Search NEL Online

Journal Article 2006; 27(5): 601-608 PubMed PMID: 17186997 Citation  Keywords:  Animals, Azo Compounds:pharmacology, Dose-Response Relationship, Drug, Fibroblasts:drug effects, Lipid Metabolism:drug effects, Melatonin:pharmacology, Mice, NIH 3T3 Cells, Oleic Acid:pharmacology, Receptors, Melatonin:antagonists & inhibitors, Tryptamine.   

: The current study was undertaken to uncover the role of melatonin in lipid metabolism in the murine fibroblasts. The results show melatonin in vitro enhances lipid accumulation and lipid droplet formation in this cell line. Using oil red O staining, it was found that when oleic acid was present in the culture media, melatonin at doses of 0.1-2mM, significantly increased the lipid concentrations in the cells. However, low levels of melatonin, with or without oleic acid, did not influence lipid metabolism in the cultured fibroblasts. When a non-specific melatonin receptor antagonist, luzindole 10 microM was co-incubated with 1mM melatonin, the stimulatory effects of melatonin on lipid accumulation in these cells was significantly reduced. It appears that the effects of melatonin on lipid metabolism in murine fibroblasts is mediated by melatonin membrane receptors....

Read abstract  Full text PDF

Comparative Study 2006; 27(5): 623-630 PubMed PMID: 17159820 Citation  Keywords:  Adenine Nucleotides:analysis, Adenosine Triphosphatases:metabolism, Adenosine Triphosphate:biosynthesis, Animals, Diaphragm:drug effects, Melatonin:pharmacology, Mice, Mice, Inbred C57BL, Mice, Knockout, Mitochondria, Muscle:chemistry, Muscle, Skeletal:ch.   

OBJECTIVES: To evaluate the changes in the mitochondrial ATP production during sepsis and the participation of iNOS in these changes. We also assessed the effect of melatonin administration in this experimental paradigm.

METHODS: The activity of ATPase, the level of adenine nucleotides, and the ATP production were measured in mitochondria of diaphragm and hind leg skeletal muscle of wild type (iNOS+/+) and knockout iNOS (iNOS-/-) mice. Three experimental groups were done: control group; group of septic mice induced by cecal ligation and puncture (CLP), and group of septic mice treated with melatonin. Mice were killed 24 hours after CLP. Melatonin was administrated in four doses (30 mg/kg b.w.) as follows: 30 min before CLP (i.p.) and 30 min, 4 h and 8 h after CLP (s.c.).

RESULTS: Mitochondrial production of ATP decreased in iNOS+/+ but not in iNOS-/- mice after sepsis. No changes in the ATPase activity were found in any group. Melatonin treatment normalized the production of ATP in iNOS+/+ mice, without affecting iNOS-/- animals.

CONCLUSIONS: The reduction of the ATP production in iNOS+/+ but not in iNOS-/- mice suggest the participation of iNOS in the impairment of mitochondrial function in the former. Because ATPase was unaffected by sepsis, it is suggested the ATP deficit depended on the sepsis-induced respiratory chain damage. The normalization of the production of ATP with melatonin may explain the reduction of the mortality reported elsewhere in experimental and clinical sepsis after treatment with the indoleamine....

Read abstract  Full text PDF

Journal Article 2006; 27(1-2): 81-84 PubMed PMID: 16648798 Citation  Keywords:  Aflatoxin B1:antagonists & inhibitors, Animals, Antioxidants:pharmacology, Apoptosis:drug effects, Cell Death:drug effects, Injections, Intraperitoneal, Male, Melatonin:pharmacology, Rats, Rats, Wistar, Thyroid Gland:cytology,.   

OBJECTIVES: Apoptosis, or programmed cell death, is a normal component in the development of multicellular organisms and is essential for many physiological processes. Apoptosis is a process in which cells play an active role in their own death (apoptosis is often referred to as "cell suicide"). Disturbances of apoptosis regulation can result in many diseases. Certain substances (for example--aflatoxin B1; AFB1) can induce apoptosis in various organs and tissues. Melatonin (Mel) is a hormone (indoleamine) which has antioxidant, antiproliferative and, potentially, anticancerogenic activities. The aim of our study was to examine the influence of late-afternoon (1600-1800) intraperitoneal (i.p.) Mel injections, administered for 3 weeks, on the process of apoptosis in male Wistar rat thyroid follicular cells (TFC); Mel was injected alone or together with AFB1 (i.p., also once daily for 3 weeks).

METHODS: In order to assess the process of apoptosis, evaluated in microscopic preparations of rat thyroids, an In Situ Cell Death Detection, POD Kit [Roche, GER] and the DAKO Liquid DAB Substrate-Chromogen System [DakoCytomation, USA] were employed.

