Humans ; Myocardial Reperfusion Injury/prevention & control* ; Melatonin/therapeutic use* ; Mitochondria ; Myocardial Infarction

Neonatal hypoxic-ischemic encephalopathy (HIE) remains one of the leading causes of death and long-term neurodevelopmental disorders in full-term neonates, and there is currently no curative treatment. Therapeutic hypothermia is now a standard therapy for HIE in the neonatal intensive care unit, but its safety and efficacy in remote areas remains unclear. Melatonin is an indole endocrine hormone mainly produced by the pineal gland and it has the ability to easily penetrate the blood-brain barrier. Through receptor and non-receptor mechanisms, melatonin exerts anti-oxidative and anti-inflammatory effects and participates in the regulation of organelle function and the inhibition of cell death. Melatonin is considered one of the most promising drugs for the treatment of HIE based on its reliable safety profile and clinical/preclinical results. This article reviews the recent research on the use of melatonin in combination with therapeutic hypothermia for the treatment of neonatal HIE.
Infant, Newborn ; Humans ; Melatonin/therapeutic use* ; Hypoxia-Ischemia, Brain/therapy* ; Hypothermia, Induced ; Intensive Care Units, Neonatal

OBJECTIVETo study serum levels of melatonin in children with epilepsy or febrile seizures in order to provide a basis for the treatment of epilepsy or febrile seizures with melatonin.

METHODSSerum melatonin levels were measured using ELISA in 15 children with simple febrile seizure (SFS), in 15 children with complex febrile seizure (CFS), in 15 children with epilepsy, and in 15 children with upper respiratory infections (control group).

RESULTSSerum melatonin levels in children with epilepsy (8.66+/-1.38 ng/L) or CFS (14.91+/-2.61 ng/L) were significant lower than those in the control group (23.93+/-2.01 ng/L) (P<0.01). The SFS group showed lower serum melatonin levels (20.72+/-2.54 ng/L) compared with the control group, but there were no statistical differences between the two groups. Serum melatonin levels in the epilepsy group were significantly lower than those in the CFS (P<0.05) and the SFS groups (P<0.01).

CONCLUSIONSSerum melatonin levels decreased in children with epilepsy or CFS. Supplement of exogenous melatonin might be a promising treatment for epilepsy and febrile seizures in children.

Child ; Child, Preschool ; Epilepsy ; blood ; drug therapy ; Female ; Humans ; Infant ; Male ; Melatonin ; blood ; pharmacology ; therapeutic use ; Seizures, Febrile ; blood

OBJECTIVETo investigate the protective effect of melatonin on residual hair follicle cells of scald rats at early stage.

METHODSEighteen male Sprague-Dawley rats were randomly divided into scald group, treatment group, sham group , with 6 rats in each group. The rats in scald group and treatment group were subjected to 30% TBSA partial thickness scald on the back, and were resuscitated with balanced solution after 1 hour, while those in sham group were immersed in water at 37 degrees C for 25 s to simulate scald, and did not receive fluid replacement. Rats in treatment group were intraperitoneally injected with 10 mg/kg melatonin solution at 1 minute, 8 hours and 12 hours after scald, while those in sham group and scald group were given equal volume of 1% alcohol sodium-isotonic saline instead. Tissue samples were harvested at 6, 12 and 24 post scald hours (PSH) for determination of MDA and GSH levels. Apoptosis of residul hair follicle was detected by TUNEL method and immunohistochemistry of caspase-3.

RESULTSThe level of MDA in scald group at each time point was much higher than that in sham group (P < 0.01) and treatment group (P < 0.05), and it peaked at 12 PSH. The changes in GSH were just opposite to that of MDA. Under fluorescence microscope, the residual hair follicle cells were blue, and the apoptotic cells appeared green. The apoptosis rate in scald group at 6, 12, 24 PSH was obviously higher than that in sham (P < 0.01) and treatment groups (P < 0.05), which was (20.2 +/- 3.4)% vs (4.3 +/- 2.3)% vs (10.9 +/- 3.2)%, (31.2 +/- 3.6)% vs (5.1 +/- 2.5)% vs (19.1 +/- 3.7)%, (22.4 +/- 2.7)% vs (4.1 +/- 2.4)% vs (13.1 +/- 3.4)%, respectively. The score of caspase-3 positive cell in scald group was higher than those in sham group (P < 0.01) and treatment group (P < 0.05).

CONCLUSIONSThere is obvious correlation between oxidative stress and apoptosis rate of hair follicle cells in rats with partial thickness scald. Early administration of melatonin may have anti-apoptosis ability for residual hair follicle cells by attenuation of oxidative stress.

