific Reports, 7(1): 1-13, (2017).
- [42] Kalay, Z., and Cevher, S. C., “Oxidant and antioxidant events during epidermal growth factor therapy to cutaneous wound healing in rats”, International Wound Journal, 9(4): 362-371, (2012).
- [43] Judith, R., Nithya, M., Rose, C., and Mandal, A. B., “Application of a PDGF-containing novel gel for cutaneous wound healing”, Life Sciences, 87(1-2): 1-8, (2010).
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- [45] Rasik, A.M., and Shukla, A., “Antioxidant status in delayed healing type of wounds”, International Journal of Experimental Pathology, 81(4): 257-263, (2000).
- [46] Aykaç, G., Uysal, M., Yalçin, A. S., Koçak-Toker, N., Sivas, A., and Öz, H., “The effect of chronic ethanol ingestion on hepatic lipid peroxide, glutathione, glutathione peroxidase and glutathione transferase in rats”, Toxicology, 36(1): 71-76, (1985).
- [47] Arjunan, P., Lin, X., Tang, Z., Du, Y., Kumar, A., Liu, L., and Li, X., “VEGF-B is a potent antioxidant”, Proceedings of the National Academy of Sciences, 115(41): 10351-10356, (2018).
- [48] Chen, R., Lee, C., Lin, X., Zhao, C., and Li, X., “Novel function of VEGF-B as an antioxidant and therapeutic implications”, Pharmacological Research, 143: 33-39, (2019).
- [49] Langston, W., Chidlow, JH Jr., Booth, BA., Barlow, SC., Lefer, DJ., Patel, R.P., and Kevil, CG., “Regulation of endothelial glutathione by ICAM-1 governs VEGF-A-mediated eNOS activity and angiogenesis”, Free Radical Biology and Medicine, 42(5): 720-729, (2007).
- [50] Li, Y., and Schellhorn, H. E., “New developments and novel therapeutic perspectives for vitamin C. The Journal of Nutrition”, 137(10):2171-2184, (2007).
- [51] Srivatsan, R., Das, S., Gadde, R., Manoj, K. K., Taduri, S., Rao, N., and Rao, A., “Antioxidants and lipid peroxidation status in diabetic patients with and without complications”, Scientific Information Database, 121-127, (2009).
- [52] Güleç Peker, E. G., Coşkun, Ş., Ebegil, M., and Acartürk, F., “Effect of exogenous epidermal growth factor (EGF) on nonenzymatic antioxidant capacities and MPO activity of wound tissue”, Medicinal Chemistry Research, 19(6): 533-540, (2010).
- [53] Arya, A. K., Pokharia, D., and Tripathi, K., “Relationship between oxidative stress and apoptotic markers in lymphocytes of diabetic patients with chronic non healing wound”, Diabetes Research and Clinical Practice, 94(3): 377-384, (2011).
Year 2023,
Volume: 36 Issue: 4, 1449 - 1461, 01.12.2023
Ebru Uzun
,
Doç. Dr. Barbaros Balabanlı
,
Şule Coşkun Cevher
Project Number
05/2011-01
References
- [1] Schilling, J.A., “Wound healing”, Surgical Clinics of North America, 56(4): 859-874, (1976).
- [2] Martin, P., “Wound healing--aiming for perfect skin regeneration”, Science, 276(5309): 75-81, (1997).
- [3] Singer, A.J., and Clark, R.A., “Cutaneous wound healing”, The New England Journal of Medicine, 341: 741-786, (1999).
- [4] Hom, D.B., “Wound healing in relation to scarring”, Facial Plastic Surgery Clinics of North America, 6:11, (1998).
- [5] Gantwerker, E.A., and Hom, D.B., “Skin: histology and physiology of wound healing”, Facial Plastic Surgery Clinics of North America, 19: 441-453, (2011).
- [6] Wilgus, T.A., Ferreira, A.M., Oberyszyn, T.M., Bergdall, V.K., and Dipietro, L.A., “Regulation of scar formation by vascular endothelial growth factor”, Laboratory Investigation, 88: 579-590, (2008).
