Melatonin attenuates <sup>60</sup>Co γ‐ray‐induced hematopoietic, immunological and gastrointestinal injuries in C57BL/6 male mice

Khan, Shahanshah; Adhikari, Jawahar Singh; Rizvi, Abbas; Chaudhury, N. K.

doi:10.1002/tox.22254

Cited by 22 publications

(29 citation statements)

References 73 publications

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“…Therefore, its use as a prophylactic agent could reduce morbidity and limit radiation-induced injury in cancer patients under radiotherapy [86,102].…”

Section: B) Melatonin As a Radio-protective Agentmentioning

confidence: 99%

“…Other authors have reported that it prevents hemolysis in irradiated human red blood cells [85]. Pretreatment with melatonin guards erythrocytes, granulocytes, macrophages, megakaryotes and T cells against radiation-induced cellular injury and also inhibits splenocyte apoptosis in whole-body irradiated mice [86]. It also prevents radiation-induced damage in retinal cells [87], thymocytes [88] and bone-marrow cells in mice [89].…”

Section: B) Melatonin As a Radio-protective Agentmentioning

confidence: 99%

“…Its administration prior to irradiation guards against intestinal damage caused by X-rays [100]. It prevents mucosal intestinal damage caused by radiotherapy by countering structural changes in the small intestine (as evidenced by the villous pattern of the intestinal mucosa) [101] and also inhibits gut bacterial translocation to the spleen, liver and kidney [86].…”

Section: B) Melatonin As a Radio-protective Agentmentioning

confidence: 99%

“…The mechanisms involved in melatonin as a radioprotective agent have been attributed to its antioxidant properties, which reduce radiation-induced DNA damage and lipid peroxidation, and to its protection of the immune system by reducing apoptosis through the inhibition of p53 and Bax and by enhancing anti-apoptotic protein Bcl-2 [86,93,102]; it is also involved in repairing lesions in cellular DNA [103].…”

Section: B) Melatonin As a Radio-protective Agentmentioning

confidence: 99%

“…Furthermore, it can prevent the loss of proliferative progenitor stem cells caused by radiation and enhance their capacity to repopulate the tissue. In addition, ionizing radiation exposure causes oxidative damage to DNA, which arrests the cell cycle, inhibits growth and increases cell death [86]. Thus, protection of cellular DNA is of the utmost importance in reducing radiation-induced cellular perturbation and also in the proliferation/differentiation of normal cells.…”

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confidence: 99%

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Oral Mucositis: Melatonin Gel an Effective New Treatment

Moneim¹,

Guerra‐Librero²,

Florido³

et al. 2017

Preprint

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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...

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“…Therefore, its use as a prophylactic agent could reduce morbidity and limit radiation-induced injury in cancer patients under radiotherapy [86,102].…”

Section: B) Melatonin As a Radio-protective Agentmentioning

confidence: 99%

Section: B) Melatonin As a Radio-protective Agentmentioning

confidence: 99%

Section: B) Melatonin As a Radio-protective Agentmentioning

confidence: 99%

Section: B) Melatonin As a Radio-protective Agentmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Oral Mucositis: Melatonin Gel an Effective New Treatment

Moneim¹,

Guerra‐Librero²,

Florido³

et al. 2017

Preprint

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Melatonin promotes neuroblastoma cell differentiation by activating hyaluronan synthase 3‐induced mitophagy

