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Comparative Study 2004; 25(4): 257-261 PubMed PMID: 15361813 Citation  Keywords:  Adrenergic beta-Agonists:pharmacology, Age Factors, Animals, Circadian Rhythm:drug effects, Isoproterenol:pharmacology, Male, Melatonin:biosynthesis, Organ Culture Techniques, Photoperiod, Pineal Gland:drug effects, Rats, Rats, Wistar, Time Factors,.   

OBJECTIVES: The purpose of this study was to investigate and compare the effects of the beta-adrenergic agonist, isoproterenol, on induced increase in melatonin production in the pineal gland of young and old rats, at different circadian stages.

MATERIALS AND METHODS: We report here the effects of 10(-6) M isoproterenol-stimulated melatonin production by perifused pineal glands obtained from young (55 day old) and old (21 month old) male Wistar rats acclimatised to light:dark cycles regimen of 12:12 for 3 weeks. Pineal glands were collected at different circadian stages: 3, 7, 11, 15, 19 and 23 hours after light onset (HALO), and perifused for 510 min.

RESULTS: The basal levels of melatonin production in the young rats were approximately twice greater than those of the old rats. Isoproterenol stimulated melatonin production in both young and old rat pineal glands, whatever the circadian stage. The intensity of the response to 10(-6) M isoproterenol infusion was greater in young than in old rat pineal glands (P<0.001), with a trend towards an increase during the light phase, at 7 HALO, in both young and old rat pineal glands, although this trend towards increased melatonin response did not reach statistical significance (P>0.05).

CONCLUSIONS: These results show that isoproterenol is able to stimulate both young and old rat pineal glands whatever the circadian stage. The magnitude of isoproterenol stimulation is greater in young than in old glands. Our results also suggest that the pineal gland response to isoproterenol is not dependent on circadian stage, at least, under our experimental conditions....

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Comparative Study 2004; 25(4): 252-256 PubMed PMID: 15361812 Citation  Keywords:  Analysis of Variance, Animals, Free Radicals:analysis, Hydroxyl Radical:blood, Male, Melatonin:physiology, Nitrogen Oxides:blood, Pain:metabolism, Rats, Rats, Wistar, Reactive Oxygen Species:analysis, Serum:chemistry, Singlet Oxygen:blood, Somatosensory C.   

: The concentrations of ROS were measured in samples of the sensorimotor brain cortex and in the rat blood. We measured the following parameters: The six lines spectra, nitroxide radical, free hydroxyl radical and singleton oxygen. Their concentration was measured under physiological conditions, after the nociceptive stimulation and after the application of melatonin, both in normal and stimulated animals. In the brain cortex only the singleton oxygen decreased after the nociceptive stimulation, whereas the nitroxide radicals and six lines spectra increased. The free hydroxyl radicals did not change significantly. In the blood serum the six lines spectra and nitroxide radical increased, the concentration of the free hydroxyl radicals did not change. Melatonin increased both the hydroxyl and nitroxide radicals. There was a non-significant decrease in the six lines spectra. The estimation of ROS can be used as a tool for detecting metabolic changes and the consequences of different environmental influences, in our case the influence of nociception and melatonin....

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Comparative Study 2004; 25(1-2): 115-118 PubMed PMID: 15159694 Citation  Keywords:  Animals, Atrophy:prevention & control, Male, Melatonin:physiology, Organ Size, Pineal Gland:physiology, Rats, Rats, Wistar, Thymus Gland:pathology,.   

OBJECTIVES: The purpose of this study was to investigate the effects of pinealectomy and pinealectomy plus melatonin administration on thymus weight and histology in adult Wistar-albino rats.

METHODS: The animals were divided into three groups. Group I and Group II were designated as control (sham-pinealectomized) and pinealectomized rats, respectively. They received 10% ethanol (0.1 ml per day s.c.) alone. The rats in Group III were pinealectomized and daily injected with melatonin (3 mg/kg/0.1 ml 10% ethanol per day s.c.) commencing on the day seven after surgical operation. Injections were applied for two months.

