Minocycline increases the life span and motor activity and decreases lipid peroxidation in manganese treated Drosophila melanogaster.

The objective of this study was to investigate the effect of Minocycline in the life span, motor activity, and lipid peroxidation of Drosophila melanogaster treated with manganese. Two days after emerging from the pupa male wild-type D. melanogaster were fed for 13 days with corn media containing 15 mM manganese. Then, they were divided in six groups of 300 flies each: group (a) remained treated with manganese (Mn group); group (b) began treatment with Minocycline (0.05 mM) (Mn-Minocycline group); group (c) received no additional treatment (Mn-no treatment group); group (d) simultaneously fed with manganese and Minocycline (Mn+Minocycline group). Additionally, a control (group e) with no treatment and another group (f) fed only with Minocycline after emerging from the pupa were added. All the manganese treated flies (group a) were dead on the 25th day. The life span in group f (101.66±1.33 days, mean S.E.M.) and of group b (97.00±3.46 days) were similar, but in both cases it was significantly higher than in group e (68.33±1.76 days), group c (67.05±2.30 days) and in those of group d (37.33±0.88). Manganese (groups a and d) decreased motor activity in D. melanogaster. In the Minocycline fed flies (groups b and f) a higher motor activity was detected. In Mn-Minocycline and Mn+Minocycline treated flies a significant decrease of MDA levels was detected when compared to the Minocycline group indicating that Minocycline and Mn appear to have a synergistic effect. In conclusion, Minocycline increased the life span and motor activity and decreased MDA formation of manganese treated D. melanogaster, probably by an inhibition of the production of reactive oxygen species. Manganese also exerted an antioxidant effect as shown by the significant decrease of MDA levels when compared to control flies.

Melatonin treatment enhances the efficiency of mice immunization with Venezuelan equine encephalomyelitis virus TC-83.

To determine whether treatment with melatonin (MLT) improves the efficiency of immunization against Venezuelan equine encephalomyelitis (VEE) virus, mice were vaccinated with TC-83 VEE virus and treated daily with MLT (1 or 5 mg/kg) starting 3 days before immunization, until 10 days after. IgM antibody titers were determined at days 7, 14, and 21 post-immunization. IL-10 levels were assayed at day 14 postvaccination. Treatment with MLT increased antibody titers 14 days after the immunization. IL-10 levels also increased with MLT treatment (1 and 5 mg/kg). Mice were challenged with live VEE virus at day 21 postimmunization, and viral titers were plaque assayed in chicken embryo fibroblasts 4 days after the infection. Following this challenge brain virus levels were significantly reduced. The results suggest that MLT treatment enhances the efficiency of mice immunization against VEE virus.

High intensity light increases olfactory bulb melatonin in Venezuelan equine encephalitis virus infection.

In mice infected with the Venezuelan equine encephalomyelitis (VEE) virus and exposed to high intensity light (2500 lux) with a 12 h light: 12 h dark photoperiod, a significant increase in the levels of melatonin in the olfactory bulb was observed. The significance of these findings deserves further studies to understand the mechanisms involved in this effect since the olfactory bulbs have been proposed as first portal for VEE virus entry into the CNS. The increase in melatonin content could represent one of the mechanisms of defense against the viral attack.

Melatonin prolongs survival of immunodepressed mice infected with the Venezuelan equine encephalomyelitis virus.

Male albino mice immunodepressed after the injection of dexamethasone (DEX) were inoculated intraperitoneally with the Guajira strain of Venezuelan equine encephalomyelitis (VEE) virus. Melatonin (MLT) was administered daily, at a dose of 500 micrograms/kg bodyweight, for 3 days before virus inoculation and 10 days after. Serum levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL-2) were determined in all the experimental groups (control, DEX, DEX + MLT, DEX + VEE, DEX + VEE + MLT, VEE and MLT). At day 6 after the virus inoculation, the survival rate was significantly increased from 0% in group DEX + VEE to 32.5% in the group of immunodepressed infected mice treated with MLT (DEX + VEE + MLT). By day 10 a survival rate of 10% was found in group DEX + VEE + MLT and 0% in group VEE. No alterations in IL-2 serum levels were observed. MLT increased GM-CSF in control and in DEX-treated mice. In the VEE virus-infected mice treated with DEX, serum levels of GM-CSF increased progressively from day 1 to 5 postinoculation. In contrast, the levels of GM-CSF in infected immunodepressed mice treated with MLT decreased significantly from day 1 to 5 postinoculation. At day 5 after viral inoculation, no differences were detected in the cerebral viral titres in groups VEE, DEX + VEE and DEX + MLT + VEE. These results show that MLT does not inhibit VEE viral replication in the brain of immunodepressed mice.

In mice the efficiency of immunization with Venezuelan Equine Encephalomyelitis virus TC-83 is transiently increased by dehydroepiandrosterone.

To determine whether treatment with dehydroepiandrosterone (DHEA) improves the efficiency of immunization against the Venezuelan Equine Encephalomyelitis (VEE) virus, mice were vaccinated with the TC-83 VEE virus. DHEA (10 mg/kg) was administered in a single dose, 4 hours before vaccination. IgM antibody titers were determined at days 7, 14 and 21 post-immunization. Treatment with DHEA increased antibody titers at day 14 after immunization. Mice were challenged with live VEE virus at day 21, and viral titers were plaque assayed in chicken embryo fibroblasts from days 2 to 5 post-infection. After the challenge, viremia decreased on day 2 and brain virus levels were reduced at day 4 in mice treated with DHEA. These results suggest that DHEA treatment could enhance the efficiency of immunization against VEE virus in mice.