RESULTS: Aflatoxin B1 increased the apoptotic index (I(apopt)) in rat TFC, in comparison to controls (p<0.001). The I(apopt) value in the rats, receiving Mel and AFB1 injections, was statistically lower, as compared to the value of the examined index in the group of AFB1-treated animals (p<0.001). No statistically significant differences of I(apopt) value were observed between the Mel-treated group of animals and the controls.

CONCLUSION: Melatonin can assumingly regulate the growth of cells and tissues by influencing the process of apoptosis....

Read abstract

Journal Article 2006; 27(1-2): 263-266 PubMed PMID: 16648794 Citation  Keywords:  Animals, Injections, Intraperitoneal, Lactic Acid:blood, Male, Melatonin:pharmacology, Rats, Rats, Sprague-Dawley, Swimming:psychology, Zinc:blood,.   

OBJECTIVE: The objective of the present study is to examine the effect on melatonin supplementation on plasma lactate levels and its relation with zinc in rats subjected to acute swimming exercise.

METHODS: Thirty adult male rats of Spraque-Dawley species were allocated to 3 groups, each containing an equal number of rats: general control group which was not subjected to any procedure (Group 1), the group which was subjected to 30 minutes acute swimming exercise (Group 2), and the group which was subjected to 30 minutes acute swimming exercise after 4-week intraperitoneal (i.p.) melatonin (3 mg/kg/day) supplementation. Lactate and zinc levels in the plasma were studied in the blood samples taken from the experimental animals by decapitation method.

RESULTS: The animals in the control group, which was not subjected to any procedure (group 1), had higher lactate levels than those in groups 2 and 3 (p<0,05). Lactate levels in the swimming group supplemented with melatonin (group 3) were lower than those in group 2 (swimming group) (p<0,05). The highest plasma zinc levels were obtained in the melatonin-supplemented swimming group (group 3) (p<0,05). Group 2 (swimming control) had the lowest plasma zinc levels (p<0,05).

CONCLUSION: Results of the study demonstrate that melatonin supplementation to rats subjected to acute swimming exercise reduces lactate levels, thereby delaying exhaustion. Increased zinc levels may be mediating this melatonin effect....

Read abstract

Journal Article 2003; 24(5): 350-354 PubMed PMID: 14647012 Citation  Keywords:  Animals, Anti-Bacterial Agents:pharmacology, Antioxidants:pharmacology, Female, Graft Survival, Malondialdehyde:blood, Melatonin:pharmacology, Necrosis, Ovary:metabolism, Oxytetracycline:pharmacology, Peritoneal Cavity, Rats, Rats, Wistar,.   

OBJECTIVES: To comparatively investigate the effects melatonin and oxytetracycline as antioxidants on autologous intraperitoneal ovary transplantation in rats.

SETTING AND DESIGN: 28 adult female Wistar rats with regular estrous cycles were randomly divided into four groups. Group 1 (n=7) was the control group; Group 2 (n=7) bilateral oophorectomy and intraperitoneal transplantation group; and Groups 3 (n=7) and 4 (n=7) firstly received 20 mg/kg/IP melatonin and 10 mg/kg/IP oxytetracycline., respectively and fifteen minutes after that, they had bilateral oophorectomy and intraperitoneal transplantation. Ovarian tissue and blood malondialdehyde (MDA) levels, superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) levels were determined. Vaginal cytology and ovarian necrosis were histopathologically investigated. Kruskall Wallis analysis of variance was used in the statistical analysis of data.

RESULTS: Ovarian necrosis, tissue MDA and plasma MDA levels were significantly higher in Group 2 compared to the Groups 1, 3 and 4 (p<0.03). SOD and GSHPx levels were significantly lower in group 2 compared to the groups 1, 3 and 4 (p<0.03). Melatonin was found to be more effective on ovarian necrosis and tissue MDA level than the use of oxytetracycline following autologous intraperitoneal ovary transplantation (p<0.03). There was a significant positive correlation between tissue MDA level and ovarian necrosis and a very strong negative correlation between tissue MDA and SOD level (rs = +/-0.9, n=28, p=0.000).

CONCLUSION: Although both melatonin and oxytetracycline were found to be effective in autologous intraperitoneal pelvic ovary transplantation, melatonin is more effective against both the ovarian necrosis and tissue MDA level in rats....

Read abstract

Journal Article 2003; 24(5): 345-347 PubMed PMID: 14647010 Citation  Keywords:  Animals, Antioxidants:pharmacology, Hyperthyroidism:drug therapy, Injections, Intraperitoneal, Male, Melatonin:pharmacology, Rats, Rats, Sprague-Dawley, Testis:drug effects, Testosterone:metabolism, Thyroid Gland:drug effects, Thyroid Hormones:metabolism,.   

