Doses Of Melatonin Research Articles

Cardioprotective effects of novel antioxidants post-myocardial infarction: An integrative review of preclinical and clinical data

Myocardial infarction (MI), is still a major public health problem, and oxidative stress contributes to the degree of myocardial damage after MI. Oxygen-derived free radicals (ODFR) worsen myocardial injury and result in chronic heart failure in many patients. These harms have led to interest in antioxidant treatment to reduce these adverse effects; new antioxidants with the potential for cardioprotection are the subject of significant interest. This review summarizes basic and clinical research comparing the effectiveness of newly synthesized antioxidants in attenuating oxidative stress and enhancing recovery after myocardial infarction. The review synthesizes evidence of a reduction in infarct size, enhancement of cardiac function, and repression of apoptosis in myocardial cells by the use of antioxidants from animal models. Melatonin, N-acetylcysteine, edaravone, and coenzyme Q10 demonstrated a wide range of preclinical positive effects by acting as ROS free radicals scavengers, modulating mitochondria dysfunction, and reducing inflammation. These findings are extrapolated from humans, although advances in antioxidant therapy are beginning to be viewed in initial clinical trials. From human data, although clinical trials are scarce, the evidence of new antioxidants can improve point and long-term outcomes in patients undergoing MI, help to increase the contractility of the injured myocardium, and decrease the mortality level. However, some issues are still there, such as high inter- and intra-individual variability in patient response and dosing schedule, as well as adverse effects such as pro-oxidant activity at high Oral administered doses of melatonin. The limitations of the current research discussed in this review include the general lack of large-scale, well-controlled clinical trials and the need for long-term follow-up studies. This review also proposed future research directions for improving antioxidant applications in post-MI management.

Administration of melatonin nanoparticles improves testicular blood flow, echotexture of testicular parenchyma, scrotal circumference, and levels of estradiol and nitric oxide in prepubertal ossimi rams under summer heat stress.

Environmental heat stress (HS) impairs reproductive efficiency in farm animals. This study investigated, for the first time, how the melatonin and melatonin nanoparticles treatment affected the testicular hemodynamics, testicular volume, echotexture [Pixel intensity (PIX) and integrated density (IND)], scrotal circumference, serum concentration of testosterone (T), estradiol (E2), nitric oxide (NO), and total antioxidant capacity (TAC) in prepubertal Ossimi ram lambs in hot climatic conditions. The lambs undergoing examination had a temperature humidity index (THI) of 87.05 ± 1.70, indicating severe HS condition. Fifteen prepubertal Ossimi ram lambs were exposed to a single s.c injection of either nano melatonin (nano melatonin group; 20mg/ram; n = 5) or melatonin suspended in two ml of corn oil (melatonin group; 40mg/ram; n = 5) or two ml of corn oil (control group; n = 5). Blood collection and ultrasonographic assessment of the testes and supratesticular arteries (STAs) were conducted immediately before treatment (W0) and once weekly for six successive weeks after nano melatonin and melatonin injection (W1-W6). Results revealed decreases (P < 0.05) in the Doppler indices (resistive index; RI and pulsatility index; PI) of the testicular arteries at most time points of the study in the nano melatonin and melatonin groups. PIX of testicular parenchyma was significantly increased (P ˂ 0.05) in the treated groups compared to the control one. IND of testicular parenchyma increased significantly in the nano melatonin group compared to the melatonin and control groups. Testicular volume and scrotal circumference significantly increased (P < 0.05) in nano melatonin and melatonin groups compared to the control one. T concentration did not significantly (P > 0.05) change in the treated groups compared to the control group. E2, NO, and TAC concentrations increased (P < 0.05) in the treated groups compared to the control one. In conclusion, this study extrapolated that administrations of melatonin or nano melatonin can ameliorate the effects of environmental HS in prepubertal Ossimi ram lambs with a more protective effect and lower dose of nano melatonin.

