Oral Mucositis: Melatonin Gel an Effective New Treatment

Abstract

Abstract:The current treatment for cervico-facial cancer involves radio and/or chemotherapy.Unfortunately, cancer therapies can lead to local and systemic complications such as mucositis, which is the most common dose-dependent complication in the oral cavity and gastrointestinal tract.Mucositis can cause a considerably reduced quality of life in cancer patients already suffering from physical and psychological exhaustion. However, melatonin, whose role in the treatment of mucositis has recently been investigated, offers an effective alternative therapy in the prevention and/or management of radio and/or chemotherapy-induced mucositis. This review focuses on the pathobiology and management of mucositis in order to improve the quality of cancer patients' lives.Keywords: mucositis; radiotherapy; chemotherapy; pathophysiology; management; melatonin Overview of mucositis pathobiologyMucositis, one of the most severe toxic side effects of cancer therapy, can affect the entire gastrointestinal tract, with the oral cavity being the most common affected site. It presents in virtually all head and neck cancer patients receiving chemo and/or radiotherapy, in 60-85% of those receiving myeloablative therapy for stem-cell transplantation and in 20-40% of patients receiving conventional chemotherapy [1][2][3]. The use of concomitant chemotherapy and/or targeted agents increases the risk of mucositis.Oral lesions lead to considerably decreased quality of life in these patients due to solid and liquid food dysphagia, dysarthria and odynophagia, resulting in depression in some patients, who often require percutaneous endoscopic gastrostomy tube insertion [4]. In addition, mucositis lesions may represent a gateway to opportunistic infections, can complicate cancer treatment and extend hospitalization [5][6]. On the other hand, given its dose-limiting toxicity for both chemo and radiotherapy, mucositis can have a direct impact on survival rates [7]. Pathophysiology of mucositisRecent developments in mucositis research have highlighted multiple factors which contribute to mucosal injury [8]. A five-phase chronological process has been proposed: initiation, primary damage response (upregulation and message generation), signal amplification, ulceration and the healing phase [9]. Mucositis commences when gastrointestinal (GI) mucosa are exposed to cytotoxic agents, resulting in cellular DNA damage and cell death, mainly through the generation of oxidative Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 9 March 2017 doi:10.20944/preprints201703.0052.v1Peer-reviewed version available at Int. J. Mol. Sci. 2017, 18, , 1003 doi:10.3390 The progression of mucositis is characterized by significant inflammatory mediator up-regulation due to the activation of the NF-κB pathway (upregulation and message generation phase). This is followed by the signaling and amplification phase, during which, once activated by chemotherapy and ROS, NF-κB promotes the expression of multiple pro-inflammatory molecules, including inducible nitric oxid...

Combination of melatonin and rapamycin for head and neck cancer therapy: Suppression of AKT/mTOR pathway activation, and activation of mitophagy and apoptosis via mitochondrial function regulation

“…Melatonin reportedly protects various organs from chemotherapy‐ and radiotherapy‐induced toxicity . Thus, the combination of melatonin with rapamycin may both achieve an enhanced oncostatic effect and overcome a major limitation of anticancer treatment.…”

“…Melatonin (N‐acetyl‐5‐methoxytryptamine) is a potent free radical scavenger with anti‐oxidant and anti‐inflammatory properties, which has well‐known functions in immune system regulation, modulation of mitochondrial activity, and regulation of cell death and autophagy . Moreover, melatonin has attracted attention as a natural oncostatic agent that can suppress neoplastic growth in a variety of tumours .…”

Diabetic Status Influences the Storage of Melatonin in Human Salivary Glands

“…This assumption has recently been questioned, since several organs and glands were claimed to produce melatonin (Hevia et al, ; Venegas et al, ; Acuña‐Castroviejo et al, ) and mitochondria are believed to be the preferentially sites of melatonin production in peripheral tissues (Tan D‐X et al, , Reiter et al, ; Suofu et al, ). Moreover, the oral mucosa and the salivary glands themselves have been considered extrapineal sources of this indoleamine, because the enzymes involved in melatonin synthesis were found in both the oral mucosa and the glandular parenchyma (Shimozuma et al, ; Abdel Moneim et al, ). Moreover, besides passive diffusion, new evidence supports the existence of an as yet not fully defined mechanism that may regulate the diffusion and storage of melatonin inside the cells (Venegas et al, ; Hevia et al, ).…”

Efficacy of Melatonin in prevention of radiation‐induced oral mucositis: A randomized clinical trial

“…Many studies in the literature reported the use of melatonin in the treatment of different human oral conditions due to its oncostatic and cytoprotective properties (Mihandoost, Shirazi, Mahdavi, & Aliasgharzadeh, ; Wang et al, ). Both animals (Abdel Moneim et al, ; Meltz, Reiter, Herman, & Kumar, ) and human (Reiter, Herman, & Meltz, ; ) studies have shown melatonin to be protective against radiation‐induced cellular damage. In 2017, Abdel Moneim et al () demonstrated that melatonin gel shields rats from postradiation oral mucositis.…”

“…Both animals (Abdel Moneim et al, ; Meltz, Reiter, Herman, & Kumar, ) and human (Reiter, Herman, & Meltz, ; ) studies have shown melatonin to be protective against radiation‐induced cellular damage. In 2017, Abdel Moneim et al () demonstrated that melatonin gel shields rats from postradiation oral mucositis.…”