Melatonin as a chronobiotic/cytoprotective agent in bone: doses involved
Abstract: Because the chronobiotic and cytoprotective molecule melatonin diminishes with age, its involvement in postmenopausal and senescence pathology has been considered since long. One relevant melatonin target site in aging individuals is bone where melatonin chronobiotic effects mediated b...
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| Formato: | Artículo |
| Lenguaje: | Inglés |
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John Wiley & Sons
2024
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| Acceso en línea: | https://repositorio.uca.edu.ar/handle/123456789/18301 |
| Aporte de: |
| Sumario: | Abstract:
Because the chronobiotic and cytoprotective molecule melatonin diminishes
with age, its involvement in postmenopausal and senescence pathology has
been considered since long. One relevant melatonin target site in aging
individuals is bone where melatonin chronobiotic effects mediated by MT1
and MT2 receptors are demonstrable. Precursors of bone cells located in bone
marrow are exposed to high quantities of melatonin and the possibility arises
that melatonin acts a cytoprotective compound via an autacoid effect. Proteins
that are incorporated into the bone matrix, like procollagen type I c‐peptide,
augment after melatonin exposure. Melatonin augments osteoprotegerin, an
osteoblastic protein that inhibits the differentiation of osteoclasts. Osteoclasts
are target cells for melatonin as they degrade bone partly by generating free
radicals. Osteoclast activity and bone resorption are impaired via the free
radical scavenger properties of melatonin. The administration of melatonin in
chronobiotic doses (less than 10 mg daily) is commonly used in clinical studies
on melatonin effect on bone. However, human equivalent doses allometrically
derived from animal studies are in the 1–1.5 mg/kg/day range for a 75 kg
human adult, a dose rarely used clinically. In view of the absence of toxicity of
melatonin in phase 1 pharmacological studies with doses up to 100 mg in
normal volunteers, further investigation is needed to determine whether high
melatonin doses have higher therapeutic efficacy in preventing bone loss. |
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