Exogenous Melatonin as Pre- and Postharvest Application on Quality Attributes, Antioxidant Capacity, and Extension of Shelf Life of Papaya

Papaya is widely grown in tropical and subtropical climates due to its high yield potential and high returns. The vital hormone melatonin, regulating various biological processes in plants, is eco-friendly and less harmful to humans than other chemicals. This study aims to enhance the quality and antioxidant enzyme activities and lessen postharvest senescence in papaya cv. CO 8 fruits during both ambient (32 ± 2 °C and 55 ± 5% RH) and cold storage (10 ± 2 °C and 90–95% RH) as exogenous melatonin (EMT) is applied in varying concentrations. An optimum melatonin dose of 1.5 mM was applied as a pre-harvest spray 15 days before harvest and a postharvest dip proved effective in prolonging shelf life (under ambient it prolonged to day 9 and under cold storage up to 28 days) and delaying ripening and softening. Exogenous melatonin application enhanced antioxidant activity, reduced weight loss, maintained firmness, delayed ripening enzymes, and lowered ethylene and CO2 levels. For instance, control fruits had weight losses between 7.42% and 10.09%, while fruits treated with 1.5 mM melatonin showed 5.74% and 9.06% weight loss under ambient and cold storage, respectively. In conclusion, applying EMT (1.5 mM) could be an economically viable and environmentally benign way to lessen senescence after harvest and preserve the qualities of the papaya fruit during ambient and cold storage.

Gabapentin for Delirium in Infants in the Neonatal Intensive Care Unit

OBJECTIVE A protocol was developed for neonatal intensive care unit (NICU) delirium: Step 1, gabapentin for pain or melatonin for sleep; Step 2, add on other Step 1 agent; Step 3, antipsychotics. The purpose of this study was to describe the utility and dosing of gabapentin for NICU delirium. METHODS Retrospective evaluation of NICU patients from January 1, 2021–December 31, 2022 who received &amp;gt;1 dose of gabapentin based on the delirium protocol. Data collection included demographics, gabapentin regimen, and concomitant sedatives and analgesics. The primary objective was to identify the number of patients receiving gabapentin for Step 1 or Step 2. Secondary objectives included identifying the number of patients requiring antipsychotics (Step 3), the gabapentin regimen, comparison of Échelle de Douleur et d'Inconfort du Nouveau-né (EDIN), Cornell Assessment of Pediatric Delirium (CAPD), and Withdrawal Assessment Tool-1 (WAT-1) scores 72 hours pre- and post-gabapentin initiation, and comparison of opioids, clonidine, and melatonin 24 hours pre- and 72 hours post-gabapentin initiation. Wilcoxon signed rank tests were employed with significance defined at p &amp;lt; 0.05. RESULTS Twenty-nine patients were studied. The majority (n = 22; 75.9%) received gabapentin for Step 1; no patients required Step 3. The median initial dose was 14.4 mg/kg/day divided every 8 hours. Twelve (41.4%) required increase to a median of 16.9 mg/kg/day. A significant decrease in EDIN and WAT-1 scores was noted, but there was no change in CAPD scores or opioid, clonidine, or melatonin doses pre- versus post-gabapentin. CONCLUSION The majority received gabapentin at a median dose of 14 mg/kg/day as Step 1 for delirium. Gabapentin was associated with a significant decrease in pain and withdrawal scores.

Effects of Melatonin on Sleep Quality and Patient-Reported Outcomes After Arthroscopic Rotator Cuff Surgery: A Prospective Randomized Controlled Trial.

