| Summary: | 碩士 === 國立彰化師範大學 === 生物技術研究所 === 101 === Gallic acid (GA), an occasionally applied nutraceutics, is profoundly distributed in vegetables and fruits. Documented risks of GA administration include cytotoxicity, peroxidative capability, hemorrhagic anemia, abortion and still birth. The teratogenicity of GA in embryos is still unclear. Using the Chicken Embryo Model (CEM) we studied the pathological, biochemical, and cytotoxicological events when GA is administered alone and its preventive and rehabilitative strategies. Results revealed GA to be a teratogenic, which could induce malformation of cervical muscles, angiogenesis, inflammatory edema, hemorrhagic liposis and necrosis. Genes HIF-1a and TNF-a, and IL-6 and NFkB were all upregulated (p<0.05) with simultaneous downregulation of the ratio genes VEGF-r2 to VEGF-a, all showing dose-responsive manners. The cause of hemorrhagic inflammation was due to the stimulation of TNF-α to tissues through both the typical and atypical pathways. Alternatively, GA, despite of in vitro or in vivo, tends to deplete the dissolved oxygen (DO) and at the same time converts itself into semiquinone and quinones, to facilitate the production of ROS, resulting in exhaustion of the glutathione in RBC and eventually hemolysis to release the ferrous ions. On the other hand, the CPT1 in the cervical muscles was also significantly downregulated, hence the b-oxidation was severely blocked, resulting in the occurrence of liposis in the cervical muscles. In addition, the cytochrome c oxidase activity was also retarded leading to the ATP formation failure. Regarding the preventive studies, we used the four nutraeutics, i.e. folic acid (FA), glutathione (GSH), N-acetyl-cysteine (NAC), and vitamin E (Vit E). Results indicated all the adverse effects exhibited by GA were totally alleviated, no difference of outcomes was found between the timings of administration, i.e. co-administration during the embryonic stage or by tube-feeding after hatched. Conclusively, GA at normally prescribed dosages could exhibit teratogenicity to embryos. The symptoms may involve abnormal angiogenesis, oxidative stress, hemolysis, myoinflammation, necrosis, blocking of cytochrome c oxidase and liposis in cervical muscles. Folic acid (FA), glutathione (GSH), N-acetyl-cysteine (NAC), and vitamin E (Vit E) were all found effective regarding both the prevention and rehabilitation. Suggestively, in prescribing GA for clinical uses, the co-prescription of these four nutraceutics are highly recommended. To our believe, the results presented in this report would be a valuable reference in any cuircumstane when GA is to be assigned for any clinical therapy.
|
|---|