- [7] Chang M., and Nguyen T.T., “Strategy for Treatment of Infected Diabetic Foot Ulcers”, Accounts of chemical research, 54(5): 1080-1093, (2021).
- [8] Li, H., Fu, X., Zhang, L., Huang, Q., Wu, Z., and Sun, T., “Research of PDGF-BB gel on the wound healing of diabetic rats and its pharmacodynamiccs”, The Journal of Surgical Research, 145: 41-48, (2008).
- [9] Vincent, A.M., Russell, J.W., Low, P., and Feldman, E.L., “Oxidative stress in the pathogenesis of diabetic neuropathy”, Endocrine Reviews, 25: 612-628, (2004).
- [10] Memişoğulları, R., Taysi, S., Bakan, E., and Çapoğlu, I., “Antioxidant status and lipid peroxidation in type II diabetes mellitus”, Cell Biochemistry and Function, 21: 291-296, (2003).
- [11] Cherubini, A., Ruggiero, C., Polidori, M.C., and Mecocci, C., “Potential markers of oxidative stress in stroke”, Free Radical Biology and Medicine, 39: 841-852, (2005).
- [12] Memişoğulları, R., Bakan, E., “Levels of ceruloplasmin, transferrin, and lipid peroxidation in the serum of patients with Type 2 diabetes mellitus”, Journal of Diabetes and Its Complications, 18: 193-197, (2004).
- [13] Chen S.K., Tsai M.L., Huang J.R., and Chen R.H., “In vitro antioxidant activities of low-molecular-weight polysaccharides with various functional groups”, Journal of Agricultural and Food Chemistry, 57(4):2699–2704, (2009).
- [14] Ishihara, M., Ono, K., Sato, M., Nakanishi, K., Saito, Y., Yura, H., and Kurita, A., “Acceleration of wound contraction and healing with a photocrosslinkable chitosan hydrogel”, Wound Repair and Regeneration, 9(6), 513-521, (2001).
- [15] Ueno, H., Mori, T., and Fujinaga, T., “Topical formulations and wound healing applications of chitosan”, Advanced Drug Delivery Reviews, 52(2), 105-115, (2001).
- [16] Kaltalioglu, K., Coskun-Cevher, S., Tugcu-Demiroz, F., and Celebi, N., “PDGF supplementation alters oxidative events in wound healing process: a time course study”, Archives of Dermatological Research, 305(5), 415-422, (2013).
- [17] Alemdaroğlu C., Değim Z., Celebi N., Zor F., Oztürk S., and Erdoğan D., “An investigation on burn wound healing in rats with chitosan gel formulation containing epidermal growth factor”, Burns, 32(3):319–327, (2006).
- [18] Cevher, Ş.C., and Çoban, V. S., “The Investigation of the Effect of Topical Vascular Endothelial Growth Factor (VEGF) Administration On Serum Oxidative Parameters in Diabetic Rats”, Gazi University Journal of Science, 29(3), 543-547, (2016).
- [19] Barrientos, S., Stojadinovic, O., Golinko, M.S., Brem, H. and Tomic, C.M., “Growth factors and cytokines in wound healing”, Wound Repair and Regeneration, 16(5): 585-601, (2008).
- [20] Yazır, Y., Gonca, S., Filiz, S., and Dalçık, H., “An important protein family for endothelial cells; vascular endothelial growth factor (Vegf) members of the family, structure and synthesis”, Cumhuriyet Medical Journal, 26(4): 181-184, (2004).
- [21] Vincenti, V., Cassano, C., Rocchi, M., and Persico, G., “Assignment of the vascular endothelial growth factor gene to human chromosome 6p21.3”, Circulation, 93: 1493-1495, (1996).
- [22] Erol, N., “Vascular endothelial growth factor and anti-vegf agents”, Journal of Retina Vitreous, 15: 35-40, (2007).
- [23] Ferrara, N., Gerber, H.P., and Le Couter, J., “The biology of VEGF and its receptors”, Nature Medicine, 9: 669-676, (2003).
