The effects of topical melatonin on oxidative stress, apoptosis signals,and p53 protein expression during cutaneous wound healing

Abstract

IntroductionWound healing is a complex and well-designed repair process that occurs after any injury, such as surgical procedures or trauma. The process is divided into three serial phases: inflammation, tissue formation, and tissue remodeling (Wu and Chen, 2014). Apoptosis is important to the wound healing process, especially in removing inflammatory cells and inhibiting scar formation. The early phase of inflammation is characterized by the invasion of neutrophils, macrophages, and lymphocytes to the wound area. The fibroblasts then migrate and synthesize extracellular matrix components. Inflammatory cells must be removed in order to begin this next phase of wound healing. Remodeling of granulation tissue during the wound healing process is also accompanied by the apoptosis of fibroblasts (Rai et al., 2005;Wu and Chen, 2014). Dysregulation in these apoptotic processes may result in abnormal wound healing, such as hypertrophic scars and keloid formation (Greenhalgh, 1998), or may delay wound healing (Deveci et al., 2005;Blakytny and Jude, 2006). p53 is generally known as a tumor suppressor and can induce apoptosis via transcription-dependent or -independent mechanisms (Lippens et al., 2009). Reactive oxygen species (ROS) that arise after cutaneous injury may worsen the healing process and induce apoptosis (Hameedaldeen et al., 2014). Low and normal levels of ROS play important roles in wound repair and signal transduction for reepithelialization and proliferation of cells, such as the collagenase activity and the epidermal growth factor signaling. However, higher levels of ROS can cause oxidative stress and may damage intracellular macromolecules such as DNA, lipids, and proteins. Therefore, regulating oxidative stress and the inflammatory response is important during the cutaneous wound healing process (Schäfer and Werner, 2008;Hameedaldeen et al., 2014). The utilization of antioxidants has been considered as an effective therapeutic approach in wound healing (James et al., 2001;Sharifi et al., 2012). Melatonin (N-acetyl-5-methoxytryptamine) is a hormone produced primarily by the pineal gland and secreted in the dark during night. It modulates sleep, reproduction, circadian rhythm, and immunity. Additionally, melatonin is a potent antioxidant and directly detoxifies oxygen and nitrogen-based reactants Sener et al., 2009). It affects the activity and the levels of cellular mRNA of antioxidant enzymes including Abstract: Elimination of reactive oxygen species (ROS) can be an important strategy to improve healing of wounds. ROS have an effect on proliferation and cell survival signaling, which results in alteration of apoptotic pathways in cells. Melatonin has antioxidant properties on skin wounds. In our study, we investigated the effects of topical melatonin (3%, w/w) on apoptosis and p53 protein expression together with parameters of oxidative stress in a cutaneous excision wound model. Bcl-2 protein levels in wound tissue at the end of days 3, 7, and 14 were significantly increased, while caspase-3 activity an...

Topical metformin accelerates wound healing by promoting collagen synthesis and inhibiting apoptosis in a diabetic wound model

“…In a study evaluating the effect of apoptosis on wound healing in a diabetic condition, Desta et al showed that impaired gingival wound healing is common in diabetic mice due to increased fibroblast apoptosis 37 . In another wound model in which melatonin was applied topically, it was reported that the amounts of caspase‐3 and p53 decreased significantly in the treatment groups, but these effects did not accelerate wound healing 38 . A cutaneous wound model study in mice showed that transient inhibition of p53 with pifithrin‐α (PFT‐α) promotes early cell proliferation, which is essential for rapid tissue repair 39 .…”

Effect of Horse-chestnut seed extract on matrix metalloproteinase-1 and -9 during diabetic wound healing

“…MPO is the most abundant proinflammatory enzyme stored in the azurophilic granules of neutrophilic granulocytes (Cheng, Kuang, & Ju, ). MPO activity is frequently measured to assess the accumulation of PMN tissue in inflammatory tissues (Sener et al, ). Inflammation and neutrophil infiltration were associated with impaired wound healing in diabetic patients.…”

“…Activated polymorphonuclear leukocytes (PMNs) release myeloperoxidase (MPO). To determine accumulation of tissue PMNs in inflamed tissues, MPO activity is frequently measured (Sener et al, ). The skin MPO levels were determined using a procedure similar to that of Hillegas et al ().…”

“…The paper was then scanned and the wound size was analyzed using ImageJ software. The percentage of wound closure was calculated according to the following formula (Sener et al, ): % of wound closure = (initial (day 0) wound size—specific day wound size)/initial wound size) × 100.…”

The Effect of algan hemostatic agent (AHA) on wound healing

“…Then, wound shapes were transferred on a 1 mm chart paper. The contraction percentage of wound area was calculated by using the following formula (16). The contraction percentage of wound area = (initial wound sizespecific day wound size)/initial wound size) × 100.…”