Melatonin and colon carcinogenesis. III. Effect of melatonin on proliferative activity and apoptosis in colon mucosa and colon tumors induced by 1,2-dimethylhydrazine in rats.

Forty-eight two-month-old outbred female LIO rats were injected weekly with a single dose of 1,2-dimethylhydrazine (DMH; 21 mg/kg of body weight) administered s.c. for 15 consecutive weeks. From the day of the 1st injection of the carcinogen the part of rats were given five days a week during the night time (from 18.00 h to 08.00 h) melatonin dissolved in tap water, 20 mg/l. 10 rats were treated similarly with solvents and served as control. The experiment was terminated 6 months after the first injection of the carcinogen. Colon tumors (mainly adenocarcinomas) developed in a hundred percent of rats exposed both to DMH or to DMH plus melatonin. However, descending colon carcinomas were observed in 65 % of rats exposed to DMH plus melatonin against 100% in those exposed to DMH alone (p < 0.01). The multiplicity of colon tumors was also reduced in rats under the influence of melatonin. This effect is correlated with the significant inhibitory effect of the pineal hormone on mitotic index and with stimulating effect of melatonin on the relative number of apoptotic cells (TUNEL-method) in colon tumors. Long-term treatment with melatonin was followed also by the decrease in the area of lymphoid infiltrates in the colon mucosa of tumor-bearing rats.

[Innervation of grouped lymphoid nodules (Peyer's patches) by the enteric nervous system and the topography of their interior neural elements in the rat]. / Dlitel'naia morfofunktsional'naia sokhrannost' srezov gippokampa morskoi svinki posle kratkoi obrabotki ingibitorami tsiklooksigenaz.

Using the complex of histological methods (staining with toluidine blue, silver nitrate impregnation and application of retrograde fluorescent dye primulin) the data on the neural elements spatial localization within Peyer patches of the small intestine and their connections with the rest of enteric metasympathetic nervous system in rat was obtained. Submucosal plexus that is significantly developed within this lymphoid organ and is divided into internal and external plexuses was found to be most essential to the innervation of rat Peyers patches. These plexuses innervate all Peyers patch areas:nodules, cupula and internodular zones and the nodule-associated epithelium. Moreover, it was shown that within Peyers patch the plexuses form an integral part with the rest of the enteric nervous system and possess close connections with ganglia that are distant from the patch and are related both to submucosal and myenteric nervous plexuses. Direct inputs into Peyers patch nervous plexuses from extramural ganglia are present as well. These data was considered as a morphological basis for functional interaction of nervous and immune systems within the enteric immune organ and for possible enteric nervous system regulation of immune functions.

[The effect of cycloferon administration on the growth of transplantable tumors in rats and mice]. / Vliianie tsikloferona na rost perevivaemykh opukholei u krys i mysheii.

The influence of cycloferon and its combinations with cyclo-phosphamide on the growth of transplantable tumors was studied in rats with lymphosarcoma of Pliss and CBA and NMRI mice bearing Ehrlich's carcinoma and leukemia L1210. While cycloferon alone failed to significantly influence tumor growth, treatment with 100 mg/kg of the drug was followed by longer survival in mice with transplantable Ehrlich tumor. The highest inhibitory effect of combined cycloferon and cyclophosphamide was recorded on day 10 when tumor growth inhibition was as high as 90%. Mitotic activity of tumor was inhibited following multiple treatment with cycloferon, in combination with cyclophosphamide and cyclophosphamide alone. Survival longer than in control was registered only in animals with L1210 receiving cyclophosphamide alone or in combination with cycloferon. Cycloferon administration was shown to inhibit the growth of Pliss lymphosarcoma only within a short period after the start of the study. Combined treatment with cycloferon and cyclophosphamide produced the highest inhibition. The antitumor effect of cycloferon varied depending on tumor pattern, species and line of animals and dose and modality of administration.

[The effect of melatonin on the indices of biological age, on longevity and on the development of spontaneous tumors in mice]. / Vliianie melatonina na pokazateli biologicheskogo vozrasta, prodolzhitel'nost' zhizni i razvitie spontannykh opukholei u myshei.

Fifty female CBA mice were given melatonin with drinking water (20 mg/l) for 5 consecutive days monthly, beginning from the age of 6 months, until natural death. Another 50 intact mice were used as controls. Melatonin failed to significantly influence body weight or food consumption. Age-related switching-off of estrus function was delayed, body temperature decreased. Somewhat decreased motor activity did not affect physical one or endurance. Increase in life span led to higher spontaneous tumor incidence. Another experiment using 20 animals of the same line showed melatonin to inhibit free-radical processes. A conclusion was drawn that caution should be exercised before melatonin is recommended for long-term administration as a geroprotector.

[The lateralization effect of oxytocin on the functional activity of paired visceral organs in rats]. / Lateralizovannoe vliianie oksitotsina na funktsional'nuiu aktivnost' parnykh vistseral'nykh organov u krys.

Following unilateral intranasal oxytocin administration, asymmetric alterations in some functional parameters of the adrenal glands, testis, lungs and heart, occurred. The lateralization of alterations was dependent on the side of oxytocin injection and the side of paired organ arrevgenent. Possible pathways of intranasal oxytocin administration effects on visceral organs as well as causes of their asymmetry, are discussed.

[Effect of pineal peptide on parameters of the biological age and life span in mice]. / Vliianie peptida épifiza na pokazateli biologicheskogo vozrasta i prodolzhitel'nost' zhizni myshei.

Female CBA mice were injected with s.c. synthetic tetrapeptide Epithalon from a 6-month age until death. The drug failed to affect the body weight or food consumption, physical activity or behavioural parameters. However, it slowed down the age-related switching off of the estrus function, decreased body temperature, decelerated free redical processes, prolonged the mice life span with an accompanying drop in spontaneous tumour incidence.

Effect of vilon on biological age and lifespan in mice.

Subcutaneous administration of vilon (Lys-Glu) to female CBA mice starting from the 6th month of life increased physical activity and endurance, decreased body temperature, prolonged the lifespan, and prevented the development of spontaneous neoplasms. Vilon had no effect on age-related changes of estrous function and free radical processes. Long-term administration of vilon caused no unfavourable effects on animal development. The obtained results show safety of chronic vilon administration and allow to use this preparation for geroprotection and prophylaxis of age pathology.