Latest medical literature on melatonin

Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new melatonin research articles will be listed here shortly after becoming available to us.

Medical research on melatonin

Assessment of different sample processing procedures applied to the determination of melatonin in plants.

Phytochem Anal. 2008 Jul 11;
Arnao MB, Hernández-Ruiz J
Introduction - Melatonin, an indoleamine well known in vertebrates and structurally related to other important substances such as tryptophan or indole-3-acetic acid, is also present in the plant kingdom although its specific function(s) remain to be established. The emerging field of melatonin studies in plants has progressed very slowly, mainly due to the problems associated with melatonin quantification in plants.Objective - Two commonly used procedures for plant samples are compared. The analytical characteristics of both procedures are quantitatively presented using different solvents and small amounts of fresh biological material, and the respective recovery rates and quantitative limits are presented. Some improvements are suggested.Methodology - Two different sample extraction procedures were compared: a direct-sample extraction (DSE) and a homogenised- sample extraction (HSE). Melatonin was then determined in the respective plant samples by HPLC with fluorescence detection.Results - Using the DSE procedure, more than 94% melatonin was recovered from standard solutions, whereas levels higher than 93% were recovered from the spiked plant samples, with little difference between ethyl acetate and chloroform extractions. In the case of HSE, the recoveries of melatonin were approximately half and never higher than 55%. The ultrasonic treatment proposed in the DSE procedure showed different levels of efficiency (2-20%), depending on the sample.Conclusion - This study has established that, with the direct sample extraction procedure, higher recovery rates are obtained both in standard solutions and in plant samples. The straightforwardness and reproducibility of the extraction procedure is accompanied by the high sensitivity obtained with fluorescence detection. Copyright (c) 2008 John Wiley & Sons, Ltd.

Melatonin: a new treatment for endometriosis.

Reprod Biomed Online. 2008 Jul; 17(1): 135

Premedication with melatonin vs midazolam in anxious children.

Paediatr Anaesth. 2008 Jul; 18(7): 635-41
Isik B, Baygin O, Bodur H
Aim: Failure of dental treatment caused by anxiety is a common problem in children. Oral midazolam has been the most commonly used premedication for pediatric patient but the use of midazolam may be associated with paradoxical reactions in children. Melatonin may induce a natural sleepiness and improve sedation. We have investigated premedication with melatonin compared with midazolam in children under nitrous oxide/oxygen (N(2)O/O(2)) sedation for dental treatment. Methods: In a randomized study, 60 children received either 3 mg of melatonin [Melatonina (3 mg(R)) 60 min before the procedure (n = 15); group I], 0.5 mg.kg(-1) melatonin 60 min before the procedure (n = 15; group II), 0.75 mg.kg(-1) midazolam [Dormicum (15 mg/3 ml (R)) 15 min before the procedure (n = 15); group III] or 3 ml of 0.09 NaCl 15 min (n = 7) or 60 min before the procedure (n = 8; group IV) orally. The children were sedated with 40/60% N(2)O/O(2) inhalation. The heart rate and O(2) saturation were monitored during the treatment period. The level of sedation was assessed according to the Ramsay Sedation Scale. The children's sedation success during dental treatment was classified. The sedation success and other sedation-related events recorded. Comparisons among the four groups were made using one-way anova or Kruskal-Wallis test, and if any significant differences were noted, the Tukey's HSD or Mann-Whitney U-test were used for intergroup comparisons. All differences were considered significant at P < 0.05. Results: The evaluation of sedation success was as follows: group I: satisfactory (n = 1), average satisfactory (n = 4), and unsatisfactory (n = 10); group II: satisfactory (n = 2), average satisfactory (n = 3), and unsatisfactory (n = 10); group III: satisfactory (n = 9), average satisfactory (n = 6); and group IV: satisfactory (n = 1), average satisfactory (n = 3), and unsatisfactory (n = 11). Conclusion: In these doses and clinical conditions, melatonin was similar to that of placebo and did not contribute to N(2)O/O(2) sedation of anxious children.

Melatonin for the treatment of gastroesophageal reflux disease.

