DOI: http://dx.doi.org/10.18203/2320-6012.ijrms20221785

Influence of oxidative stress and effect of topical application of α-tocopherol on wound healing in a diabetic animal model

Amos T. Nyamadzawo, Junko Nishio, Toshiko Ogawa, Shinobu Okada

Abstract


Background: Understanding mechanisms involved in development of diabetes mellitus-associated ulcers is vital to pioneering alternative care approaches. This study aimed to establish effects of oxidative stress (OS) and α-tocopherol’s effect on diabetic wound healing.

Methods: Using two animal experimental designs surgical wounds were created in 4 groups of 9-week-old diabetic and non-diabetic rats. OS was induced through antioxidant enzyme inhibition. In experiment-1 wounds were allowed to heal. In experiment-2 varying concentrations of topical α-tocopherol and/or the ointment-base were administered to diabetic animal wounds. Intermittent comparison of wound morphology, histology and local and systemic OS parameters was done.

Results: Irrespective of diabetic state, OS was associated with delayed wound size reduction and poor granulation-tissue collagen deposition. Delayed and subdued local glutathione peroxidase activity in response to wounding and OS induction was more pronounced in diabetic animals. Diabetic animals also showed higher serum malondialdehyde levels regardless of OS induction. Topical application of α-tocopherol was associated with denser wound granulation tissue collagen deposition but could not affect serum malondialdehyde levels.

Conclusions: OS interferes with wound healing especially collagen deposition and the effect is more pronounced in a diabetic state. Topical α-tocopherol can improve collagen deposition in diabetic wounds but cannot counteract systemic OS, therefore combining systemic and local antioxidant supplementation has potential for use in DFU care.


Keywords


Oxidative-stress, α-tocopherol, Diabetic wound healing, Collagen deposition

Full Text:

PDF

References


Mavrogenis AF, Megaloikonomos PD, Antoniadou T, Igoumenou VG, Panagopoulos GN, Dimopoulos L, et al. Current concepts for the evaluation and management of diabetic foot ulcers. EFORT Open Rev. 2018;3(9):513-25.

Alexiadou K, Doupis J. Management of diabetic foot ulcers. Diabetes Ther. 2012;3(1):4.

Smith K, Collier A, Townsend EM, O'Donnell LE, Bal AM, Butcher J, et al. One step closer to understanding the role of bacteria in diabetic foot ulcers: characterising the microbiome of ulcers. BMC Microbiol. 2016;16:54.

Wolcott RD, Rumbaugh KP, James G, Schultz G, Phillips P, Yang Q, et al. Biofilm maturity studies indicate sharp debridement opens a time- dependent therapeutic window. J Wound Care. 2010;19(8):320-8.

Kavitha KV, Tiwari S, Purandare VB, Khedkar S, Bhosale SS, Unnikrishnan AG. Choice of wound care in diabetic foot ulcer: a practical approach. World J Diabet. 2014;5(4):546-56.

Aderibigbe BA, Buyana B. Alginate in wound dressings. Pharmaceutics. 2018;10(2):42.

Park JW, Hwang SR, Yoon IS. Advanced growth factor delivery systems in wound management and skin regeneration. Molecules (Basel, Switzerland). 2017;22(8):1259.

Balin AK, Pratt L. Dilute povidone-iodine solutions inhibit human skin fibroblast growth. Dermatol Surg. 2002;28(3):210-4.

Deng L, Du C, Song P, Chen T, Rui S, Armstrong DG, et al. The role of oxidative stress and antioxidants in diabetic wound healing. Oxid Med Cell Longev. 2021;2021:8852759.

Lutchmansingh FK, Hsu JW, Bennett FI, Badaloo AV, McFarlane-Anderson N, Gordon-Strachan GM, et al. Glutathione metabolism in type 2 diabetes and its relationship with microvascular complications and glycemia. PloS One. 2018;13(6):0198626.

Dhall S, Do DC, Garcia M, Kim J, Mirebrahim SH, Lyubovitsky J, et al. Generating and reversing chronic wounds in diabetic mice by manipulating wound redox parameters. J Diabetes Res. 2014;2014:562625.

Chopra DP, Flaxman BA. The effect of vitamin A on growth and differentiation of human keratinocytes in vitro. J Investigat Dermatol. 1975;64(1):19-22.

Kamimura M, Matsuzawa T. Percutaneous absorption of α-tocopheryl acetate. J Vitaminol. 1968;14(2):150-9.

Mizuguchi K. Senshoku Ho No Subete. 1st ed. Japan: Ishiyaku Publishers; 2021.

Mizuguchi Y. Liver biopsy in modern medicine. Intechopen; 2011.

Ying C. A convenient method for quantifying collagen fibers in atherosclerotic lesions by ImageJ software. Int J Clin Experiment Med. 2017;10(10):14904-10.

Katerji M, Filippova M, Duerksen-Hughes P. Approaches and methods to measure oxidative stress in clinical samples: research applications in the cancer field. Oxidat Med Cell Long. 2019;2019:1279250.

Schäfer M, Werner S. Oxidative stress in normal and impaired wound repair. Pharmacolog Res. 2008;58(2):165-71.

Dunnill C, Patton T, Brennan J, Barrett J, Dryden M, Cooke J, et al. Reactive oxygen species (ROS) and wound healing: the functional role of ROS and emerging ROS-modulating technologies for augmentation of the healing process. Int Wound J. 2017;14(1):89-96.

Zhang W, Chen L, Xiong Y, Panayi AC, Abududilibaier A, Hu Y, et al. Antioxidant therapy and antioxidant-related bionanomaterials in diabetic wound healing. Front Bioeng Biotechnol. 2021;9:707479.

Reilly DM, Lozano J. Skin collagen through the lifestages: importance for skin health and beauty. Plast Aesthet Res. 2021;8:2.

Rattan R, Nayak D. High levels of plasma malondialdehyde, protein carbonyl, and fibrinogen have prognostic potential to predict poor outcomes in patients with diabetic foot wounds: a preliminary communication. Int J Low Extrem Wounds. 2008;7(4):198-203.

González R, Fernández-Sánchez ML, Fernández JC, Menéndez FV, Sanz-Medel A. Selenium levels and glutathione peroxidase activity in the plasma of patients with type II diabetes mellitus. J Trace Element Med Biol. 2016;37:44-9.

Thomas S, Vieira CS, Hass MA, Lopes LB. Stability, cutaneous delivery, and antioxidant potential of a lipoic acid and α-tocopherol codrug incorporated in microemulsions. J Pharmaceut Sci. 2014;103(8):2530-8.

Li RK, Cowan DB, Mickle DA, Weisel RD, Burton GW. Effect of vitamin E on human glutathione peroxidase (GSH-PX1) expression in cardiomyocytes. Free Radic Biol Med. 1996;21(4):419-26.

Bryan J. Moist wound healing: a concept that changed our practice. J Wound Care. 2004;13(6):227-8.

Hoff J, Karl B, Gerstmeier J. Controlled release of the α-tocopherol-derived metabolite α-13'-carboxychromanol from bacterial nanocellulose wound cover improves wound healing. Nanomaterials (Basel, Switzerland). 2021;11(8):1939.

Qian B, Li J, Guo K. Antioxidant biocompatible composite collagen dressing for diabetic wound healing in rat model. Regenerat Biomat. 2021;8(2):003.