Animals ; Apoptosis ; Burns ; drug therapy ; metabolism ; Hair Follicle ; cytology ; metabolism ; Male ; Melatonin ; therapeutic use ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley

PURPOSE: Postoperative intraabdominal adhesion formation is a major clinical problem. No previous study was found, reporting the relationship between adhesion formation and melatonin administration, but melatonin, a strong antioxidant, is recognized to have certain effects on the progression of adhesion formation mechanism. It was therefore decided to investigate the effects of melatonin on postoperative adhesion formation. MATERIALS AMD METHODS: A total number of 24 Spraque-Dawley rats were utilized. Three groups, described as: Group A, sham laparatomy (n=8), Group B, rats that underwent only ischemia-reperfusion (n=8) and Group C, rats that underwent ischemia- reperfusion and were given 10 mg/kg melatonin solution i.v. (n=8). For Groups B and C, the ileocolic vessels were clamped. Blood glutathione peroxidase levels of all study groups were assessed, then microscopic and macroscopic adhesion scores were evaluated. RESULTS: Glutathione peroxidase levels of the melatonin-treated group were significantly higher and fibroblast proliferation and macroscopic adhesion scores were significantly lower, than in the melatonin-free group. CONCLUSION: The results of this study supported the hypothesis, that melatonin administration may prevent intraabdominal adhesions resulting from surgery.
Abdomen/pathology/*surgery ; Animals ; Antioxidants/*therapeutic use ; Melatonin/*therapeutic use ; Postoperative Complications/*prevention & control ; Rats ; Rats, Sprague-Dawley ; Tissue Adhesions/drug therapy/pathology

BACKGROUNDOur earlier studies indicate that melatonin inhibits the proliferation of prolactinoma and induces apoptosis of pituitary prolactin-secreting tumor in rats. Melatonin has also been shown to induce apoptosis and to reduce the production of ATP in breast tumor cells. This study analyzed the levels of the four mitochondrial respiratory complexes and the production of ATP and also the effects of melatonin treatment of prolactinoma.

METHODSIn the in vivo study, mitochondria were harvested from control pituitaries or prolactinoma collected from the pituitaries of melatonin- and 17-β-estradiol (E2)-treated male rats. In the in vitro study, prolactinoma cells mitochondria were harvested. Activities of the four mitochondrial respiratory complexes were assayed using fluorometer. ATP production of prolactinoma cells was estimated using bioluminescent methods.

RESULTSElevated levels of four mitochondrial respiratory complexes activities and ATP production were recorded in prolactinoma cells. Moreover, in both in vivo and in vitro studies, melatonin inhibited the activities of mitochondrial respiratory complexes and the production of ATP in prolactinoma cells.

CONCLUSIONSThere is a link between mitochondrial function increase and tumorigenesis. Melatonin induces apoptosis of pituitary prolactin-secreting tumor of rats via the induction of mitochondrial dysfunction and inhibition of energy metabolism.

Adenosine Triphosphate ; metabolism ; Animals ; Estradiol ; therapeutic use ; Male ; Melatonin ; therapeutic use ; Mitochondria ; drug effects ; metabolism ; Prolactin ; metabolism ; Prolactinoma ; drug therapy ; metabolism ; Rats ; Rats, Sprague-Dawley

BACKGROUNDThe iron catalyzed lipid peroxidation plays an important role in the autodestruction of the injured spinal cord. This study was to detect the antioxidation of melatonin against spinal cord injury (SCI) in rats.

METHODSSity Sprague-Dawley rats were randomly divided into four groups: group A (n = 15) for laminectomyanly, group B (n = 15) for laminectomy with SCI, group C (n = 15) for SCI and intraperitoneal injection of a bolus of 100 mg/kg melatonin, and group D (n = 15) for SCI and intraperitoneal injection of saline containing 5% ethanol. The SCI of animal model was made using modified Allen's method on T12. Six rats of each group were sacrificed 4 hours after injury, and the levels of free iron and malondialdehyde (MDA) of the involved spinal cord segments were measured by the bleomycin assay and thiobarbituric acid (TBA) separately. Functional recovery of the spinal cord was assessed by Modified Tarlov's scale and the inclined plane method at 1, 3, 7, 14, 21 days after SCI. The histologic changes of the damaged spinal cord were also examined at 7 days after SCI.

RESULTSAfter SCI, the levels of free iron and MDA were increased significantly and the modified Tarlov's score and inclined plane angle decreased significantly in groups B and D. In group C, the Tarlov's score and inclined plane angle were increased significantly at 7, 14 and 21 days, with histological improvement.

CONCLUSIONMelatonin can reduce the level of lipid peroxidation and prevent damage to the spinal cord of rat.