OBJECTIVE: Melatonin has a general inhibitory effect on the reproductive system and thyroid functions. Testosterone secretion increases in parallel to thyroid hormones in hyperthyroidism. The aim of this study was to investigate the effects of melatonin application on total T3, T4 and testosterone in hyperthyroid rats.

METHODS: This study was performed on 4 groups each consisted of 6 male Spraque Dawley rats. Control group (G1); sham group (G2); applied 0.5 ml/day of serum physiologic intraperitoneally for 2 weeks, hyperthyroid group (G3); applied 0.3 mg/kg/day thyroxine intraperitoneally for 2 weeks, and hyperthyroid and melatonin supplemented group (G4); applied 0.3 mg/kg/day thyroxine and 3 mg/kg/day melatonin. Blood samples taken by way of decapitation were analysed for total T3, T4 and testosterone by RIA.

RESULTS: Serum total T3 and total testosterone levels were the highest in hyperthyroid group (G3), whereas in hyperthyroid and melatonin supplemented group (G4) were the lowest (P<0.001). Total T4 levels were higher in group 3 than group 1, 2 and 4 (P<0.001).

CONCLUSION: Results revealed that melatonin supplementation in hyperthyroidism suppress secretion of thyroid hormones and testosterone secretion....

Read abstract

Journal Article 2003; 24(5): 341-344 PubMed PMID: 14647009 Citation  Keywords:  3-Hydroxybutyric Acid:metabolism, Animals, Antioxidants:pharmacology, In Vitro Techniques, Malates:metabolism, Male, Melatonin:pharmacology, Mitochondria, Liver:drug effects, Oxygen Consumption:drug effects, Rats, Rats, Wistar, Succinic Acid:metabolism,.   

OBJECTIVE: To examine the in vitro effect of melatonin on rat mitochondrial liver respiration.

METHODS: Oxygen consumption by liver mitochondria was measured polarographically in the presence of one of the following Krebs' cycle substrates: Lsuccinate, DL-3- beta-hydroxybutyrate or L-malate. Respiratory velocities at rest (state 4) and during rapid respiration in the presence of substrate and adenosine diphosphate (state 3) were measured in the presence of 10 (-9)-10(-3) M concentrations of melatonin.

RESULTS: In vitro melatonin (10(-7)-10(-3) M) reduced state 3 mitochondrial respiration. Basal, state 4 respiration was not affected by melatonin. Consequently, control respiratory index (i.e., the ratio of state 3 to state 4 respiration) was inhibited by melatonin with a threshold at 10(-7) M concentration.

CONCLUSION: The ability of melatonin to curtail acutely the stimulation of oxygen consumption in liver mitochondria may protect the mitochondria from excessive oxidative damage....

Read abstract

Journal Article 2003; 24(5): 310-313 PubMed PMID: 14647002 Citation  Keywords:  Animals, Antioxidants:pharmacology, Circadian Rhythm, Cyclin-Dependent Kinase Inhibitor p21, Cyclins:metabolism, Male, Melatonin:pharmacology, Rats, Rats, Wistar, Thyroid Gland:cytology,.   

OBJECTIVES: The cell-cycle (cc) is, in part, controlled by cyclin-dependent kinases (CDKs), which are activated after binding cyclins (positive regulators of cc). CDK inhibitors (CDKIs), such as p15, p16, p21, and p27, inhibit cyclin-CDK complex activity, and function as negative cell cycle regulators, blocking cell-cycle progression. The aim of our study was to examine the influence of late-afternoon (1600-1800) subcutaneous (s.c.) melatonin (Mel) injections, administered for 2 weeks, on the p21 expression in male Wistar rat thyroid follicular cells (TFC).

METHODS: In order to detect the anti-p21 antibodies, the DAKO LSAB2 Rat Kit/HRP (DAKO, USA) and DAKO Liquid DAB Substrate-Chromogen System (DAKO, USA) were employed.

RESULTS: No statistically significant changes of p21(LI) (p21 labelling index) values were observed in particular groups of the rats receiving Mel injections, in comparison to the controls. The statistical difference of p21(LI) values (p<0.03) was only observed between groups of rats, receiving Mel injections in the dose of 25 microg/daily and 100 microg/daily.

CONCLUSION: Melatonin - in the applied doses and in the experimental conditions without any factors revealing anti-DNA activity - did not change, in any statistical way, p21 expression in rat thyroid follicular cells, as compared to the control group....

Read abstract