Epithalamin Research & Studies

The effects of melatonin and epithalamin on the content of protein and lipid peroxidation products in the cortex and hippocampus of hypoxic rats were studied under conditions of acute hypobaric hypoxia equivalent to the altitude of 12,000 m. Pineal preparations reduced the intensity of free-radical processes in the brain exposed to acute hypoxia. Epithalamin more effectively than exogenous melatonin protected hippocampal neurons during acute hypoxia by reducing free-radical damage to lipids and proteins.

In contrast to young people, changes in the rhythms of parameters manifested in elderly and senile chronic coronary patients in inversion (decreased T cell count in the peripheral blood, values of lymphocyte blastogenesis test with phytohemagglutinin, and phagocytic index in the fall), monotony (B cell count in the peripheral blood), decreased amplitude of serum hydrocortisone, and desynchronization. The levels of thymic serum factor and IgG were higher in the fall than in the spring, but the seasonal difference leveled after 2.5 years of observation. On the other hand, the rhythms of changes in the thymic serum factor and hydrocortisone were retained in patients with chronic coronary disease after 6 courses of epithalamin by the optimal protocol (period of observation 30 months) and blood T cell count increased in the fall. Improvement of the rhythms of the parameters was associated with a benign clinical course of the disease.

The effect of epithalamin on circadian rhythms of thymic serum factor titers and melatonin concentrations in the blood of elderly people was studied. Course treatment with epithalamin modulated the rhythm of the thymic endocrine function. The increase in the titer of thymic serum factor at night coincided with the increase in blood melatonin concentration and shift of its acrophase to 3.00, which was characteristic of young people. In elderly people with preserved nocturnal peak of the thymic serum factor titer before therapy the nocturnal (3.00) concentration of melatonin was high and did not change after drug therapy. The correlation between melatonin concentration and titer of thymic serum factor increased after epithalamin treatment.

Circadian rhythm of plasma melatonin concentrations in healthy elderly subjects was studied before and after a course treatment with Epithalamin (peptide preparation from the pineal gland). Epithalamin modulated the melatonin-producing function of the pineal gland. During the dark period plasma melatonin concentration increased in subjects with initially lowered activity of the pineal gland, while in subjects with normal epiphyseal function plasma melatonin concentration tended to decrease.

Translocation of cytomedins into the cell is determined by their interaction with cellular membranes. The investigation concerned membrane-associated free-radical reactions in the formed elements of blood incubated with epithalamin. The antioxidative effect of epithalamin on such elements as red blood cells and lymphocytes sampled from breast cancer patients manifested itself as enhanced activity of antioxidative enzymes and elevated concentrations of fat-soluble antioxidative vitamins in the membranes. These changes are likely to be brought about by the intensification of their regeneration from the oxidized forms. It is suggested that the stimulating effect of epithalamin on immunocompetent cells is due to its modulating influence on free-radical reactions. This effect gives epithalamin significant advantage over many immunotropic drugs and makes a case for its large-scale application for immunological rehabilitation of cancer patients.

The review on our own data on the effect of the pineal peptide preparation Epithalamin on free radical processes in rodents and humans is presented in this paper.

Immunohistochemical and morphometric analysis showed that epithalamin and epithalon produced similar effects on the functional morphology of the spleen in pinealectomized rats. Both peptides prevented hyperplasia of lymphoid cells in follicular germinative centers induced by pinealectomy and potentiated the decrease in extramedullary hemopoiesis. These findings confirm the data on functional relationships between the pineal gland and immune system. The effects of epithalamin and epithalon on cell and tissue homeostasis in the spleen of old pinealectomized rats can be regarded as a manifestation of the general regulatory effect of these peptides.

The effects of a single-shot intraperitoneally administration of melatonin in a dose of 1 mg per kg body weight and epithalamin in a dose of 2.5 mg per kg body weight on the activities of Na+, K(+)-ATPase and 5'-nucleotidase were investigated in the forebrain of juvenile male white rats under the acute hypobaric hypoxia. The melatonin and epithalamin administration against the background of acute hypoxia prevented an acute hypoxia inducing decrease in the activity of Na+, K(+)-ATPase as well as increased in the activity of 5'-nucleotidase. Such effects of pineal hormones can promote antihypoxic protection of neurons.

Epithelamine made in Russia (Samson, St. Petersburg) was tried for effects on carbohydrate metabolism and cardiovascular system in 33 patients with non-insulin-dependent diabetes mellitus (NIDDM). Adjuvant use of epithelamine in combined treatment of NIDDM promoted a stable compensation of carbohydrate metabolism, lowering of glycosylated hemoglobin, immunoreactive insulin. There was also a moderate hypotensive effect and improvement of left ventricular diastolic function.