Altern Ther Health Med. 2008 Jul-Aug; 14(4): 54-8
Werbach MR
The enterochromaffin cells of the gastrointestinal (GI) tract secrete 400 times as much melatonin as the pineal gland; therefore, it is not surprising that research is finding that this indole plays an important role in GI functioning. In animal studies, it protects against GI ulcerations, and randomized clinical trials suggest its efficacy in treating functional dyspepsia and irritable bowel syndrome. Melatonin administration has been shown to protect against esophageal lesions in animals. Moreover, in a randomized, single-blind clinical trial of subjects with gastroesophageal reflux disease (GERD), the combination of melatonin with other natural supplements was found to be superior to omeprazole, a proton pump inhibitor (PPI). Its administration as a single treatment for GERD has not been previously reported. A 64-year-old Caucasian female who required treatment with a PPI for symptoms of GERD wished to substitute a natural treatment because of the risk of worsening her osteoporosis. She experienced a return of symptoms following each of three 20-day trials of a proprietary blend of D-limonene when attempts were made to discontinue the PPI. She then underwent a trial of a natural formula consisting of melatonin 6 mg, 5-hydroxytryptophan 100 mg, D,L-methionine 500 mg, betaine 100 mg, L-taurine 50 mg, riboflavin 1.7 mg, vitamin B6 0.8 mg, folic acid 400 microg, and calcium 50 mg. After 40 days, the PPI was withdrawn without a return of symptoms. Subsequently, an attempt to reduce melatonin to 3 mg resulted in symptoms, while all other ingredients were withdrawn with minimal symptoms during 10 months of follow-up.

The effects of melatonin on glutathione peroxidase activity in serum and erythrocytes after adriamycin in normal and pinealectomised rats.

Endokrynol Pol. 2008 May-Jun; 59(3): 200-6
Dabrowska K, Stuss M, Gromadzińska J, Wasowicz W, Sewerynek E
Introduction: Adriamycin (ADR) is a potent chemotherapeutic agent, effective in the treatment of leukaemias, lymphomas and many solid tumours. However, its clinical usage is often limited by cardiotoxicity, induced by oxygen radical damage of the membrane lipids. Melatonin (MEL) is a well-known antioxidant. It has been shown that MEL can scavenge free radicals, both directly and indirectly, stimulating the activity of antioxidative enzymes such as glutathione peroxidase (GSH-Px). The aim of the study: The aim of the study was to examine the effect of MEL on serum and erythrocyte GSH-Px activity after ADR in normal and pinealectomised rats. Material and methods: Wistar rats were divided into the three groups: control animals (Intact), sham-operated (Sham-PX) and pinealectomised (Px). Each of the groups was divided into four subgroups, injected with: 1 - saline, 2 - MEL, 3 - ADR and 4 - ADR + MEL. ADR was administered 2 months after Px as a single dose (15 mg/kg, i.p.) 1 hour after the fourth melatonin injection. Melatonin (5 mg/kg, i.p.) was administered for 4 days before and 2 days after ADR. After 6 days of treatment, the rats were killed by decapitation. Their blood was collected for measurements. Results: In serum GSH-Px activity decreased in all the groups after ADR. Pinealectomy decreased the activity of the enzyme in all the groups of animals examined. In erythrocytes GSH-Px decreased after ADR in the Px-animals. The effect of pinealectomy on erythrocyte GSH-Px activity was not as strongly expressed as serum GSH-Px activity. MEL did not change GSH-Px activity after ADR. Conclusion: Melatonin, in pharmacological concentrations, did not influence the activity of GSH-Px, either in normal or in pinealectomised rats after ADR. A deficiency of endogenous melatonin production may inhibit GSH-Px activity.

Letter to the editor.

Dev Med Child Neurol. 2008 Jul; 50(7): 558
Jan JE, Wasdell MB

A study of immunoendocrine strategies with pineal indoles and interleukin-2 to prevent radiotherapy-induced lymphocytopenia in cancer patients.

In Vivo. 2008 May-Jun; 22(3): 397-400
Lissoni P, Rovelli F, Brivio F, Fumagalli L, Brera G
BACKGROUND: Lymphocytopenia represents one of the most evident side-effects of radiotherapy (RT), particularly in the case of irradiation of pelvis, since it is the main location of bone-marrow proliferating cells in adults. Because of the fundamental role of lymphocytes in suppressing anticancer immunity, RT-induced lymphocytopenia could negatively influence the prognosis of cancer patients and the therapeutic efficacy of RT itself. In experimental conditions, the biological toxicity of irradiation appeared to be reduced by antioxidant agents, such as pineal hormones melatonin. A preliminary study was conducted to evaluate the influence of different immunobiological strategies with pineal indoles melatonin (MLT), 5 methoxytriptamine (5-MTT) or low-dose IL-2, the lymphocyte growth factor, on pelvic irradiation-induced lymphocytopenia in cancer patients suffering from rectal cancer or uterine cervix carcinoma. PATIENTS AND METHODS: The study included 20 consecutive patients, who underwent pelvic irradiation for a total dose of 50.4 Gy. The patients were randomized to be concomitantly treated with MLT alone, with MLT plus 5-MTT or with s.c. low-dose IL-2 . RESULTS: RT induced a significant decline in the mean number of lymphocytes while neither MLT alone, nor MLT plus 5-MTT were able to significantly reduce this decline. Conversely, IL-2 caused a statistically significant reduction of the RT-induced effect, so that the mean number of lymphocytes was significantly higher in patients concomitantly treated by IL-2 than in the other groups. CONCLUSION: This preliminary study showed that low-dose IL-2 was sufficient to reduce, even though not to completely abrogate, RT-induced lymphocytopenia. Further studies with different schedules and doses of IL-2 will be required to optimize the protective effect of IL-2 on irradiation-induced lymphocytopenia in humans.