- [24] Nissen, N.N., Polverini, P.J., Koch, A.E., Volin, M.E., Gamelli, R.L., and DiPietro, L.A., “Vascular endothelial growth factor mediates angiogenic activity during the proliferative phase of wound healing”, The American Journal of Pathology, 152: 1445-1452, (1998).
- [25] Brown, L.F., Yeo, K.T., Berse, B., Yeo, T.K., Senger, D.R., Dvorak, H.F., and Van de Water, L., “Expression of vascular permeability factor by epidermal keratinocytes during wound healing”, Journal of Experimental Medicine, 176: 1375-1379, (1992).
- [26] Brown, N.J., Smyth, E.A.E., Cross, S.S., and Reed, M.W., “Angiogenesis induction and regression in human surgical wounds”, Wound Repair and Regeneration, 10: 245-251, (2002).
- [27] Nissen, N.N., Polverini, P.J., Gamelli, R.L., and DiPietro, L.A., “Basic fibroblast growth factor mediates angiogenic activity in early surgical wounds”, Surgery, 119: 457-465, (1996).
- [28] Hopf, H.W., Gibson, J.J., Angeles, A.P., Constant, J.S., Feng, J.J., Rollins, M.D., Zamirul Hussain, M., and Hunt, T.K., “Hyperoxia and angiogenesis”, Wound Repair and Regeneration, 13: 558-564, (2005).
- [29] Bitto, A., Minutoli, L., Altavilla, D., Polito, F., Fiumara, T., Marini, H., Galeano, M., Calò, M., Lo Cascio, P., Bonaiuto, M., Migliorato, A., Caputi, A.P., and Squadrito, F., “Simvastatin enhances VEGF production and ameliorates impaired wound healing in experimental diabetes”, Pharmacological Research, 57(2): 159-169, (2008).
- [30] Losi, P., Briganti, E., Errico, C., Lisella, A., Sanguinetti, E., Chiellini, F., and Soldani, G., “Fibrin-based scaffold incorporating VEGF- and bFGF-loaded nanoparticles stimulates wound healing in diabetic mice”, Acta Biomaterialia, 9(8): 7814-782, (2013).
- [31] Kirchner, L.M., Meerbaum, S.O., Gruber, B.S., Knoll, A.K., Bulgrin, J., Taylor, R.A., and Schmidt, S.P., “Effects of vascular endothelial growth factor on wound closure rates in the genetically diabetic mouse model”, Wound Repair and Regeneration, 11: 127-131, (2003).
- [32] Elçin, Y.M., Dixit, V., and Gitnick, G., “Extensive in vivo angiogenesis following controlled release of human vascular endothelial cell growth factor: implications for tissue engineering and wound healing”, Artificial Organs, 25(7): 558-565, (2001).
- [33] Infanger, M., Shakibaei, M., Kossmehl, P., Hollenberg, S.M., Grosse, J., Faramarzi, S., Schulze-Tanzil, G., Paul, M., and Grimm, D., “Intraluminal application of vascular endothelial growth factor enhances healing of microvascular anastomosis in a rat model”, Journal of Vascular Research, 42(3): 202-213, (2005).
- [34] Gökşen, S., Balabanlı, B., and Coşkun-Cevher, Ş., “Application of platelet derived growth factor-BB and diabetic wound healing: the relationship with oxidative events”, Free Radical Research, 51(5), 498-505, (2017).
- [35] Miranda, K.M., Espey, M.G., and Wink, D.A., “A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite”, Nitric Oxide, 5(1): 62-71, (2001).
- [36] Casini, A.F., Ferrali, M., Pompella, A., Maellaro, E., and Comporti, M., “Lipid peroxidation and cellular damage in extrahepatic tissues of bromobenzene-intoxicated mice”, The American Journal of Pathology, 123(3): 520-53, (1986).
- [37] Aykaç, G., Uysal, M., Yalçın, A.S., Koçak Toker, N., Sivas, A., and Öz, H., “The effect of chronic ethanol ingestion on hepatic lipid peroxide, glutathione, glutathione peroxidase and glutathione transferase in rats”, Toxicology, 36(1): 71-76, (1985).
