title: Effect of melatonin and pineal peptide preparation epithalamin on life span and free radical oxidation in Drosophila melanogaster.
abstract: 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.
authors.affiliation: Laboratory of Experimental Tumors, N.N. Petrov Research Institute of Oncology, St. Petersburg, Russia. anisimov@anisimov.spb.ru
authors.forename: V N
authors.initials: VN
authors.lastname: Anisimov
authors.forename: S V
authors.initials: SV
authors.lastname: Mylnikov
authors.forename: T I
authors.initials: TI
authors.lastname: Oparina
authors.forename: V K
authors.initials: VK
authors.lastname: Khavinson
mesh_terms: D000818:Animals; D002374:Catalase / Q000378:metabolism; D004331:Drosophila melanogaster / Q000187:drug effects*; D005260:Female; D005609:Free Radicals; D015227:Lipid Peroxidation; D008136:Longevity / Q000187:drug effects*; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010455:Peptides / Q000494:pharmacology*; D010870:Pineal Gland / Q000737:chemistry; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D005609:Free Radicals; D010455:Peptides; C027437:epithalamin; D002374:Catalase; D013482:Superoxide Dismutase; D008550:Melatonin