RESULTS: The thymus atrophied and its weight decreased after pinealectomy (p<0.001). The cortico-medullary boundary could not be distinguished and in the thymus induced a loss of lymphoid elements, increased number of phagocytic macrophages and enlarged blood vessels. Melatonin prevented the thymic involution.

CONCLUSIONS: These results suggest that pinealectomy decreases thymus weight and that long-term administration of melatonin restores thymus weight to normal levels....

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Journal Article 2004; 25(1-2): 94-101 PubMed PMID: 15159691 Citation  Keywords:  Adenocarcinoma:metabolism, Animals, Disease Models, Animal, Female, Light, Melatonin:physiology, Ovarian Neoplasms:metabolism, Photoperiod, Poultry Diseases:metabolism, Turkeys:metabolism,.   

OBJECTIVES: The effect of photoperiod or melatonin treatments on ovarian adenocarcinoma in turkey breeder hens (Meleagris gallopavo) was investigated to evaluate the usefulness of this animal as a model for studying ovarian cancer.

METHODS: In Experiment 1, photoperiod effects were tested by exposing turkeys with ovarian tumors to 8 wks of short days (8:16LD) followed by a 12 wk period of long days (16:8LD). In Experiment 2, exogenous melatonin was administered to turkeys during long day-induced development of ovarian tumors. In both experiments, the stage of tumor growth was scored weekly on a scale of 0 to 4.

RESULTS: It was clear that exposure to short days produced complete regression of tumors, with a mean time to score 0 of 4.4 wks. Following re-exposure to a long photoperiod, all of the same birds showed re-growth of the ovarian tumor with a mean time to first palpable detection of 5.4 wks. When melatonin was administered daily during the long photoperiod (Experiment 2), there was a significant delay in the re-growth of tumors.

CONCLUSION: It was clear from this study that the growth of solid ovarian tumors in the turkey breeder hen was promoted by long photoperiods and ceased, to the point of remission, on short photoperiods. Thus, ovarian adenocarcinoma in turkeys can be completely manipulated by photoperiod. In addition, treatment with melatonin attenuates tumor growth in the turkey hen. The results suggest that the domestic turkey hen is a useful in vivo model for studying spontaneous ovarian adenocarcinoma....

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Comparative Study 2004; 25(1-2): 87-93 PubMed PMID: 15159690 Citation  Keywords:  Animals, Cerebral Cortex:metabolism, DNA, Complementary:analysis, Dipeptides:physiology, Female, Gene Expression, Gene Expression Profiling, Melatonin:physiology, Mice, Mice, Inbred CBA, Myocardium:metabolism, Oligonucleotide Array Sequence Analysis, Olig.   

OBJECTIVES: Aging is associated with significant alterations in gene expression in numerous organs and tissues. Anti-aging therapy with peptide bioregulators holds much promise for the correction of age-associated changes, making a screening for their molecular targets in tissues an important question of modern gerontology. The synthetic tetrapeptide Cortagen (Ala-Glu-Asp-Pro) was obtained by directed synthesis based on amino acid analysis of natural brain cortex peptide preparation Cortexin. In humans, Cortagen demonstrated a pronounced therapeutic effect upon the structural and functional posttraumatic recovery of peripheral nerve tissue. Importantly, other effects were also observed in cardiovascular and cerebrovascular parameters.

DESIGN: Based on these latter observations, we hypothesized that acute course of Cortagen treatment, large-scale transcriptome analysis, and identification of transcripts with altered expression in heart would facilitate our understanding of the mechanisms responsible for this peptide biological effects. We therefore analyzed the expression of 15,247 transcripts in the heart of female 6-months CBA mice receiving injections of Cortagen for 5 consecutive days was studied by cDNA microarrays.

RESULTS: Comparative analysis of cDNA microarray hybridisation with heart samples from control and experimental group revealed 234 clones (1,53% of the total number of clones) with significant changes of expression that matched 110 known genes belonging to various functional categories. Maximum up- and down-regulation was +5.42 and -2.86, respectively.

CONCLUSION: Intercomparison of changes in cardiac expression profile induced by synthetic peptides (Cortagen, Vilon, Epitalon) and pineal peptide hormone melatonin revealed both common and specific effects of Cortagen upon gene expression in heart....