et al. 2019

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Neuroblastoma is the second most common pediatric malignancy and has a high rate of spontaneous remission. Uncovering the mechanisms underlying neuroblastoma cell differentiation is critical for therapeutic purposes. A neuroblastoma cell line (N2a) treated with either serum withdrawal (<2.5%) or melatonin (>0.1 nmol/L) for 24 hours was used as a cell differentiation research model. Interestingly, the hyaluronan synthase 3 (HAS3) protein was induced in differentiated N2a cells. N2a‐allografted nude mice received an intraperitoneal injection of melatonin (40 or 80 mg/kg/day for 3 weeks). The mean tumor volume in mice treated with 80 mg/kg melatonin was smaller than that in PBS‐treated mice (1416.3 and 3041.3 mm 3 , respectively, difference = 1625 mm 3 , * P = 0.0003, n = 7 per group). Compared with the vector control group, N2a cells with forced HAS3 overexpression showed significantly increased neuron length (* P = 0.00082) and neurite outgrowth (* P = 0.00059). Intracellular changes in autophagy, including distorted mitochondria with abnormal circular inner membranes, were detected by transmission electron microscopy (TEM). Our study demonstrated that HAS3‐mediated signaling activated by physiological concentrations of melatonin (>0.1 nmol/L) triggered significant N2a cell differentiation. These results provide molecular data with potential clinical relevance for therapeutic drug development.

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Melatonin as an adjuvant in radiotherapy for radioprotection and radiosensitization

et al. 2018

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It is estimated that more than half of cancer patients undergo radiotherapy during the course of their treatment. Despite its beneficial therapeutic effects on tumor cells, exposure to high doses of ionizing radiation (IR) is associated with several side effects. Although improvements in radiotherapy techniques and instruments could reduce these side effects, there are still important concerns for cancer patients. For several years, scientists have been trying to modulate tumor and normal tissue responses to IR, leading to an increase in therapeutic ratio. So far, several types of radioprotectors and radiosensitizers have been investigated in experimental studies. However, high toxicity of chemical sensitizers or possible tumor protection by radioprotectors creates a doubt for their clinical applications. On the other hand, the protective effects of these radioprotectors or sensitizer effects of radiosensitizers may limit some type of cancers. Hence, the development of some radioprotectors without any protective effect on tumor cells or low toxic radiosensitizers can help improve therapeutic ratio with less side effects. Melatonin as a natural body hormone is a potent antioxidant and anti-inflammatory agent that shows some anti-cancer properties. It is able to neutralize different types of free radicals produced by IR or pro-oxidant enzymes which are activated following exposure to IR and plays a key role in the protection of normal tissues. In addition, melatonin has shown the ability to inhibit long-term changes in inflammatory responses at different levels, thereby ameliorating late side effects of radiotherapy. Fortunately, in contrast to classic antioxidants, some in vitro studies have revealed that melatonin has a potent anti-tumor activity when used alongside irradiation. However, the mechanisms of its radiosensitive effect remain to be elucidated. Studies suggested that the activation of pro-apoptosis gene, such as p53, changes in the metabolism of tumor cells, suppression of DNA repair responses as well as changes in biosynthesis of estrogen in breast cancer cells are involved in this process. In this review, we describe the molecular mechanisms for radioprotection and radiosensitizer effects of melatonin. Furthermore, some other proposed mechanisms that may be involved are presented.

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Melatonin attenuates ⁶⁰Co γ‐ray‐induced hematopoietic, immunological and gastrointestinal injuries in C57BL/6 male mice

Cited by 22 publications

References 73 publications

Oral Mucositis: Melatonin Gel an Effective New Treatment

Oral Mucositis: Melatonin Gel an Effective New Treatment

Melatonin promotes neuroblastoma cell differentiation by activating hyaluronan synthase 3‐induced mitophagy

Melatonin as an adjuvant in radiotherapy for radioprotection and radiosensitization

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Melatonin attenuates 60Co γ‐ray‐induced hematopoietic, immunological and gastrointestinal injuries in C57BL/6 male mice

Cited by 22 publications

References 73 publications

Oral Mucositis: Melatonin Gel an Effective New Treatment

Oral Mucositis: Melatonin Gel an Effective New Treatment

Melatonin promotes neuroblastoma cell differentiation by activating hyaluronan synthase 3‐induced mitophagy

Melatonin as an adjuvant in radiotherapy for radioprotection and radiosensitization

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Melatonin attenuates ⁶⁰Co γ‐ray‐induced hematopoietic, immunological and gastrointestinal injuries in C57BL/6 male mice