- [38] Berger, J., Shepard, D., Morrow, F., and Taylor, A., “Relationship between dietary intake and tissue levels of reduced and total vitamin C in the nonscorbutic guinea pig”, Journal of Nutrition, 119(5): 734-740, (1989).
- [39] Sun, Y., Oberley, L.W., and Li, Y., “A simple method for clinical assay of super oxide dismutase”, Clinical Chemistry, 34(3): 497-500, (1988).
- [40] Hwang, S.M., Chen, C.Y., Chen, S.S., and Chen, J.C., “Chitinous materials inhibit nitric oxide production by activated RAW 264.7 macrophages”, Biochemical and Biophysical Research Communications, 271(1): 229-233, (2000).
- [41] Di, G., Zhao, X., Qi, X., Zhang, S., Feng, L., Shi, W., and Zhou, Q., “VEGF-B promotes recovery of corneal innervations and trophic functions in diabetic mice”, Scientific Reports, 7(1): 1-13, (2017).
- [42] Kalay, Z., and Cevher, S. C., “Oxidant and antioxidant events during epidermal growth factor therapy to cutaneous wound healing in rats”, International Wound Journal, 9(4): 362-371, (2012).
- [43] Judith, R., Nithya, M., Rose, C., and Mandal, A. B., “Application of a PDGF-containing novel gel for cutaneous wound healing”, Life Sciences, 87(1-2): 1-8, (2010).
- [44] Sen, S., and Chakraborty R., “The Role of Antioxidants in Human Health. American Chemical Society, Oxidative Stress: Diagnostics, Prevention and Therapy”, American Chemical Society, 1-37, (2011).
- [45] Rasik, A.M., and Shukla, A., “Antioxidant status in delayed healing type of wounds”, International Journal of Experimental Pathology, 81(4): 257-263, (2000).
- [46] Aykaç, G., Uysal, M., Yalçin, A. S., Koçak-Toker, N., Sivas, A., and Öz, H., “The effect of chronic ethanol ingestion on hepatic lipid peroxide, glutathione, glutathione peroxidase and glutathione transferase in rats”, Toxicology, 36(1): 71-76, (1985).
- [47] Arjunan, P., Lin, X., Tang, Z., Du, Y., Kumar, A., Liu, L., and Li, X., “VEGF-B is a potent antioxidant”, Proceedings of the National Academy of Sciences, 115(41): 10351-10356, (2018).
- [48] Chen, R., Lee, C., Lin, X., Zhao, C., and Li, X., “Novel function of VEGF-B as an antioxidant and therapeutic implications”, Pharmacological Research, 143: 33-39, (2019).
- [49] Langston, W., Chidlow, JH Jr., Booth, BA., Barlow, SC., Lefer, DJ., Patel, R.P., and Kevil, CG., “Regulation of endothelial glutathione by ICAM-1 governs VEGF-A-mediated eNOS activity and angiogenesis”, Free Radical Biology and Medicine, 42(5): 720-729, (2007).
- [50] Li, Y., and Schellhorn, H. E., “New developments and novel therapeutic perspectives for vitamin C. The Journal of Nutrition”, 137(10):2171-2184, (2007).
- [51] Srivatsan, R., Das, S., Gadde, R., Manoj, K. K., Taduri, S., Rao, N., and Rao, A., “Antioxidants and lipid peroxidation status in diabetic patients with and without complications”, Scientific Information Database, 121-127, (2009).
- [52] Güleç Peker, E. G., Coşkun, Ş., Ebegil, M., and Acartürk, F., “Effect of exogenous epidermal growth factor (EGF) on nonenzymatic antioxidant capacities and MPO activity of wound tissue”, Medicinal Chemistry Research, 19(6): 533-540, (2010).
- [53] Arya, A. K., Pokharia, D., and Tripathi, K., “Relationship between oxidative stress and apoptotic markers in lymphocytes of diabetic patients with chronic non healing wound”, Diabetes Research and Clinical Practice, 94(3): 377-384, (2011).