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Comparative Study 2004; 25(1-2): 70-74 PubMed PMID: 15159686 Citation  Keywords:  Animal Feed, Animals, Antioxidants:physiology, Brain:metabolism, Dose-Response Relationship, Drug, Iodides:administration & dosage, Liver:metabolism, Lung:metabolism, Male, Melatonin:physiology, Oxidative Stress:physiology, Rats, Rats, Wistar, Schiff Base.   

OBJECTIVES: Administration of iodides to animals, living in iodine-deficient areas, can induce necrosis and fibrosis of the thyroid gland. It is believed that structural and functional changes of the thyroid may be related to oxidative processes. Increased lipid peroxidation levels were reported in murine thyroid glands after high doses of iodine. Melatonin (MEL) is believed to exert its effects via electron donation to directly detoxify free radicals, such as, e.g., the highly toxic hydroxyl radical. In numerous reports related to the antioxidative action of MEL, the authors have considered the protective ability of this hormone against peroxidation of lipids. The goal of the study was to evaluate oxidative processes and the protective role of MEL in three organs of the rat (the liver, the brain, and the lungs) during treatment with different doses of iodide.

MATERIAL AND METHODS: Schiff's bases (SB) concentrations (a parameter of oxidative stress) were measured in liver, lung and brain homogenates of male Wistar rats. The animals received iodides in their diet in the following concentrations, for 2 weeks: Group 1--Controls (standard normal-iodine diet, containing approx. 0.7 mg of kalium iodide per kg; KI/kg); Group 2--diet containing 0,25 mg KI/kg; Group 3--diet with 4,0 mg KI/kg; Group 4--diet with 8,0 mg KI/kg. Group 5--standard normal-iodine diet and MEL alone in a dose of 1 mg/kg BW i.p. at 3.00 pm, every day for two weeks. Subsequent three groups (6-8) received KI in their diet in doses as above, respectively, together with MEL.

RESULTS: We noted increased levels of SB in the lungs and in the liver, when compared to those observed in controls. We also found decreased SB concentrations in liver and lung homogenates after an administration of MEL but--unexpectedly--the level of SB increased in the group with the highest dose of iodine in diet in lung homogenates. Increased levels of Schiff's bases suggest that iodine is involved in oxidative processes not only in the thyroid but also in other tissues, and MEL protects against the iodine-induced oxidative stress.

CONCLUSION: Our results confirm the differences in lipid peroxidation among the examined organs. These alterations can possibly be related to different sensitivity rates of examined tissues to oxidative damage....

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Journal Article 2003; 24(6): 392-396 PubMed PMID: 15073562 Citation  Keywords:  Animals, Circadian Rhythm, Male, Melatonin:blood, Models, Animal, Pineal Gland:secretion, Postoperative Complications:metabolism, Pressure, Rats, Rats, Sprague-Dawley, Surgical Instruments,.   

OBJECTIVES: Pineal gland hormone, melatonin, is a current issue of interest for accumulating data concerning its diverse physiological functions. The disturbances in melatonin secretion are observed in different pathological conditions involving pineal regions, but it is not ascertained if those disturbances present any clinical implications. The aim of this work was to examine whether pineal gland compression changes melatonin secretion.

SETTING AND DESIGN: The experiment was carried out on adult rats, divided into four equal groups: (i) control (no surgery was performed), (ii) sham-operated, (iii) with sham pineal gland compression and (iv) with pineal gland compression performed by cotton piece application.

METHODS: The profile of melatonin secretion was assessed in blood samples collected five times daily, every second day, starting from 8 to 14 day following surgery.

RESULTS: We found that surgery itself significantly increased night melatonin secretion in comparison to controls. By contrast, in pineal-gland compressed rats, melatonin secretion was lower than in control group, suggesting that the influence of pineal compression overcame that induced by operation stress.

CONCLUSIONS: In conclusion, we presume that pineal gland compression (like in case of some tumors) results in decrease of the concentration of blood melatonin, that may possibly result in decreased protective action of the indoleamine....

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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....

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