Melatonin and clinical application

Wetterberg, Lennart

doi:10.1051/rnd:19990309

Cited by 51 publications

(27 citation statements)

References 57 publications

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“…Stimulation of the HCO 3 -secretion by local intestinal melatonin seems also in line with the recent finding that melatonin increases intracellular Ca 2+ in isolated duodenal enterocytes (26) and may suggest an action at enterocyte rather than enteric nervous receptors. It should be noted that the doses of melatonin required for stimulation of duodenal HCO 3 -secretion seem much lower (>100-fold) than those tested in animal models of depressive disease (27) or used in humans for therapy of sleep disturbance or depression (28).…”

Section: Discussionmentioning

confidence: 99%

Peripheral melatonin mediates neural stimulation of duodenal mucosal bicarbonate secretion

Sjöblom¹,

Jedstedt²,

Flemström³

2001

J. Clin. Invest.

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Melatonin is released from intestinal enterochromaffin cells and from the pineal gland, but its role in gastrointestinal function is largely unknown. Our aim was to study the involvement of intestinal and central nervous melatonin in the neurohumoral control of the duodenal mucosa-protective bicarbonate secretion. Working in anesthetized rats, we cannulated a 12-mm segment of duodenum with an intact blood supply and titrated the local bicarbonate secretion with pH-stat. Melatonin and receptor ligands were supplied to the duodenum by close intra-arterial infusion. Even at low doses, melatonin and the full agonist 2-iodo-N-butanoyl-5-methoxytryptamine increased duodenal bicarbonate secretion. Responses were inhibited by the predominantly MT 2 -selective antagonist luzindole but not by prazosin, acting at MT 3 receptors. Also, luzindole almost abolished the marked rise in secretion induced by intracerebroventricular infusion of the adrenoceptor agonist phenylephrine. This response was also abolished by sublaryngeal ligation of all nerves around the carotid arteries. However, it was insensitive to truncal vagotomy alone or sympathectomy alone and was unaffected by removal of either the pineal gland or pituitary gland. Thus, melatonin stimulates duodenal bicarbonate secretion via action at enterocyte MT 2 -receptors and mediates neural stimulation of the secretion.

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Section: Discussionmentioning

confidence: 99%

Peripheral melatonin mediates neural stimulation of duodenal mucosal bicarbonate secretion

Sjöblom¹,

Jedstedt²,

Flemström³

2001

J. Clin. Invest.

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“…23 The circadian rhythm and amplitude of the nocturnal rise of melatonin has been studied in humans, and whereas intraindividual patterns of secretion are fairly predictable, comparisons of secretory patterns between individuals show considerable variation. 24 According to Wetterberg, 25 the melatonin rhythm (synthesis/secretion) is genetically determined, an opinion that has received support from studies in siblings. 26 Melatonin production gradually declines with advancing age and melatonin levels are reported to be low in elderly individuals.…”

