Prospects of the Clinical Utilization of Melatonin

Abstract

This review summarizes the present knowledge on melatonin in several areas on physiology and discusses various prospects of its clinical utilization. Ever increasing evidence indicates that melatonin has an immuno-hematopoietic role. In animal studies, melatonin provided protection against gram-negative septic shock, prevented stress-induced immunodepression, and restored immune function after a hemorrhagic shock. In human studies, melatonin amplified the antitumoral activity of interleukin-2. Melatonin has been proven as a powerful cytostatic drug in vitro as well as in vivo. In the human clinical field, melatonin appears to be a promising agent either as a diagnostic or prognostic marker of neoplastic diseases or as a compound used either alone or in combination with the standard cancer treatment. Utilization of melatonin for treatment of rhythm disorders, such as those manifested in jet lag, shift work or blindness, is one of the oldest and the most successful clinical application of this chemical. Low doses of melatonin applied in controlled-release preparation were very effective in improving the sleep latency, increasing the sleep efficiency and rising sleep quality scores in elderly, melatonin-deficient insomniacs. In the cardiovascular system, melatonin seems to regulate the tone of cerebral arteries; melatonin receptors in vascular beds appear to participate in the regulation of body temperature. Heat loss may be the principal mechanism in the initiation of sleepiness caused by melatonin. The role of melatonin in the development of migraine headaches is at present uncertain but more research could result in new ways of treatment. Melatonin is the major messenger of light-dependent periodicity, implicated in the seasonal reproduction of animals and pubertal development in humans. Multiple receptor sites detected in brain and gonadal tissues of birds and mammals of both sexes indicate that melatonin exerts a direct effect on the vertebrate reproductive organs. In a clinical study, melatonin has been used successfully as an effective female contraceptive with little side effects. Melatonin is one of the most powerful scavengers of free radicals. Because it easily penetrates the blood-brain barrier, this antioxidant may, in the future, be used for the treatment of Alzheimer’s and Parkinson’s diseases, stroke, nitric oxide, neurotoxicity and hyperbaric oxygen exposure. In the digestive tract, melatonin reduced the incidence and severity of gastric ulcers and prevented severe symptoms of colitis, such as mucosal lesions and diarrhea.

Melatonin: A pleiotropic molecule regulating inflammation

“…Melatonin was investigated in a prospective clinical trial regarding antioxidant therapy to inhibit the action of nitro-oxidative stress [133]. It was demonstrated that nitric oxide (NO) plays an important role in septic shock, an acute inflammatory response [134]. Indeed, melatonin improves the survival of mice with LPS-induced shock by -11 -reducing NO synthesis via its antioxidant and anti-apoptotic properties [135].…”

“…Melatonin was shown to improve clinical outcome in terms of infection and organ failure in randomized clinical trials, thus being a promising antioxidant molecule in antioxidant therapy to combat sepsis [132][133][134]137].…”

Lighting for the human circadian clock: recent research indicates that lighting has become a public health issue

“…Without a normal cycle of MLT inhibition and production responding to cycles of light and dark, human health may be negatively affected (5,22,29,38,47,54,57,60,61,76).…”

Investigation of the effect of intracolonic melatonin gel formulation on acetic acid-induced colitis

“…High melatonin concentrations are found in the gastrointestinal tract and enterochromaffin cells have been suggested as the source of its synthesis (Bubenik et al, 1998). It is known that melatonin and its metabolites are potent antioxidants, both as direct free radical scavengers and as indirect antioxidants (Tan et al, 1994;Reiter et al, 2007;Rybka et al, 2014).…”