Animals ; Antioxidants ; therapeutic use ; Iron ; analysis ; Lipid Peroxidation ; drug effects ; Male ; Malondialdehyde ; analysis ; Melatonin ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Spinal Cord Injuries ; drug therapy ; metabolism ; pathology

AIM: Stress is recognized to precipitate anxiety and related psychological problems characterized by a wide range of biochemical and behavioral changes. The present study was carried out to investigate the protective effects of melatonin and buspirone, and their combination, against six hours immobilization stress-induced, anxiety-like behavioral and oxidative damage in mice. METHOD: Male Laca mice were pre-treated with melatonin (2.5, 5 mg·kg(-1)), buspirone (5, 10 mg·kg(-1)), and their combination for consecutive five days. On the 6(th) day, animals were immobilized for six hours, and thereafter various behavioral tests were performed followed by biochemical tests. RESULTS: Immobilization stress significantly impaired body weight, locomotor activity, and caused anxiety-like behavior, along with increased oxidative damage. Pretreatment with melatonin and buspirone significantly improved the loss in body weight and locomotor activity, attenuated anxiety-like behavior (in both the mirror chamber and plus maze performance tasks), further restored the levels of brain total proteins, and caused antioxidant-like effects, as evidenced by reduced lipid peroxidation, nitrite concentration, and restoration of reduced glutathione and catalase activity, as compared to control animals. In addition, combination of melatonin (2.5, 5 mg·kg(-1)) with buspirone (5 mg·kg(-1)) significantly potentiated their protective effects, as compared to their effects individually. CONCLUSION The present study suggests that melatonin potentiates the beneficial effect of buspirone against immobilization stress-induced, anxiety-like behavioral and oxidative damage in mice possibly by involving a serotonergic mechanism.
Animals ; Anti-Anxiety Agents ; pharmacology ; therapeutic use ; Antioxidants ; pharmacology ; therapeutic use ; Anxiety ; drug therapy ; Behavior, Animal ; drug effects ; Buspirone ; pharmacology ; therapeutic use ; Immobilization ; psychology ; Male ; Melatonin ; pharmacology ; therapeutic use ; Mice, Inbred Strains ; Oxidative Stress ; drug effects ; Stress, Psychological ; drug therapy

OBJECTIVES: To study the protective effect of melatonin (Mel) against oxygen-induced retinopathy (OIR) in neonatal mice and the role of the HMGB1/NF-κB/NLRP3 axis. METHODS: Neonatal C57BL/6J mice, aged 7 days, were randomly divided into a control group, a model group (OIR group), and a Mel treatment group (OIR+Mel group), with 9 mice in each group. The hyperoxia induction method was used to establish a model of OIR. Hematoxylin and eosin staining and retinal flat-mount preparation were used to observe retinal structure and neovascularization. Immunofluorescent staining was used to measure the expression of proteins and inflammatory factors associated with the HMGB1/NF-κB/NLRP3 axis and lymphocyte antigen 6G. Colorimetry was used to measure the activity of myeloperoxidase. RESULTS: The OIR group had destruction of retinal structure with a large perfusion-free area and neovascularization, while the OIR+Mel group had improvement in destruction of retinal structure with reductions in neovascularization and perfusion-free area. Compared with the control group, the OIR group had significant increases in the expression of proteins and inflammatory factors associated with the HMGB1/NF-κB/NLRP3 axis, the expression of lymphocyte antigen 6G, and the activity of myeloperoxidase (P<0.05). Compared with the OIR group, the OIR+Mel group had significant reductions in the above indices (P<0.05). Compared with the control group, the OIR group had significant reductions in the expression of melatonin receptors in the retina (P<0.05). Compared with the OIR group, the OIR+Mel group had significant increases in the expression of melatonin receptors (P<0.05). CONCLUSIONS Mel can alleviate OIR-induced retinal damage in neonatal mice by inhibiting the HMGB1/NF-κB/NLRP3 axis and may exert an effect through the melatonin receptor pathway.
Animals ; Mice ; HMGB1 Protein ; Melatonin/therapeutic use* ; Mice, Inbred C57BL ; NF-kappa B ; NLR Family, Pyrin Domain-Containing 3 Protein ; Oxygen/adverse effects* ; Peroxidase ; Receptors, Melatonin ; Retinal Diseases/drug therapy*

AIMTo observe the effect of melatonin (MT) on morphine withdrawal syndromes and determine the content of NO in plasma and brain tissue in morphine dependent mice.

METHODSA physical dependent model in mice was established by subcutaneous injection of morphine. MT (15 mg.kg-1, qd x 3) was given by intragastric infusion (ig) for three days. Withdrawal syndromes were induced by intraperitoneal injection of naloxon (5 mg.kg-1). The intensity of withdrawal syndromes was evaluated according to the jumping latency, the jumping times and the body weight loss. The content of NO was detected with Griess method.

RESULTSThe jumping latency of morphine withdrawal reaction was prolonged and the jumping times were reduced obviously by ig MT. The increased NO content in plasma and brain tissue in morphine dependent mice was reduced by ig MT.

CONCLUSIONThe physical withdrawal syndromes and the content of NO in plasma and brain tissue in morphine dependent mice are inhibited by MT.

Animals ; Brain ; drug effects ; metabolism ; Disease Models, Animal ; Male ; Melatonin ; therapeutic use ; Mice ; Morphine Dependence ; blood ; Nitric Oxide ; blood ; Substance Withdrawal Syndrome ; blood ; prevention & control