Sleep disturbance is a significant symptom associated with both rotator cuff tears and arthroscopic rotator cuff repair. Melatonin has been shown to be safe and effective in managing multiple sleep disorders, including secondary sleep disorders, with relatively minor adverse effects and lack of addictive potential. To investigate the effects of oral melatonin on postoperative sleep quality after arthroscopic rotator cuff repair. Randomized controlled trial; Level of evidence, 1. This was a prospective randomized clinical trial evaluating patients undergoing arthroscopic rotator cuff repair. Exclusion criteria included history of alcohol abuse, current antidepressant or sedative use, revision rotator cuff repair, severe glenohumeral arthritis, and concurrent adhesive capsulitis. Patients were randomly assigned in a 1:1 ratio to 1 of 2 groups: 5-mg dose of melatonin 1 hour before bedtime or standard sleep hygiene (≥6 hours per night, avoiding caffeine and naps in the evening). Patients in the melatonin group took their assigned melatonin dose for 6 weeks beginning the day of surgery. Patient-reported outcome assessments, including the Pittsburgh Sleep Quality Index (PSQI), the American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES), and the Single Assessment Numeric Evaluation (SANE), and pain medication charts were collected preoperatively as well as at 2 weeks, 6 weeks, 3 months, 4 months, and 6 months postoperatively. Numeric variables were analyzed using paired and unpaired t tests, with significance set at P < .05. Eighty patients were included for final analysis (40 in the control group, 40 in the melatonin group). Patient characteristics such as age, sex, race, body mass index, and laterality did not differ significantly (P≥ .05). Preoperative ASES, SANE, and PSQI scores did not differ between groups (P≥ .055). PSQI scores were significantly lower (better quality sleep) in the melatonin group at the 6-week postoperative period (P = .036). There was a positive correlation between how patients rated the intensity of their pain and the PSQI at the 6-week postoperative period (0.566). The PSQI question regarding sleep quality was found to be significantly lower in the melatonin group at the 3-month, 4-month, and 6-month postoperative periods (P = .015, P = .041, and P≤ .05, respectively). SANE scores were significantly lower in the melatonin group (P = .011) at 6 weeks and then higher in the melatonin group (P = .017) at 6 months. ASES scores were significantly higher in the melatonin group at 4 and 6 months (P = .022 and P = .020, respectively). Lastly, patients who were randomized into the melatonin group were found to use significantly less narcotic medication at the 4-month postoperative period (P = .046). Melatonin use after arthroscopic rotator cuff repair led to improved sleep quality (PSQI) in the early postoperative period as well as improved functional outcomes (ASES and SANE scores) and decreased narcotic use in the later postoperative period. Patients with significant sleep disturbances associated with rotator cuff repairs may benefit from the use of melatonin. NCT04278677 (ClinicalTrials.gov identifier).

Investigation of the effects of melatonin application on storage in plums (Prunus domestica L.) grown under organic and conventional conditions

This study was carried out to investigate the effects of melatonin applications on postharvest quality changes of organic and conventionally grown plum fruit. Melatonin was applied in 0, 50, and 100 µmol L− 1 for organic and conventional samples. The fruits were stored at + 2.0 °C and 90% relative humidity for 28 days. During the storage period, the color, weight loss, firmness, Soluble solids concentration (SSC), titratable acidity (TA), pH, total antioxidant content, and total phenolics were evaluated at 7-day intervals. While no effect of melatonin applications on weight loss of organically grown plums was observed, it was determined that weight loss decreased as the dose of melatonin increased in conventionally grown plums. The lowest weight loss during storage was determined in conventionally grown plums treated with 100 µmolL− 1 melatonin. It was observed that the firmness values decreased as the storage period increased in both cultivation methods. The firmness decreased as the dose of melatonin application increased in organically grown plums, while the firmness increased as the dose of melatonin application increased in conventional cultivation. Melatonin application did not positively affect SSC, pH, and color values. However, it was determined that the mean TA values decreased as the dose of melatonin increased in both cultivation methods. When the total phenol content of organic and conventional plums was examined, it was determined that melatonin application decreased the number of phenolic compounds. The highest phenolic content was determined in the control samples. The total amount of antioxidants was 1.71 µmol TE g− 1 on the 28th day in the highest (100 µmol L− 1) melatonin-treated conventionally grown plums.

