Impaired wound healing, a common complication of diabetes mellitus, is characterized by diminished collagen production and impaired angiogenesis . These complications are caused by the action of released free radicals , which damage multiple cellular components, such as lipids, proteins and DNA. Furthermore, multiple factors in the diabetic wound, including increased apoptosis, decreased vascular recovery, an aberrant inflammatory response and delayed cellular turnover, contribute to impaired wound healing . Additionally, the production of reactive oxygen species (ROS) by inflammatory cells and other cell types in the wound is required for defense against invading bacteria. Moreover, at physiological levels, ROS are also important regulators of various intracellular signaling pathways . Oxidative stress is an important pathogenic factor in diabetic wound complications and affects cell replication and life span. Intracellular glutathione (GSH) can normalize skin cell functions that are disrupted by in vitro cell growth under hyperglycemic conditions . Although ROS plays crucial roles in cell signaling and in the immune response, higher levels of ROS cause oxidative stress during wound healing. Therefore, regulating oxidative stress and the inflammatory response is an important factor in cutaneous wound healing. Wound healing can be defined as a complex, multi-stage process that involves distinct phases: inflammation, the formation of granulation tissue, the production of new structures and tissue remodeling . Moreover, many factors can interfere with one or more phases of this process and thus may affect wound healing by causing improper or impaired tissue repair. Collagen is the predominant extracellular protein in the granulation tissue of a healing wound. In addition, the synthesis of collagen rapidly increases in the wound area soon after an injury, and this increase in collagen provides strength and integrity to the tissue matrix. The measurement of hydroxyproline, which is produced by the breakdown of collagen, has been used as an index of collagen turnover . The cytokines and chemokines secreted by skin-resident cells (keratinocytes, fibroblasts and endothelial cells) and by inflammatory cells are involved in 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 . In addition, recent reports have indicated that the dysregulation of TNF-α impairs the healing of diabetic wounds and that this dysregulation may involve enhanced apoptosis and decreased proliferation of fibroblasts . 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]. One common denominator associated with the regulation of wound healing events is human β-defensin 2 (BD-2). Skin wounding induces cutaneous BD-2 expression, and diabetic wounds have been associated with inadequate human β-defensin expression . Human BD-2 may also participate in other aspects of innate immunity because it chemoattracts monocytes and immature dendritic cells . In burned skin, human β-defensin 1 (BD-1) is expressed by the dermal glands, including hair shafts. Moreover, human BD-2 and 3 have been found in the remaining keratin layers and glands of the lower dermis . In a recently published study, burn wounds exhibited a moderately lower expression of BD-1 than healthy tissues .
The improvement in immune function using dietary antioxidants can play an important role in the prevention of many human diseases and diabetic complications. Camel whey proteins (WPs) include a heterogeneous group of proteins, including serum albumin, α-lactalbumin, immunoglobulin, lactophorin and peptidoglycan recognition protein . Dietary whey supplementations may improve wound healing by increasing GSH synthesis and cellular antioxidant defense . Therefore, WPs may be a therapeutic tool for the treatment of oxidative stress-associated diseases . The oral administration of an undenatured WP increases the GSH levels of severa GSH-deficient patients, including those with advanced human immunodeficiency virus (HIV) infection . Recent studies have indicated that whey increases the antioxidant activity in the body, combats fatigue and inflammation, hastens healing, improves stamina and may discourage related infections due to the immune system-enhancing and natural antibiotic properties of its components [19, 20]. Nevertheless, few studies have investigated the influence of WPs on wound healing. The aim of this study was to investigate the effects of WP supplementation on the mRNA and protein expression levels of BD-1, 2 and 3 and subsequently to observe the effects of WP on the wound healing process in a streptozotocin (STZ)-induced diabetic mouse model.