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Marková M., E. Adámeková, P. Kubatka, B. Bojková, E. Ahlersová, I. Ahlers: Effect of Prolonged Melatonin Administration on Metabolic Parameters and Organ Weights inYoung Male and Female Sprague-Dawley rats. Acta Vet. Brno 2003, 72: 163-173.The question of the introduction of melatonin as a drug remains still open. Especially the long term melatonin administration have to be analysed and discussed. The aim of present study was to analyze the effect of low doses of melatonin (4 µg/ml of tap water) administered for 70 days, daily from 15.00 to 08.00 h (from 08.00 to15.00 h animals were drinking tap water) on selected metabolic parameters in male and female Sprague-Dawley rats. In addition to concentration/content of triacylglycerols, phospholipids, cholesterol, malondialdehyde, glucose and glycogen in the serum and tissues, serum corticosterone and insulin, weights of selected organs, periovarial and epididymal fat and body weight were recordered. Melatonin was not administered to control groups. Oral glucose tolerance tests were carried out before melatonin administration and 9 weeks thereafter.Male and female rats aged 5 weeks were adapted to standard vivarium conditions and artificial light regimen L:D-12:12 h. The animals were fed MP diet containing 2.5 % fat at least and drank tap water or melatonin solution ad libitum. The rats were weighed twice a week and food and water intake was recorded. After 10 weeks they were sacrificed, organs and tissues were weighed and the aforementioned metabolic parameters were determined in the serum, liver, heart muscle and bone marrow (femur).Melatonin administration decreased significantly the serum triacylglycerol concentration and liver glycogen content in male rats, and it increased liver the phospholipid content in females. Melatonin did not acutely modify the values of other metabolic parameters. Prolonged melatonin administration significantly increased the weight of heart muscle and periovarial fat in females, in males significantly reduced the weight of adrenals, liver, heart muscle and epididymal fat as well as their body weight from day 19 to the end of experiment. Body weight in MEL-drinking females was similar to that in controls. Water and food intake in MEL-drinking males did not differ from controls, in females was temporarily increased in week 6.Prolonged melatonin administration did not significantly influence the glycemia level. The oral glucose tolerance test curves were normal before melatonin administration; one abnormal curve (out of 9 individuals) in the female group and 2 abnormal curves in the male group (out of 9 individuals) were recorded 9 weeks after melatonin administration. Prolonged melatonin treatment resulted in sexual differences in body weight, epididymal and periovarial fat, and heart muscle weight. Melatonin, metabolic and hormone responses, body and organ weightsAlthough pineal gland is the main site of melatonin (MEL) synthesis in mammals its synthesis has been proved in the retina, extraorbital lacrimal glands, Harder's glands...

Bojková B., M. Marková, E. Ahlersová, I. Ahlers, E. Adámeková, P. Kubatka, M. Kassayová: Metabolic Effects of Prolonged Melatonin Administration and Short-Term Fasting in Laboratory Rats. Acta Vet. Brno 2006, 75: 21-32.The aim of this work was to evaluate the effect of prolonged administration of the pineal hormone melatonin and short-term fasting on metabolic variables in male and female Wistar:Han rats. Melatonin (MEL, 4µg/ml of tap water) was administered daily since the 5 th week of age. The control group drank tap water. Rats were fed a standard type of diet ad libitum and were kept in the light regimen L:D -12:12 h. The experiment was terminated after 11 (variant B) or 12 (variant A) weeks of MEL administration. The animals were sacrificed by quick decapitation following overnight fasting (variant A) or 48-h fasting (variant B). Selected organs and tissues were removed and weighed and selected metabolic variables in the serum and tissues were determined.MEL decreased body mass independent of food and water intake in both sexes. In males (variant A) MEL increased the weight of the heart muscle, spleen and adrenals; it decreased the absolute weight of epididymal fat and increased serum corticosterone and phospholipids concentration in comparison with controls. In females, serum glucose decrease and liver triacylglycerols increase were found. After 48-h fasting (variant B) liver, spleen and adrenal weight increase in MELdrinking females was found. In males MEL increased the thymus weight and decreased the epididymal fat weight. In both sexes MEL increased serum corticosterone and liver glycogen concentration; MEL increased serum glucose in males and serum cholesterol concentration in females. Changes in the evaluated variables were also related to fasting duration prior to decapitation.A 48-h fasting at the end of the prolonged MEL intake (variant B vs. A) decreased the absolute liver weight in both sexes and the epididymal/periovarial fat weight, and increased thymus weight in males. In females it decreased the absolute heart muscle weight and increased the spleen weight. In males, 48-h fasting increased serum corticosterone and phospholipids concentration; it decreased the liver triacylglycerols content in females and the liver cholesterol content in males and females. In both sexes 48-h fasting increased glucose concentration in the serum and glycogen concentration in the liver and heart muscle as well as triacylglycerols and cholesterol concentration in the serum, phospholipids concentration in the liver and bone marrow and decreased malondialdehyde concentration in the liver. Forty-eight hour fasting after prolonged MEL administration resulted in a wider range of carbohydrate and lipid metabolism alterations of young rats of both sexes. Melatonin, prolonged administration, metabolic variables, short-term fastingMelatonin (MEL), the main pineal hormone, is a substance of numerous physiological effects. In addition to epiphysis, MEL is synthesized in other tissues too -e.g. in the retina, extraorbi...