Meta-Analysis of Experimental Studies of the Effect of Melatonin Monotherapy on Body Weight Gain and Eating Behavior in Rats on Different Diets

In an earlier meta-analysis, we showed that long-term melatonin administration minimizes diet-induced changes in lipid profiles. The purpose of our present work was to use a meta-analysis to investigate the effect of melatonin monotherapy on body weight gain (BWG) and eating behavior in rats depending on diet. To this end, we conducted a meta-analysis of 43 publications examining the effects of melatonin monotherapy on BWG, leptin levels, food and water intake in rats fed a standard diet (37 publications), as well as high-fructose diets (5 publications) and fats (9 publications). Our findings suggest that although melatonin reduced the level of triglycerides, total cholesterol and leptin in rats fed high-fructose and high-fat diets but not those fed a standard diet, melatonin treatment prevented BWG in rats on either diet. Increasing the dose of melatonin did not enhance the effect of therapy with any of the diets studied. We did not obtain convincing evidence that the effect of melatonin depends on the initial body weight and age of rats. On a standard diet, melatonin has been found to reduce food and water intake. Melatonin did not reduce BWG with a standard diet when administered intraperitoneally. Our research suggests that melatonin may be beneficial for diet-induced metabolic disorders by improving lipid profiles and preventing BWG. However, a decrease in appetite and BWG when taking melatonin may also be associated with negative side effects of the drug, which requires further research.

Anti-browning action of melatonin is dependent on the type of tissue in minimally processed sweet potatoes

This study explored the impact of exogenous melatonin on oxidative damage, protective mechanisms against oxidation, and reactions leading to browning, as well as the accumulation of antioxidants in minimally processed white-fleshed and orange sweet potato roots. Sweet potato roots with white and orange pulp were subjected to minimal processing and immersion in melatonin solutions at concentrations of 0, 10, 100, and 1000 µmol L−1. Following packaging, these were stored at 5 ± 2 °C for 20 days. Results indicate that increasing melatonin concentrations significantly reduced browning symptoms in both white and orange sweet potato slices. This reduction was associated with decreased levels of hydrogen peroxide (H2O2), thiobarbituric acid-reactive substances (TBARs), and electrolyte leakage, indicating reduced cell membrane damage. Enhanced protection was observed through increased activity of antioxidant enzymes superoxide dismutase, catalase, and ascorbate peroxidase and higher levels of antioxidant metabolites, including vitamin C and phenolic compounds, as confirmed by in vitro assays for antioxidant capacity (FRAP and DPPH), however, the levels of total carotenoids, anthocyanins, and yellow flavonoids did not show a significant difference between the melatonin treatments. Notably, sweet potato slices treated with higher melatonin doses of 100 and 1000 µmol L−1 exhibited reduced phenylalanine ammonia-lyase activity and phenolic compound accumulation. This effect, coupled with lower polyphenol oxidase (PPO) and peroxidase (POD) activities, likely contributed to prolonged preservation quality by maintaining cellular redox homeostasis.

Combined swimming with melatonin protects against behavioural deficit in cerebral ischemia-reperfusion injury induced rats associated with modulation of Mst1– MAPK ‐ERK signalling pathway

Background The inconvenience of social and behavioural deficits after cerebral ischaemia reperfusion (I/R) injury is still not well documented. Aim We aimed to study the protective effect of preconditioning swimming exercise combined with melatonin against cerebral I/R induced injury. Methodology Sixty rats were allocated into 6 groups; groups I and II served as control. Groups 3,4,5,6 subjected to bilateral carotid ligation for 30 minutes (min.) followed by reperfusion. Group 3 left untreated while groups 4 and 6; underwent swimming exercise 30 min/day, five days a week for three weeks before the surgery. Groups 5 and 6 treated with melatonin 30 minutes before the operation, then, all rats in groups 4, 5,6 were subjected to I/R. After that, groups 5 and 6 treated with 2nd dose of melatonin 30 minutes after reperfusion. Results Combined strategy exhibited the most neuroprotective effect through prevention of cerebral I/R induced inflammation, oxidative stress and apoptosis with subsequent improvement in socio behaviour deficits and enhanced Glial cell proliferative capacity. Conclusion The protective contribution of combined strategy is associated with modulation in Macrophage‐stimulating 1/mitogen-activated protein kinase/extracellular signal-regulated kinase (MST1/MAPK/ERK) pathway which may explain, at least in part, its protective potential.

