Effect of melatonin on wound healing in normal and pinealectomized rats

Bülbüller, Nurullah; Doğru, Osman; Yekeler, Hayrettin; Çetinkaya, Ziya; İlhan, Nevin; Kırkıl, Cüneyt

doi:10.1016/j.jss.2004.05.022

Cited by 25 publications

(21 citation statements)

References 20 publications

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“…Pinealectomy, which decreases melatonin level in the blood, has been found to reduce the surface area of the wound and accelerate wound repair (Drobnik and Dabrowski, 1996). Bulbuller et al (2005) observed that subcutaneous melatonin application decreased collagen synthesis and epithelium proliferation and indicated undesirable effects on incision and anastomotic wound healing in normal and pinealectomized rats. However, positive improvement in the wound healing process has been detected due to topically and systematically administered melatonin on chronic wound healing in rats with pinealectomy (Ozler et al, 2010) and also on pressure ulcer in rats (Sener et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

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

Şener¹,

Çevik²,

Doğan³

et al. 2015

Turk J Biol

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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...

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Section: Discussionmentioning

confidence: 99%

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

Şener¹,

Çevik²,

Doğan³

et al. 2015

Turk J Biol

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“…The suggested dose required to exert antioxidant properties was considered 10mg/kg BW, in animal experiments (40) . However Bulbuller et al observed that subcutaneous melatonin application decreased collagen synthesis and epithelium proliferation and indicated undesirable effects on incision and anastomotic wound healing in normal and pinealectomized rats (41) .…”

Section: Discussion:-mentioning

confidence: 99%

Biological Impact of Melatonin on the Healing of Albino Rats’ Tongue Ulcer.

Amin.¹,

Adel²

2017

IJAR

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“…BP is considered to be the most important factor in assessing the quality of the intestinal suture line [25] , so that the protective effect of melatonin on wound healing of colonic anastomosis in the presence of bacterial peritonitis is supported by the BP results. In our study, the lowest mean BP result belongs to group B.…”

Section: Discussionmentioning

confidence: 99%

Effect of Melatonin on Healing of Colonic Anastomosis in a Rat Model of Peritonitis

Özen¹,

Ekíngen²,

Taşlıpınar

et al. 2006

Eur Surg Res

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Background: The aim of this study is to determine the effect of melatonin on intestinal anastomosis in the presence of peritonitis. Material and Methods: 32 Wistar albino rats were randomized into four groups (n = 8): A (sham), B (control), C (melatonin 5 mg/kg), and D (melatonin 10 mg/kg). In group A, only cecal dissection was carried out. In the other groups, cecal ligation and puncture (CLP) followed cecal dissection in order to induce bacterial peritonitis. 24 h after the previous operation, cecal resection and iliocolic anastomosis were performed in the rats of all groups. In group C (5 mg/kg) and group D (10 mg/kg), melatonin was injected for 5 consecutive days starting after CLP. At the 48th hour of the CLP procedure, blood was drawn via the tail vein for tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) analysis, and on the 4th day of the experiment relaparotomy was carried out for bursting pressure (BP) measurements. The intestinal tissue containing the anastomotic line was then snap-frozen in liquid nitrogen and stored at –80°C for determination of tissue levels of malondialdehyde (MDA) and glutathione (GSH). Results: The tissue MDA level, blood TNF-α and IL-6 levels of group B were significantly higher than in the other groups, whereas the BP results and GSH levels of group B were found to be significantly lower than in the other groups. The results of groups C and D are statistically different from those of group B. When we compared the results of groups C and D, we found significantly higher results in terms of BP and GSH levels in group D and also significantly lower results in terms of MDA, blood TNF-α and IL-6 levels in group D. Conclusion: The findings of this experiment suggest that melatonin has a dose-independent positive effect on wound healing of colonic anastomosis.

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Effect of melatonin on wound healing in normal and pinealectomized rats

Cited by 25 publications

References 20 publications

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

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

Biological Impact of Melatonin on the Healing of Albino Rats’ Tongue Ulcer.

Effect of Melatonin on Healing of Colonic Anastomosis in a Rat Model of Peritonitis

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