RESUMEN
Melatonin exerts various physiological effects through melatonin receptors and their ability to scavenge free radicals. Radiotherapy is a common treatment for head and neck tumors, but stomatitis, a side effect affecting irradiated oral mucosa, can impact treatment outcomes. This study investigated the preventive effect of melatonin, a potent free radical scavenger, on radiation-induced oral mucositis. Mice were irradiated with 15 Gy of X-ray radiation to the head and neck, and the oral mucosa was histologically compared between a melatonin-administered group and a control group. The results showed that radiation-induced oral mucositis was suppressed in mice administered melatonin before and after irradiation. It was suggested that the mechanism involved the inhibition of apoptosis and the inhibition of DNA damage. From these findings, we confirmed that melatonin has a protective effect against radiation-induced oral mucositis.
Asunto(s)
Melatonina , Estomatitis , Animales , Ratones , Melatonina/farmacología , Melatonina/uso terapéutico , Estomatitis/tratamiento farmacológico , Estomatitis/etiología , Estomatitis/prevención & control , Mucosa Bucal , Cabeza , ApoptosisRESUMEN
Melatonin, discovered in 1958, is secreted by the pineal gland primarily during the night. Its secretion is controlled by the light/dark cycle of the environment. Melatonin is also produced in and secreted by various extrapineal organs, tissues and cells and its synthesizing enzyme arylalkylamine N-acetyltransferase (AANAT) is expressed in various extrapineal organs, tissues and cells. Recently, it was reported that melatonin is present in saliva, but it is not certain where melatonin was synthesized and whether it was secreted into saliva and what function it may have in saliva. The present study was performed to investigate where melatonin was synthesized and whether it was secreted by salivary glands into saliva. We performed immunohistochemical analysis of the expression of AANAT in rat parotid, submandibular and sublingual glands and the expression of both AANAT and hydroxyindole-O-methyltransferase (HIOMT) in human submandibular glands. We evaluated the expression of AANAT and HIOMT mRNA in rat submandibular glands by quantitative reverse transcription-polymerase chain reaction. As a result, we observed expression of AANAT in epithelial cells of striated ducts in rat salivary glands and expression of AANAT, HIOMT and melatonin in epithelial cells of striated ducts in human submandibular glands. In addition, we also confirmed the expression of the most potent melatonin receptor, melatonin 1a receptor, in rat buccal mucosa. Our findings suggest that melatonin might be produced and secreted by salivary glands directly into saliva and that it might play some physiological role in the oral cavity.
Asunto(s)
Acetilserotonina O-Metiltransferasa/metabolismo , N-Acetiltransferasa de Arilalquilamina/metabolismo , Melatonina/biosíntesis , Glándulas Salivales/enzimología , Acetilserotonina O-Metiltransferasa/análisis , Acetilserotonina O-Metiltransferasa/genética , Animales , N-Acetiltransferasa de Arilalquilamina/análisis , N-Acetiltransferasa de Arilalquilamina/genética , Humanos , Inmunohistoquímica , Masculino , Mucosa Bucal/citología , ARN Mensajero/análisis , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Glándulas Salivales/citologíaRESUMEN
Leptin, a 16 kDa non-glycolated polypeptide of 146 amino acids produced by the ob gene, has a variety of physiological roles not only in lipid metabolism, hematopoiesis, thermogenesis and ovarian function, but also in angiogenesis. This study focuses to investigate the possibility that leptin, as an angiogenic factor, may regulate the angiogenesis during tooth development. We firstly studied the expression of leptin and vascular endothelial growth factor (VEGF) during tooth development immunohistochemically. This investigation revealed that leptin is expressed in ameloblasts, odontoblasts, dental papilla cells and stratum intermedium cells. This expression pattern was similar to that of VEGF, one of the most potent angiogenic factors. Interestingly, more leptin-positive cells were observed in the upper third portion of dental papilla, which is closest to odontoblastic layer, compared to middle and lower thirds. Moreover, in the dental papilla, more CD31 and/or CD34-positive vascular endothelial cells were observed in the vicinity of ameloblasts and odontoblasts expressing leptin and VEGF. These findings strongly suggest that ameloblasts, odontoblasts and dental papilla cells induce the angiogenesis in tooth germs by secretion of leptin as well as VEGF.
Asunto(s)
Leptina/metabolismo , Neovascularización Fisiológica , Germen Dentario/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Animales , Humanos , Inmunohistoquímica , Leptina/análisis , Ratas , Ratas Endogámicas F344 , Germen Dentario/química , Germen Dentario/crecimiento & desarrollo , Factor A de Crecimiento Endotelial Vascular/análisisRESUMEN
Melatonin is known to regulate a variety of physiological processes including control of circadian rhythms, regulation of seasonal reproductive function, regulation of body temperature, free radical scavenging, and so forth. Accumulating evidence from in vitro and in vivo experiments has also suggested that melatonin may have an influence on skeletal growth and bone formation. However, little is known about the effects of melatonin on tooth development and growth, which thus remain to be elucidated. This study was performed to examine the possibility that melatonin might exert its influence on tooth development as well as skeletal growth. Immunohistochemical analysis revealed that melatonin 1a receptor (Mel1aR) was expressed in secretory ameloblasts, the cells of the stratum intermedium and stellate reticulum, external dental epithelial cells, odontoblasts, and dental sac cells. Reverse transcription-polymerase chain reaction and Western blot analysis showed that HAT-7, a rat dental epithelial cell line, expressed Mel1aR and its expression levels increased after the cells reached confluence. These results strongly suggest that melatonin may play a physiological role in tooth development/growth by regulating the cellular function of odontogenic cells in tooth germs.