Effect of melatonin supplementation upon parental care and nestling growth in arctic-breeding songbirds.

Arctic-breeding birds exhibit around-the-clock activity, and these activity cycles are postulated to maximize reproductive success during the short breeding season characteristic of high-latitude regions. Two closely related species of arctic-breeding songbirds, Lapland longspurs (Calcarius lapponicus; ground-nesting) and snow buntings (Plectrophenax nivalis; cavity-nesting) exhibit extended activity cycles throughout the polar day (71° N) except for 4-5 h of daily quiescence. Ground-nesting Lapland longspurs experience higher levels of nest predation than cavity-nesting snow buntings, and this difference is reflected in elevated nest vigilance in male longspurs compared with snow buntings. In this study, we examined the effect of melatonin supplementation upon male parental care, corresponding measures of nestling growth, and ability to reduce activity (and increase sleep). A pharmacological dose of melatonin in captive snow buntings dampened the amplitude of activity rhythms over the polar day with no detectable phase-shifting compared with control-implanted birds. Melatonin treatment reduced nest visits and overall time spent on the nest by male snow buntings compared with controls. There was no significant increase in time spent by female snow buntings on the nest to compensate for this, and there was no significant effect on offspring growth rates. There were no effects of melatonin supplementation on longspur adults or offspring, suggesting behavioral insensitivity to exogenous melatonin treatment. These differences in sensitivity underscore the importance of nest defense in ground-nesting longspurs compared with cavity-nesting snow buntings, which participate minimally in nest defense.

Investigation of the therapeutic effect of melatonin on deltamethrin applied mouse primary hepatocyte culture

Objective In recent years, it has been known that the melatonin hormone, secreted from the pineal gland, possesses significant antioxidant activity. This study explores the therapeutic effect of melatonin on the deleterious effects of deltamethrin, a pyrethroid pesticide extensively used worldwide, including in Türkiye, on mouse liver cells. Methods Hepatocytes from Balb/C mice were isolated using a two-stage perfusion method, resulting in over 85% live hepatocytes. The isolated cells were cultured with different doses of deltamethrin (1 and 10 µM) and melatonin (100 µM) for 24 and 48 hours. At the conclusion of the culture period, hepatocytes were extracted at the 24th and 48th hours, and Malondialdehyde (MDA), Total Antioxidant Capacity (TAC), Total Oxidation Status (TOS), and DNA damages (8-hydroxy-2’-deoxyguanosine (8-OHdG)) were examined. Results While an increase in MDA, TOS, and DNA damage was observed in the deltamethrin-administered groups of hepatocytes, a decrease in TAC level was noted. It was determined that the applied deltamethrin had no effect on cell viability throughout the application period. Conclusion Furthermore, it was observed that melatonin, when administered concurrently with deltamethrin, reduced the toxic effect of deltamethrin. This study suggests that melatonin has a protective effect against deltamethrin-induced damage in mouse hepatocyte cells.

Efficacy of colchicine and melatonin in the treatment of rat endometriosis model: An animal study