Treatment with pineal peptide preparation epithalamin was followed by the increase of the mean lifespan of female D. melanogaster, SHR mice, C3H/Sn mice and LIO rats by 11-31% (P < 0.05). Ninety percent mortality as well as maximum lifespan were increased in fruit flies, C3H/Sn mice and rats. Mortality rate was decreased by 52% in D. melanogaster, by 52% in rats, by 27% in C3H/Sn mice. It did not change in SHR mice exposed to epithalamin. Treatment with the pineal peptide increased MRDT in flies, C3H/Sn mice and rats. It has been shown that epithalamin increased synthesis and secretion of melatonin in rats and inhibits free radical processes in rats and in D. melanogaster. It is suggested that antioxidative properties of epithalamin lead to increased lifespan of three different animal species.

It was shown previously that epithalamin delays age-related changes in reproductive and immune systems and increases the life span of mice and rats. These effects could be mediated by stimulating influences of epithalamin on synthesis and secretion of melatonin and on free radical processes. A comparative study on the effect of epithalamin and melatonin on both the life span of Drosophila melanogaster (strain HEM) and on the intensity of lipid peroxidation and activity of antioxidative enzymes in their tissues was the main aim of this work. Melatonin and epithalamin was added to the nutrition medium (100 micrograms/ml) during 2-3rd age of larvas. For survival analysis the flies were passed (five coupes per vessel) each 3-7 days. Lipid peroxidation was evaluated as the level of ketodienes (KD) and conjugated hydroperoxides (CHP) in fly tissues at the age of 11 days. Activity of Cu, Zn-superoxide dismuatse (SOD) and catalase was evaluated as well. The mean, median and maximum life span (MLS) were estimated. Mortality rate (MR) was calculated as alpha in the Gompertz equation (R = Ro (exp alpha t) and mortality rate doubling time (MRDT) as in 2/alpha. These parameters in groups of male and female flies exposed to melatonin and in male flies exposed to epithalamin were no different from the parameters for controls. However, exposure to epithalamin was followed in females by a significant increase in mean life span (by 17%, P < 0.02), of median (by 26%), of MLS by 14% and by a 2.12 times decrease of MR (P < 0.01) and MRDT (by 32%) compared with female controls. The level of CHP and KD in the tissues of male control flies was 40 and 49% less than that in females and indirectly correlates with male life span. Exposure to melatonin was followed by a decrease in the level of CHP and KD in females and the deletion of sex differences in them. Exposure to epithalamin significantly decreased the level of CHP and KD in female flies compared to controls (2.3 and 3.4 times, respectively, P < 0.001). Exposure to melatonin failed to influence the activity of catalase in males but increased it in females by 24% (P < 0.02) and failed to influence SOD activity both in males and females. Exposure to epithalamin was followed by a significant increase in activity of catalse, 20% in males and 7% in females and by an increase in SOD activity in males (41%). Thus, it was shown that exposure to epithalamin significantly increases the mean life span and MLS of female D.melanogaster and slowed down their aging rate by 2.12 times. This effect is in good agreement with the inhibiting effect of epithalamin in lipid peroxidation processes in fly tissues.

The biosynthesis of serotonin into melatonin was decreased in old (18-20-month) in comparison to young (4-5-month) male Wistar rats. 5-day morning injections to young and old rats with polypeptide pineal preparation (epithalamin) in a dose of 2.5 mg/kg of body weight induced the increase in the night peak of serotonin, N-acetylserotonin and melatonin in young and melatonin alone in old rats and did not influence 5-methoxytryptamine, 5-oxy- and 5-methoxyindoleacetic acids level. These data support suggestion of ultrashort loop between pineal peptides and indoles and that epithalamin increases the metabolism of serotonin into melatonin.

5-day morning injections to pubertal male rats of polypeptide epithalamin preparation obtained from cattle epiphysis, in dose of 0.25 mg/100 g body mass induced the increase of serotonin epiphyseal concentration night peak, N-acetylserotonin and melatonin and didn't produce any essential influence on 5-methoxytryptamine, 5-oxy- and 5-methoxyindoleacetic acid level. It has been concluded, that epiphyseal peptides and indoles interact according to ultrashort connection, epiphyseal peptides point of application is the reaction of tryptophan transformation into serotonin and its further metabolism in N-acetylserotonin and melatonin. It has been suggested that the increase of epiphyseal melatonin production is on the basis of epithalamin therapeutic action.

The effect of thymalin and epithalamin on dissemination of tumors treated by pulsed laser radiation was studied in C57B1 female mice bearing subcutaneously transplanted melanoma B16 and Lewis carcinoma. Radiation was delivered from TOC-1001 neodymium laser, wave-length of 1,060 nm, pulse duration--1 msec and fluence--350-400 J/cm2. Drug dosage was 1 mg. Thymalin and epithalamin treatment potentiated the preventive effect of laser radiation on tumor dissemination. Application of the said agents was followed by an increase in antibody-producing cells (as measured by Jerne's procedure) in the spleen of irradiated melanoma B16--bearing mice.

The influence of epithalamine on the blood content of immunoreactive follicle-stimulating and luteinizing hormones and prolactin was studied in 49 persons of both sexes and albino rats. It was shown that epithalamine promotes an increase in the concentration of the blood hormones if their initial level is lowered and vice versa. The normal hormone content is not changed under one epithalamine injection. The epiphysis-hypophysis relationships are discussed.