Section: Melatonin Biosynthesismentioning

confidence: 99%

Therapeutic Actions of Melatonin in Cancer: Possible Mechanisms

et al. 2008

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189predisposing factors for the development of cancer in humans.2,3 A recent study involving 44 000 pairs of Scandinavian twins suggested that environmental factors are paramount contributors in cancer development. 4 The human body is well equipped with both immune and nonimmune anticarcinogenic mechanisms for fighting cancer. Natural killer (NK) lymphocytes play an important role in inhibiting tumor growth and metastases. 5 Many studies implicate oxidative stress in precipitating the 3 steps of carcinogenesis, that is, its initiation, promotion, and progression.6 Free radicals and reactive oxygen species (ROS) generated by environmental carcinogens, or by metabolic alterations, cause DNA damage and genetic instability. [6][7][8] DNA damage induced by oxidative stress is the major contributor to the development of malignancy. It is wellknown that natural antioxidant defenses are active in counteracting the production of free radicals and the molecular damage inflicted by them on DNA and other C ancer is a major health problem in industrialized and developing countries. Most diagnoses of cancer occur in people more than 55 years of age, with prostate cancer being the leading type of cancer in males followed by lung cancer. In females, breast and colon cancers are the leading types of cancer. Melatonin is a phylogenetically well-preserved molecule with diverse physiological functions. In addition to its well-known regulatory control of the sleep/wake cycle, as well as circadian rhythms generally, melatonin is involved in immunomodulation, hematopoiesis, and antioxidative processes. Recent human and animal studies have now shown that melatonin also has important oncostatic properties. Both at physiological and pharmacological doses melatonin exerts growth inhibitory effects on breast cancer cell lines. In hepatomas, through its activation of MT 1 and MT 2 receptors, melatonin inhibits linoleic acid uptake, thereby preventing the formation of the mitogenic metabolite 1,3-hydroxyoctadecadienoic acid. In animal model studies, melatonin has been shown to have preventative action against nitrosodiethylamine (NDEA)-induced liver cancer. Melatonin also inhibits the growth of prostate tumors via activation of MT 1 receptors thereby inducing translocation of the androgen receptor to the cytoplasm and inhibition of the effect of endogenous androgens. There is abundant evidence indicating that melatonin is involved in preventing tumor initiation, promotion, and progression. The anticarcinogenic effect of melatonin on neoplastic cells relies on its antioxidant, immunostimulating, and apoptotic properties. Melatonin's oncostatic actions include the direct augmentation of natural killer (NK) cell activity, which increases immunosurveillance, as well as the stimulation of cytokine production, for example, of interleukin (IL)-2, IL-6, IL-12, and interferon (IFN)-γ. In addition to its direct oncostatic action, melatonin protects hematopoietic precursors from the toxic effect of anticancer chemotherapeutic drugs. Melatonin secretion...

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“…Products containing melatonin are commonly used to alleviate jet lag and sleep disturbance. (6) In addition, melatonin has been mooted to possess sedative, analgesic, anxiolytic, anti-inflammatory, antioxidative and chronobiotic effects. (7)(8)(9) A qualitative systematic review of ten studies demonstrated that it was effective in decreasing preoperative anxiety as compared to a placebo, except in the elderly population.…”

Section: Introductionmentioning

confidence: 99%

Melatonin premedication versus placebo in wisdom teeth extraction: a randomised controlled trial

Seet

Liaw

Tay

et al. 2015

smedj

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INTRODUCTIONPain after wisdom teeth surgery can be moderate in severity and is compounded by preoperative anxiety in young patients. We studied the effect of melatonin premedication on postoperative pain and preoperative anxiety in patients undergoing wisdom teeth extractions. METHODSThis randomised controlled trial recruited 76 patients at Khoo Teck Puat Hospital who were American Society of Anesthesiologists physical status I and II, aged 21 to 65 and scheduled to undergo elective extraction of all four wisdom teeth under general anaesthesia. Patients with a history of long-term use or allergy to melatonin were excluded. The patients received either 6 mg melatonin or a placebo 90 minutes before surgery. Visual analogue scale (VAS) scores at multiple time intervals for postoperative pain and preoperative anxiety, patient satisfaction and first-night sleep quality scores were obtained. Mixed-effects regression models were used for longitudinal analysis of VAS pain, anxiety and satisfaction scores.RESULTS Maximum VAS scores for pain and anxiety were 18.6 ± 19.1 mm at 60 minutes postoperatively and 26.2 ± 23.4 mm at 90 minutes preoperatively, respectively. After adjusting for gender, female patients who received melatonin had a faster rate of reduction of VAS pain (p = 0.020) and anxiety scores (p = 0.003) over time compared to the placebo group. No such effect was demonstrated in male patients. There was no significant difference in sleep quality or satisfaction scores.CONCLUSION Melatonin use did not consistently contribute to pain and anxiety amelioration in all patients. Our study demonstrated a positive effect in female patients, suggestive of sexual dimorphism.

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Melatonin and clinical application

Cited by 51 publications

References 57 publications

Peripheral melatonin mediates neural stimulation of duodenal mucosal bicarbonate secretion

Peripheral melatonin mediates neural stimulation of duodenal mucosal bicarbonate secretion

Therapeutic Actions of Melatonin in Cancer: Possible Mechanisms

Melatonin premedication versus placebo in wisdom teeth extraction: a randomised controlled trial

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