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The Protective Effects Of Syringaldehyde Metabolites On Irradiation Damage Of Mouse Embryonic Fibroblasts And Bone Marrow

Posted on:2014-04-25Degree:MasterType:Thesis
Country:ChinaCandidate:M SongFull Text:PDF
GTID:2254330401968989Subject:Pathology and pathophysiology
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In the human beings living environment, ionizing radiation threatens people’shealth every moment.People have been seeking an effective drug against ionizingradiation. Nowadays, there are few radio-protectors which are widely used in theclinical and have satisfactory results. It becomes more important to find a highefficiency and low toxicity activity and fewer adverse reactions radio-protectors.Researchers at home and abroad pay a lot of attention to radio-protectors.Except forthe sulfur-containing compounds,the cell growth factor, natural medicine, there arealso many studies focus on the anti-radiation effects of cytokines, herbs andcompound, estrogen.Natural compounds vanillin, it hasbeen shown that vanillin has the activityofantioxidant and anti-mutagenic.It can clear free radicals and inhibit DNA andchromosome damage by ionizing radiation. However, its effectiveness ofradioprotection only occurred at very high concentration and its activity is relativelow.So, our laboratory screened a derivative of vanillin–syringaldehyde, which hasbetter radio-protective effect. It confirmed that syringaldehyde is more effective inscavenging free radicals than vanillin. It can reduce radiation-induced DNA damage,and improve damaged cell DNA repair ability and the survival rate of radiated cell.syringaldehyde is easy to synthetize and its chemical physicochemical property isstable. So it has value to be developed as a novel radiation protection drug.Pharmacokinetic research finds that syringaldehyde can be absorbed by the animalafter10~15min of being injected; the dose reaching in the blood circulation wassignificantly lower than the dose given to animal at the beginning. There are a lot ofsyringic acid and few syringic alcohol can be detected in plasma. Therefore, wespeculate that syringaldehyde being injected into the body, its major metabolite---syringic acid or two metabolites (syringic acid and syringic alcohol mixed, referred toas mixture)have synergies. The research project focuses on study onpharmacodynamic part, through a series of experimentson MEFs.We observe and compare syringaldehyde major metabolite--syringic acid and mixtures ofradio-protective effect. Through a series of experimentson animals, we study thesyringaldehyde major metabolite--syringic acid of protective effect on radioactiveoxidative damage and radioactive hematopoietic injury. It provide experimental basisfor further clinical application of syringaldehyde. The main findings are as follows:1. MTT assay to observe the effect of syringaldehydemetabolites on MEFs afterradiation, the results showed thatcompared with0μmol/L group, the OD value ofeach dosing group was significantly increased (p<0.01), which indicates thesyringaldehyde metabolites can effectively reduce the damage of MEFsafter radiation.2. MTT assay to observe the impact of syringaldehyde metabolites on MEFs cellviability after radiation, the results showed thatcompared with the IR group, the ODvalue of each dosing group was significantly increased (p<0.01), which indicates thesyringaldehyde metabolites can improve viability of MEFs after radiation,3. Cell proliferation experiment to observe the influence of syringaldehydemetabolites on MEFs growth. Through the cell growth curve, we find thatcomparedwith the IR group, syringaldehyde metabolites can promote proliferation of MEFsafter radiation.4. Cell colony formation ability assay to detectthe influence of syringaldehydemetabolites on colony forming of MEFs, the results show thatcompared with the IRgroup, dosing group can improve cell colony formation rate, the difference wasstatistically significant (p<0.01), which indicates the syringaldehyde metabolites canimprovethe rate of cell colony formation.5. Countingbone marrow nucleated cells and observingthe effect of syringic acid onhematopoietic injury, compared with IR group, the difference was statisticallysignificant (p<0.01), which indicates syringic acid plays a certain role in mouse bonemarrow nuclear cells radiation protection and can reduce mouse bone marrowhematopoietic injury.6. Fowcytometry to detect nuclear apoptosis of mouse bone marrow, the results showthatcompared with IR group, the difference was statistically significantp<0.01); whichindicates syringic acid can reduce radiation-induced nucleated cell apoptosis inmurine bone marrow. 7. After radiation, disposing mouse bone marrow and spleen tissue,histopathologicalchanges in light microscopy in the treatment of bone marrow and spleen of theanimals in each group, the results show that compared with IR group, syringic acidgroup mouse bone marrow and spleen tissue injury is significantly reduced.8.By the kit to detect the anti-oxidation of syringic acid on mouse after radiation,compared with IR group, Syringic acid group in the3d and6d, SOD activity recoveryare more significant after irradiation, the difference was statistically significant(p<0.01), which indicates syringic acid can promote the recovery of serum SODactivity and reduce the serum MDA content at the same time. Compared with IRgroup, the difference was statistically significant (p<0.01), syringic acid can enhancecellular free radical scavenging capacity, reduce the degree of radiation-inducedmembrane lipid peroxidation injury, so reduce the radiation damage of cells.In conclusion, syringaldehyde metabolites have radio-protective effect on MEFcells; syringaldehyde major metabolite--syringic acid also has radio-protective eeffect against oxidative damage and hematopoietic injury. It can provide experimentalbasis for further clinical application ofsyringaldehyde.
Keywords/Search Tags:syringaldehyde metabolites, radioprotectors, radiation damage
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