Nitric oxide-based treatments improve wound healing associated with diabetes mellitus

Bahadoran, Zahra1; Mirmiran, Parvin2; Hosseinpanah, Farhad3; Kashfi, Khosrow4,*; Ghasemi, Asghar5,

Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran²Department of Clinical Nutrition and Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran³Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran⁴Department of Molecular, Cellular, and Biomedical Sciences, Sophie Davis School of Biomedical Education, City University of New York School of Medicine, New York, NY, USA⁵Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Funding:This work was supported by Shahid Beheshti University of Medical Sciences, Tehran, Iran (No. 43009719).

Abstract

Non-healing wounds are long-term complications of diabetes mellitus (DM) that increase mortality risk and amputation-related disability and decrease the quality of life. Nitric oxide (NO·)-based treatments (i.e., use of both systemic and topical NO· donors, NO· precursors, and NO· inducers) have received more attention as complementary approaches in treatments of DM wounds. Here, we aimed to highlight the potential benefits of NO·-based treatments on DM wounds through a literature review of experimental and clinical evidence. Various topical NO·-based treatments have been used. In rodents, topical NO·-based therapy facilitates wound healing, manifested as an increased healing rate and a decreased half-closure time. The wound healing effect of NO·-based treatments is attributed to increasing local blood flow, angiogenesis induction, collagen synthesis and deposition, re-epithelization, anti-inflammatory and anti-oxidative properties, and potent broad-spectrum antibacterial effects. The existing literature lacks human clinical evidence on the safety and efficacy of NO·-based treatments for DM wounds. Translating experimental favors of NO·-based treatments of DM wounds into human clinical practice needs conducting clinical trials with well-predefined effect sizes, i.e., wound reduction area, rate of wound healing, and hospital length of stay.

摘要：伤口不愈合是糖尿病长期并发症之一，会增加患者死亡率和截肢，并降低其生活质量。基于一氧化氮的治疗，如全身和局部使用一氧化氮供体、一氧化氮前体和一氧化氮诱导剂等，可作为糖尿病伤口治疗的替代疗法，并受到广泛的关注。此次综述通过总结实验和临床证据，分析一氧化氮疗法对糖尿病伤口愈合的潜在益处。目前已使用多种基于一氧化氮的局部疗法。在啮齿类动物中，一氧化氮局部治疗有助于伤口愈合，增加愈合率，缩短半闭合时间。一氧化氮促进伤口愈合的效果主要在于增加局部血流量，促进血管生成、胶原合成/沉积和再上皮化、抗炎、抗氧化以及广谱抗菌作用。现有文献尚缺乏一氧化氮治疗糖尿病伤口的安全性和有效性的临床证据。将一氧化氮治疗糖尿病伤口的实验优势转化为临床实践还需要结局指标为伤口缩小面积、伤口愈合率和住院时间的临床试验证据。