Camel whey protein enhances diabetic wound healing in a streptozotocin-induced diabetic mouse model: the critical role of β-Defensin-1, -2 and -3

Gamal Badr

doi:10.1186/1476-511x-12-46

Abstract

BackgroundDelayed wound healing is considered one of the most serious diabetes-associated complications. The presence of replicating organisms such as bacteria within a diabetic’s wound is considered one of the most important factors that impair cutaneous wound healing and the potential cellular and/or molecular mechanisms that are involved in the healing process. Defensins, which are anti-microbial peptides, have potent bactericidal activity against a wide spectrum of the bacterial and fungal organisms that are commonly responsible for wound infections. We recently demonstrated that camel whey proteins (WPs) expedite the healing of diabetic wounds by enhancing the immune response of wounded tissue cells and by alleviating some of the diabetic complications.MethodsIn the present study, we investigated the effects of WP supplementation on the mRNA and protein expression levels of β-defensin-1 (BD-1), 2 and 3 and subsequently on the wound healing process in a streptozotocin (STZ)-induced diabetic mouse model. In this study, three groups of mice were used (10 mice per group): group 1, the non-diabetic mice (control); group 2, the diabetic mice; and group 3, the diabetic mice that received a daily supplement of undenatured WP (100 mg/kg of body weight) via oral gavage for 1 month.ResultsCompared with the non-diabetic control mice, the diabetic mice exhibited delayed wound closure that was characterized by a reduction in hydroxyproline content (indicator of collagen deposition), a marked elevation in free radical levels and a prolonged elevation in the levels of inflammatory cytokines, including interleukin-6 (IL-6), transforming growth factor-beta (TGF-β) and tumor necrosis factor-alpha (TNF-α). Interestingly, compared with the diabetic mice that did not receive WP supplementation, the diabetic mice with WP had an accelerated closure and healing process of their wounds. The WP supplementation also decreased their levels of free radicals and restored their hydroxyproline content; proinflammatory cytokine levels; and expression of BD-1, 2 and 3 in the wounded tissue.ConclusionWP supplementation may be beneficial for improving the healing and closure of diabetic wounds.

Highlights

Delayed wound healing is considered one of the most serious diabetes-associated complications
Supplementation with camel Whey protein (WP) improved wound closure in diabetic mice We first evaluated the macroscopic changes in the skin excisional wound sites of the control mice, diabetic mice and diabetic mice supplemented with WP
We observed that the wound sites of the mice in all of the experimental groups exhibited similar morphology on day 1 post injury, whereas the wounds of the control and WP-supplemented diabetic groups were almost closed by day 13 post injury

Summary

Introduction

Delayed wound healing is considered one of the most serious diabetes-associated complications. ROS plays crucial roles in cell signaling and in the immune response, higher levels of ROS cause oxidative stress during wound healing. Regulating oxidative stress and the inflammatory response is an important factor in cutaneous wound healing. Proinflammatory cytokines, including interleukins 1α and 1β (IL-1α and IL-1β), IL-6 and tumor necrosis factor alpha (TNF-α), play important roles in wound repair, such as the stimulation of keratinocyte and fibroblast proliferation, synthesis and breakdown of extracellular matrix proteins, fibroblast chemotaxis and regulation of the immune response [8]. Previous studies have demonstrated that transforming growth factor-β (TGF-β) plays critical roles in wound repair This cytokine functions in leukocyte chemotaxis, fibroblast and smooth muscle cell mitogenesis and extracellular matrix deposition during granulation tissue formation [8,10]. In a recently published study, burn wounds exhibited a moderately lower expression of BD-1 than healthy tissues [14]

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