Abstract
Impaired wound healing is a major clinical problem in patients with diabetes and is the leading cause of lower limb amputation. This study is aimed to observe the effects of small molecule oligopeptides isolated from sea cucumber (SCCOPs) on the wound healing process in diabetic mice. Ninety db/db male mice were divided into five groups, including the model control group, whey protein group (0.50 g/kg) and three SCCOPs dose groups (0.25 g/kg, 0.50 g/kg and 1.00 g/kg). Additionally, 18 db/m male mice were used as normal control group. After full-thickness incisions on the dorsum, mice in SCCOPs-treated groups were intragastrically administered SCCOPs, while others were administered vehicle or whey protein. Mice were sacrificed on days 4, 7 and 14. The wound healing condition, inflammatory response, angiogenesis, collagen deposition, oxidative stress and nutritional status were evaluated. A pathological report showed increased vascularisation, collagen deposition and epithelialisation in SCCOPs-treated groups. SCCOPs-treated mice showed decreased C-reactive protein (CRP), interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, chemokine (C-C motif) ligand 2 (CCL2) and reactive oxygen species (ROS) contents, and increased IL-10, stromal cell-derived factor-1 alpha (SDF-1α), nitric oxide (NO), albumin (ALB), prealbumin (PA) and transferrin (TRF) levels and vascular endothelial growth factor (VEGF) expression. All parameters were significant (p < 0.05) in comparison to model control group. These results suggest that treatment with SCCOPs can promote significant wound healing in diabetic mice.
Highlights
Diabetes is a public health problem worldwide
Blood glucose levels in diabetic mice used in the present study were consistently higher than 300 mg/dL and the levels were not changed by administration of SCCOPs
The results showed that no significant differences on body weight and levels of ALB, PA and TRF were observed among whey protein group (WP) and SCCOPs-treated groups on days 4, 7 and 14, indicating that SCCOPs’ ability to improve diabetic wound healing may not be attributed to dietary protein intake
Summary
Diabetes is a public health problem worldwide. Studies showed that the number of diabetics in the world was 415 million in 2015, and it may reach 642 million by 2040 [1]. The complications caused by diabetes are the main cause of disability and death in diabetic patients, among which impaired wound healing is a major clinical problem and is the leading cause of lower extremity amputation [2,3,4]. Care for diabetic wounds remains a significant clinical problem and the development of therapies to improve wound healing in diabetic patients is of critical importance. Pharmacologic therapies tried to address this issue through either the application of labgrown dermal substitutes, stem cell therapies, or the delivery of super-physiological concentrations of recombinant growth factors [5]. These have proven to be difficult to maintain, and have led in some cases to serious undesired side effects [6]. Compounds that provide greater symptomatic relief with less overall toxicity and minimal risks are preferred
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