ObjectiveThis study investigates the therapeutic effects of colchicine and melatonin on endometriotic implants in an experimentally created endometriosis model in rats. Study designForty-four adult female Wistar albino rats weighing between 260 and 300 g, 8 weeks old, were selected for the study. The unilateral uterine horn of rats with a bicornuate uterus was excised for 1 cm, washed with sterile saline, incised longitudinally, and the endometrium was exposed. A 0.5*0.5 cm endometrial tissue sample taken with a scalpel was implanted with suturing (4/0 Vicryl) to the abdominal wall. Forty-four rats were divided into four groups. Group 1 was randomized as the endometriosis group (control), Group 2 as endometriosis + colchicine treatment, Group 3 as endometriosis + melatonin treatment, and Group 4 as the endometriosis + melatonin + colchicine treatment group. The colchicine (Sigma Chemical Co., St Louis, Missouri) group was administered orally at a dose of 0.1 mg/kg, and the Melatonin group orally at a dose of melatonin (20 mg/kg per day). Treatment continued daily for 30 days. ResultsIn the post-treatment focal diameter measurements, the endometrial focal diameter in the colchicine and colchicine + melatonin group was significantly lower than the control group (p=0.026). Bcl-2 levels of the colchicine group were lower than the control group and the melatonin group (p=0.021). ConclusionColchicine and melatonin reduce adhesion to the peritoneal surface in ectopic endometrial cells. It also acts by increasing apoptosis and decreasing cell survival.

An optofluidic system for the concentration gradient screening of oocyte protection drugs

Oocytes protective drug screening is essential for the treatment of reproductive diseases. However, few studies construct the oocyte in vitro drug screening microfluidic systems because of their enormous size, scarcity, and sensitivity to the culture environment. Here, we present an optofluidic system for oocyte drug screening and state analysis. The system consists of two parts: an open-top drug screening microfluidic chip and an optical Fourier filter analysis part. The open-top microfluidic chip anchors single oocyte with hydrogel and allows nutrient and gas environment updating which is essential for oocyte culturing. The optical filter analysis part is used to accurately analyse the status of oocytes. Based on this system, we found that fluorene-9-bisphenol (BHPF) damaged the oocyte spindle in a dose-dependent manner, a high dose of melatonin (10−3 M) effectively reduces the percentage of abnormally arranged chromosomes of oocytes exposed to 40 μM BHPF. This optofluidic system shows great promise for the culture of oocytes and demonstrates the robust ability for convenient multi-concentration oocytes drug screening. This technology may benefit further biomedicine and reproductive toxicology applications in the lab on a chip community.

Preclinical Effects Of Melatonin On The Development Of Ehrlich's Tumor: A Biochemical, Cognitive, And Molecular Approach.

It has already been shown that melatonin is an antitumoral molecule that affects malignant cells via some mechanisms. The benefit played by this hormone on cancer is due to its antioxidant effects. This study aimed to evaluate the preclinical effects of melatonin in mice with the Ehrlich ascites tumor. Twenty Balb/ c male mice with Ehrlich tumor were treated with different melatonin doses. Their inflammatory and oxidative stress were accessed by gene expression. Hepatotoxicity and hematological parameters were also evaluated through biochemical analyses. Animal welfare was analysed weekly from the categories guided by the NC3Rs. Gene expression analyses have shown that only Tnfα and Sod1 were expressed in all groups studied. Only the M-3 group showed increased Tnfα expression compared to the control. All groups treated with melatonin showed decreased Sod1 expression compared to the control. No signs of hepatotoxicity were caused by any of the melatonin doses used in the treatment. In animals with Ehrlich´s tumor treated with melatonin, a decrease in oxidative stress, an amelioration in welfare and in cognitive tasks could be observed, even if the treatment has not reduced the size of the tumor itself. In parallel with the already patented use of melatonin in the treatment of sleep disorders or chronic kidney disease, our results propose its use to improve the general well-being of breast cancer patients.

Melatonin Promotes Differentiation of Human Spermatogonial Stem Cells Cultured on Three-Dimensional Decellularized Human Testis Matrix.