The effect of melatonergic and non-melatonergic antidepressants on sleep: weighing the alternatives.

World J Biol Psychiatry. 2008 Jan 4; 1-13
Pandi-Perumal SR, Trakht I, Srinivasan V, Spence DW, Poeggeler B, Hardeland R, Cardinali DP
In DSM-IV the occurrence of disturbed sleep is one of the principal diagnostic criteria for major depressive disorder (MDD). Further, there is evidence of reciprocity between the two conditions such that, even in the absence of current depressive symptoms, disturbed sleep often predicts their development. The present review discusses the effects of antidepressants on sleep and evaluates the use of the recently developed melatonin agonist-selective serotonin antagonists on sleep and depression. Although many antidepressants such as the tricyclics, monoamine oxidase inhibitors, serotonin-norepinephrine reuptake inhibitors, several serotonin receptor antagonists and selective serotonin reuptake inhibitors (SSRIs) have all been found successful in treating depression, their use is often associated with a disruptive effect on sleep. SSRIs, currently the most widely prescribed of the antidepressants, are well known for their instigation or exacerbation of insomnia. The recently introduced novel melatonin agonist and selective serotonin antagonist antidepressant, agomelatine, which has melatonin MT(1) and MT(2) receptor agonist and 5-HT(2c) antagonist properties, has been useful in treating patients with MDD. Its rapid onset of action and effectiveness in improving the mood of depressed patients has been attributed to its ability to improve sleep quality. These properties underline the use of melatonin analogues as a promising alternative for the treatment of depression.

Measurement of antioxidant ability of melatonin and serotonin by the DMPD and CUPRAC methods as trolox equivalent.

J Enzyme Inhib Med Chem. 2008 Jun 2; 1
Gulcin I
Melatonin (N-acetyl-5-methoxytryptamine) is the chief secretory product of the pineal gland and synthesized enzymatically from serotonin (5-hydroxytryptamine). These indoleamine derivatives play an important role in the prevention of oxidative damage. In the present study, DMPD radical scavenging and cupric ion (Cu(2+)) reducing ability of melatonin and serotonin as trolox equivalent antioxidant activity (TEAC) was investigated. Melatonin and serotonin demonstrated 73.5 and 127.4 mug/mL trolox equivalent DMPD( radical+) scavenging activity at the concentration of 100 mug/mL. Also, at the same concentration, melatonin and serotonin showed 14.41 and 116.09 mug/mL trolox equivalent cupric ion (Cu(2+)) reducing ability. These results showed that melatonin and serotonin had marked DMPD( radical+) radical scavenging and cupric ions (Cu(2+)) reducing ability. Especially, serotonin had higher DMPD radical scavenging and cupric ions (Cu(2+)) reducing activity than melatonin because of its phenolic group.

Hormonal carcinogenesis and sociobiological development factors in endometrial cancer: a systematic review.

Acta Obstet Gynecol Scand. 2008 Jun 18; 1-12
Andrea T, Daniele V, Roberta M, Giuseppe L, Antonio M, Raffaele T
Background. Endometrial cancer (EC) is one of the most common invasive gynecologic malignancy in developed countries and represents the eighth leading cause of death for cancer in women; it typically arises in the sixth or seventh decade of life, with a mean age at diagnosis of 61 years and many seem to be the biological and social factors that predispose to EC development. Objectives. Aim of this systematic review was to evaluate the possible roles of genetic and sociobiological development factors in type I EC. Review methods. the authors performed a Medline literature research for the years 2000-2007, of relevant clinical trials, collecting information from scientific researches; the authors mentioned also other EC risk factors, without deepening these last aspects, but focusing our attentions on the more relevant and recent ones. Results. Several sociobiological and lifestyle characteristics, such as hormone replacement therapy, glycemic index, obesity, alcohol, antipsychotic, melatonin, physical activity and variants in hormone metabolism genes have been identified as risk factors for developing EC; the majority of these factors are associated with excess estrogens, which may cause continued stimulation of the endometrium leading to endometrial hyperplasia and possible progression to cancer. Moreover, Hereditary Nonpolyposis Colorectal Cancer syndrome, a genetic and allelic polymorphisms of the genes involved in the estrogens metabolism, may contribute to predisposition to EC. A possible association between several polymorphisms and EC risk has been evaluated in different studies with some conflicting results. Conclusions. Many factors can influence EC etiology; among these it is well established that endogenous and exogenous estrogens stimulation can promote the proliferation of cells and influence the EC risk, acting on other external factors. Further studies are needed to arrive to a better understating of EC etiology and predisposition.