Marková M., E. Adámeková, B. Bojková, P. Kubatka, M. Kassayová, E. Ahlersová, I. Ahlers: Effect of Low-dose Chronic Melatonin Administration on Metabolic and Hormonal Variables in Young Laboratory Rats. Acta Vet. Brno 2004, 73: 445-453.The introduction of melatonin (MEL) as a drug remains open due to insufficient data about the effects of its long-term administration on metabolism. We explored effects of MEL given for 26 weeks at low doses, 4 µg/ml of tap water, on selected metabolic and hormonal indices in young female and male Sprague-Dawley rats.Male and female rats aged 5 weeks were adapted to standard housing conditions and artificial light regimen L:D = 12:12 h. The animals were fed standard laboratory diet and drank tap water (controls) or MEL solution ad libitum. Body weight gain, food and water intake was regularly recorded. Oral glucose tolerance tests (OGTTs) were carried out before and 24 weeks after MEL administration. At the end of the experiment following an overnight fast the animals were sacrificed, selected organs and tissues were weighed, selected metabolic indices and hormone concentrations were determined in the serum, liver, heart muscle and bone marrow (femur).Chronic MEL administration increased in females serum corticosterone concentration, decreased glycogen concentration in the liver and heart muscle, increased triacylglycerol concentration in the bone marrow. An increased absolute weight of periovarial fat and body weight gain were found in last 5 weeks of the experiment. In males, MEL decreased insulin concentration in the serum and body weight gain from week 2 to week 17 of its administration; it decreased relative liver weight in males and females. MEL did not alter food or water intake in both sexes. MEL treatment decreased glucose tolerance (i.e. reduced area under curve values in OGTTs) in males and prolonged the return of afterload glycemia values to initial level in females.Alterations of carbohydrate metabolism regulation and of body weigth gain were found in both sexes of young rats after long term melatonin administration.

Chamilová M., P. Kubatka, K. Kalická, E. Adámeková, B. Bojková, I. Ahlers, E. Ahlersová: Chemoprevention of N-methyl-N-nitrosourea Induced Mammary Carcinogenesis with Raloxifene and Melatonin: Metabolic Changes in Female Rats. Acta Vet. Brno 2002, 71: 235-242.The aim of this work was to determine the selected parameters of carbohydrate and lipid metabolism in the mammary carcinogenesis induced with N-methyl-N-nitrosourea (NMU) in two doses, each by 50 mg/kg of body weight with a 7-day interval between them within the postnatal days 43 and 54 in female Sprague-Dawley rats. Chemoprevention started with the administration of melatonin (MEL, 4 µg/ml in water, from 15.00 h to 08.00 h) 12 days and raloxifene (RAL 5 mg/kg, 2 × weekly) 10 days before the application of NMU. Twenty-four weeks following the NMU administration the animals were killed, and the incidence, latency, frequency and volume of tumours were evaluated. The animals were divided into: tumour-bearing (TB) and non-tumourbearing (NTB) with the influence of RAL, MEL and their combination. While RAL and RAL plus MEL significantly decreased the incidence and frequency of tumours, the effect of isolated MEL was substantially lower. In the serum, an increase in the concentration of serum glucose in TB and also NTB animals was observed. In the liver of both the TB and NTB animals, the content of cholesterol (CH) and triacylglycerols (TG) decreased and the contents of phospholipids (PL) increased. RAL decreased the contents of CH and PL in the liver of NTB animals and increased the concentration of TG in both groups of animals. Administration of RAL to NTB animals decreased the concentrations of malondialdehyde (MDA) in the serum and thymus, in the bone marrow also in TB animals. MEL decreased the concentration of MDA in the bone marrow of TB animals. MEL increased the concentrations of serum glucose and glycogen content in the heart muscle of NTB animals. RAL plus MEL decreased the concentration of serum TG and PL and decreased the contents of CH and PL in the liver of TB as well as NTB animals. In the thymus and liver, combination of RAL+MEL decreased the MDA content compared with the RAL alone in NTB animals.The co-effect of two or more substances will be probably the optimal way in prevention of cancer. The co-effect of RAL and MEL shows to be a prospective way for influencing the mammary tumors. Breast cancer, female rats, raloxifene, melatonin, chemopreventionThe hormonal therapy of the breast carcinoma is an inseparable part of the variety of therapeutic procedures. The substitution with estrogens has been considered for a long time as a dominant indication of therapy in postmenopausal women, and it has been recognized that approximately one third of women will have a benefit of this procedure. The use of estrogens protects these women against osteoporosis and decreases the cardiovascular risk, but on the other hand, increases the risk of breast and endometrium carcinoma (Col et al. 1997). With regard to the unfavourable effects of estrogens on ...