The use of 3D (3-Dimensional) culture systems supported cell-to-cell and cell-to-extracellular matrix (ECM) interactions, proliferation, and differentiation of SSCs (Spermatogonial stem cells). The potential advantages of ECM-based scaffolds for in vitro spermatogenesis have been indicated in human and animal experiments. Furthermore, the strong antioxidant and anti-inflammatory activities of melatonin have improved in vitro manipulation of human SSCs in culture conditions. SSCs were isolated from the testis of three dead-brain patients and then propagated for four weeks. The characterization of SSC colonies was done using real-time PCR (Polymerase chain reaction), ICC (Immunocytochemistry), and xenotransplantation to mice model. Decellularization of the human testis was performed using 0.3% sodium dodecyl sulfate (SDS) solution and 1% Triton X-100. Also, various characterizations of DTM (Decellularized testicular matrix ) were carried out using histological staining and DNA content analysis. The optimum dose of melatonin was selected by MTT (Methyl thiazol tetrazolium). SSCs were cultured in 4 groups: control, melatonin, ECM, and ECM-melatonin in a differentiation medium for four weeks. The expression of differentiation genes was evaluated by real-time polymerase chain reaction. In addition, the viability of cultured cells was assessed by MTT assay. The results of ICC and real-time PCR showed the expression of undifferentiated SSC markers (PLZF and GRFA1) in SSC colonies following the 2D culture of isolated SSCs. The presence of testicular ECM components after different staining methods; and the reduction of DNA content confirmed the proper decellularization process. Germ cell apoptosis significantly decreased in melatonin and ECM groups, and the higher viability of SSCs was seen in the ECM-melatonin group. The relative expression of GFRA1 and PRM2 decreased and increased in ECM and ECM-melatonin groups, respectively. Our study showed that the addition of melatonin to the human naturally-derived ECM scaffold could provide a suitable platform for inducing the differentiation and preserving the viability of SSCs.

Melatonin in energy control: Circadian time-giver and homeostatic monitor.

Melatonin is a neurohormone synthesized from dietary tryptophan in various organs, including the pineal gland and the retina. In the pineal gland, melatonin is produced at night under the control of the master clock located in the suprachiasmatic nuclei of the hypothalamus. Under physiological conditions, the pineal gland seems to constitute the unique source of circulating melatonin. Melatonin is involved in cellular metabolism in different ways. First, the circadian rhythm of melatonin helps the maintenance of proper internal timing, the disruption of which has deleterious effects on metabolic health. Second, melatonin modulates lipid metabolism, notably through diminished lipogenesis, and it has an antidiabetic effect, at least in several animal models. Third, pharmacological doses of melatonin have antioxidative, free radical-scavenging, and anti-inflammatory properties in various in vitro cellular models. As a result, melatonin can be considered both a circadian time-giver and a homeostatic monitor of cellular metabolism, via multiple mechanisms of action that are not all fully characterized. Aging, circadian disruption, and artificial light at night are conditions combining increased metabolic risks with diminished circulating levels of melatonin. Accordingly, melatonin supplementation could be of potential therapeutic value in the treatment or prevention of metabolic disorders. More clinical trials in controlled conditions are needed, notably taking greater account of circadian rhythmicity.

Exploring the potential use of melatonin as a modulator of tramadol-induced rewarding effects in rats.

Melatonin is responsible for regulating the sleep-wake cycle and circadian rhythms in mammals. Tramadol, a synthetic opioid analgesic, is used to manage moderate to severe pain but has a high potential for abuse and dependence. Studies have shown that melatonin could be a potential modulator to reduce tramadol addiction. Male Wistar rats were used to investigate the effect of melatonin on tramadol-induced place preference. The rats were divided into four groups: control, tramadol, tramadol + melatonin (single dose), and tramadol + melatonin (repeated doses). Tramadol was administered intraperitoneally at 40mg/kg, while melatonin was administered at 50mg/kg for both the single dose and repeated-dose groups. The study consisted of two phases: habituation and acquisition. Tramadol administration produced conditioned place preference (CPP) in rats, indicating rewarding effects. However, melatonin administration blocked tramadol-induced CPP. Surprisingly, repeated doses of melatonin were ineffective and did not reduce the expression of CPP compared to that of the single dose administration. The study suggests that melatonin may be a potential therapeutic option for treating tramadol addiction. The results indicate that melatonin attenuates the expression of tramadol-induced CPP, supporting its uses as an adjunct therapy for managing tramadol addiction. However, further studies are needed to investigate its effectiveness in humans.

