In this paper the chemopreventive effect of peroral antidiabetic metformin in mammary carcinogenesis in female SpragueDawley rats was evaluated. Mammary carcinogenesis was induced by N-methyl-N-nitrosourea (NMU) administered in two intraperitoneal doses each per 50 mg/kg b.w. between 43.-55. postnatal days. Metformin was administered in drinking water (at a concentration of 50 µg/ml and 500 µg/ml) 13 days before the first NMU dose until the termination of the experiment. During the experiment the animals were weekly weighed and palpated for the presence of mammary tumors, the incidence, latency, tumor frequency, and tumor volume were recorded. The experiment was terminated 18 weeks after the first NMU dose, basic tumor growth parameters and metabolic and hormonal variables were evaluated. Metformin did not significantly alter the tumor growth although a delay in tumor onset was recorded after higher metformin dose. Metformin altered metabolic and hormonal variables. Insulinemia decreased after both metformin doses in comparison with intact rats without changes in glycemia, triacylglycerols concentration was decreased in liver and increased in serum when compared to intacts. Higher metformin dose attenuated lipoperoxidation in liver.

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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...

Data available from in-vitro and in-vivo studies suggest oncostatic properties of peroral antidiabetics, thiazolidinediones, in many types of cancer. This study is the first report on the chemopreventive effect of pioglitazone in mammary carcinogenesis in rats. Mammary carcinogenesis was induced by N-methyl-N-nitrosourea administered in two intraperitoneal doses per 50 mg/kg bodyweight on the 43rd and 50th postnatal days. Pioglitazone was administered in the diet at concentrations of 10 and 100 ppm, respectively, 12 days before the first carcinogen dose until the termination of the experiment. During the experiment, the animals were weighed weekly and palpated for the presence of mammary tumors, and the incidence, latency, tumor frequency, and tumor volume were recorded. The experiment was terminated 17 weeks after the first carcinogen dose; basic tumor growth parameters and metabolic and hormonal variables were evaluated. Pioglitazone at higher concentration decreased incidence and frequency per group from the 11th week of experiment when compared with the control group and a group receiving a lower dose. Pioglitazone at a higher dose decreased the final incidence by 38%, frequency per group by 63%, and extended latency period by 32% when compared with the control group. Our data suggest that pioglitazone and other glitazones should be further investigated for oncopreventive effects.

The aim of this work was to evaluate the effect of prolonged melatonin administration on chosen metabolic and hormonal variables in male and female Sprague-Dawley rats. Melatonin was administered in tap water (4 microg/ml) daily from the 6th month of age. Rats were fed a standard type of diet ad libitum and were kept in a light regimen L:D--12:12h. The experiment was terminated after 12 weeks of melatonin administration. Melatonin decreased body mass during the whole experiment in females and from the 42nd day of the experiment in males. Relative heart muscle weight in females and absolute/relative thymus weight in males were increased after melatonin administration. Melatonin decreased glycaemia, heart muscle glycogen concentration in females and liver glycogen concentration in both sexes. Serum insulin concentration in males was decreased; serum corticosterone concentration was increased in both males and females. Serum triacylglycerol and heart muscle cholesterol concentration in females were decreased, however in males serum and heart muscle cholesterol concentration was increased. Liver phospholipid concentration in females was decreased and heart muscle phospholipid concentration in males was increased. Melatonin increased malondialdehyde concentration in heart muscle in males and in liver in both sexes. Melatonin induced prominent sex-dependent changes in both carbohydrate and lipid metabolism.