Title : Radio protective activity of serotonin- modulating anti consolidation protein
Abstract:
Due to broad application of γ-radiation in industry, oncological clinics and to recent discovery of its powerful presence in the space, the problem of protection of people from its harmful effects bears significant importance. The first series of studies were carried out on hens (Gallus gallus domesticus) taken from three administrative districts of Baku: Binagady settlement (n=7), Ramana settlement (n=7) and Ganly Gol zone (n=6). γ-radiation levels were measured in soil with the isotope analyzer. The animals were sacrificed and levels of SMAP and cytochrome P-450 were evaluated in the liver and kidneys of the hens using the indirect solid phase ELISA-test. Protein extracts of the liver and kidney were used as antigens. A blood sample was obtained from each hen when they were sacrificed; thin smears were made on glass slides, dried and stained by the Romanovsky-Giemsa dye. Nuclear pathologies were counted using a light microscope at X100 magnification in 1000 erythrocytes of each animal. The highest level of background γ-radiation was found in the settlement of Ramana – 65 µR/h. In the settlement of Binagady, values of background γ-radiation were relatively lower – 30 µR/h. The lowest level of background γ-radiation was observed in Ganly Gel zone (control zone) – 5 µR/h. The results of genotoxic analysis of erythrocytes showed that in the hens from the control zone of Ganly Gel, the number of nuclear pathologies was 6.5±0.6 per 1000 cells. In the hens from the settlements of Binagady and Ramana, the levels were 249.7±5.3 per 1000 cells (p<0.001) and 450.3±6.5 per 1000 cells (p<0.001). Most of the pathologically changed nuclei of the erythrocytes had cigar-like shapes. The results of biochemical monitoring of the three administrative districts of Baku city revealed that elevation of background radiation resulted in the upregulation of SMAP levels in the tissues of hens. The levels of SMAP in the liver (0.149±0.002) and kidney (0.149±0.002) of the animals from Ramana significantly exceeded similar indices of the hens from the control zone Ganly Gel (0.092±0.006, p<0.001 and 0.110±0.001, p<0.001, respectively). Along with this, the levels of SMAP observed in the liver and kidney from hens living in Binagady, which had an intermediate level of radiation, were also intermediate in SMAP elevation compared to the control group (0.107±0.003 and 0.133±0.004, p<0.001). The same pattern was observed with the downregulation of cytochrome P-450. Observed levels of cytochrome P-450 in the liver and kidney of the hens from Ramana were 0.068±0.001 and 0.065±0.002, respectively. These values were significantly lower than those observed in the hens from the control zone of Ganly Gel (0.097±0.009, p<0.05 and 0.1±0.007, p<0.01). In Binagady the levels of cytochrome P-450 in the liver and kidney of the hens reached 0.073±0.003 (p<0.05) and 0.140±0.012 (p<0.05). The second series of studies were carried out on Wistar male rats with body mass 180-210 g. The animals were separated into 3 groups: 1) negative control group (n=7); 2) positive control group (n=7) – administration with inactive SMAP (1 mg per 100 g of body mass) and 3 h later γ-radiation at a dose 8 Gy; 3) experimental group – administration of SMAP and 3 h later 8 Gy γ-radiation. Four days after exposure the animals were sacrificed, bone marrow was isolated and nuclear pathologies per 1000 immature erythrocytes were scored. We observed a sharp (20 fold) increase in nuclear pathologies of the animals of the positive control group – 55.3±3.2 per 1000 immature erythrocytes – relative to the negative control – 2.6±0.4 per 1000 cells (p<0.001). On the other hand, in the rats that received an administration of SMAP prior to γ-radiation, nuclear pathologies were reduced by 41% in comparison to the values of the group receiving inactive SMAP (32.8±1.9 and 55.3±3.2 per 1000 cells, p<0.001). The results of both series indicate to possessing by SMAP of strong radioprotective activity.