Simulated pharmacokinetics of inhaled caffeine and melatonin from existing products indicate the lack of dosimetric considerations

Numerous commercially available inhalable products claim to improve sleep-wake cycle-related target indications by delivering a wide variety of chemicals like caffeine and melatonin. The resulting exposure-responses from inhaling different doses are unknown and obtaining early understanding of resulting pharmacokinetics is beneficial. This study applied a physiologically based pharmacokinetic modeling approach to predict the inhalation pharmacokinetics of caffeine and melatonin for different target indications related to the sleep-wake cycle. The model predicted rapid systemic delivery of caffeine and melatonin based on airway regional deposition of inhaled aerosol. A low inhaled dose of 1 mg of caffeine resulted in a 72.3-times lower plasma maximal concentration and was predicted to not improve cognitive performance task outcomes compared to oral consumption of coffee containing 80 mg of caffeine. Conversely, 2-mg oral and inhaled doses of melatonin under recommended directions of use result in more than 25.1- and 645-times higher plasma concentrations compared to endogenous melatonin, respectively. The recommended doses for inhalation products for potential improvement in the target indications vary widely. Additional research is needed to evaluate the human pharmacokinetics, efficacy, and safety of inhaled products. Given the lack of assessments, inhaled caffeine and melatonin must be consumed with caution as the toxicological concerns are not known and could outweigh the potential beneficial effects.

The Effects of Pre-Harvest Melatonin Applications on Phytochemical Properties of Crimson Seedless Grape Variety (V. vinifera L.)

Foliar melatonin applications are crucial for grape quality as they can enhance skin color development, increase antioxidant capacity and nutritional value of grapes. The effectiveness of preharvest melatonin applications may change depending on fruit species, variety, application time, and dose. In the current study, it was utilized from various doses of melatonin application, including 0, 0.25, 0.50, and 1 mmol l-1 for improving the phytochemical attributes of Crimson Seedless table grape variety. The results of the principal component analysis showed that different doses of foliar melatonin application had different effects on the yield and biochemical attributes of grape variety. But particularly, 1 mmol l-1 and 0.50 mmol l-1 of melatonin doses had significant effects on total phenolic compounds content and antioxidant capacity from the phytochemical properties of Crimson Seedless table grape variety.

Do exogenous melatonin and nitric oxide mitigate the adverse effects of flooding stress in spinach?

Studies are being conducted to develop strategies to reduce the adverse effects of flooding stress in plants, including melatonin and nitric oxide (NO) applications. In the present study, we tried six different application subjects: full irrigation - control (FI), flooding stress (FS), FS + application of 50 µM melatonin, FS + application of 100 µM melatonin, FS + application of 50 µM nitric oxide (NO), and FS + application of 100 µM NO. The flooding subjects were subjected to stress 10 days before harvest, which was continued until harvest. Melatonin and nitric oxide were applied to plant leaves twice, with a 1-week interval, by spraying to cover the whole plant. We found that flooding stress reduced in certain agronomic parameters and exerted a negative effect on leaf relative water content (RWC), chlorophyll a, b, carotenoid, and protein content, actual photosynthetic efficiency (PSII), stomatal conductance (gs), and chlorophyll fluorescence (Fv/Fm). In addition to increasing the reactive oxygen species (ROS) production under stress conditions, Flooding stress significantly increased the content of proline, leaf temperature, and antioxidant enzyme activity. The melatonin and nitric oxide doses contributed to plant development as well as regulated the pigment content, thereby promoting the ROS-scavenging antioxidant defense system. The principal component analysis (PCA) performed to evaluate the data collectively revealed that full irrigation yielded the best results for agronomic and physiological parameters. The PCA results demonstrated that FS + application of 100 µM melatonin, located in the region closest to full irrigation conditions, was the most effective application under flooding stress conditions. Melatonin applications are crucial for sustainable agriculture, thereby reducing the yield and quality losses compared to nitric oxide applications in regions where spinach is cultivated, and there is a risk of floods.