Research Of The Pharmacodynamics Of ZnFDP For Senile Dementia

Objective: The pharmacodynamics of zinc fructose diphosphate (ZnFDP) on the newborn rat hippocampal neurons in vitro and the senile dementia model mice in vivo were studied. Methods: (1) The newborn rat hippocampal neurons were cultured with 2.5 12.5 125 u g ml-1 ZnFDP. Zinc sulfate and piracetam were selected as the positive control agents. The convert phase microscope was used to analyse the number and the length of neurites, as well as the maximum diameter of hippocampal neurons soma. The survival neurons count and lactate dehydrogenase (LDH) assay were carried out to investigate the effect of ZnFDP on the growth and development of neurons in different culture time. (2) The LD50 for mouse (po) was calculated with the Bliss method. (3) The NIH mice were treated with D-galactose (120 mg -kg-1 -d-1, ip, 60d) and NaNO2 (90 mg -kg-1 -d-1, ip,60d) to make thesenile dementia animal model. The three therapy groups were treated with ZnFDP 142 284 568mg kg-1 d-1 (po,14d) respectively since d47. The piracetam positive control group was fed with piracetam(500 mg kg-1 d-1 po,14d) since d47. The mouse water-maze test, the analysis of protein content and AchE, SOD, ATPase activities in brains, as well as the pathological observation of the hippocampus and cerebral cortex were carried out to evaluate the effect of ZnFDP on the senile dementia model mice.Results: (1) The results showed that 2.5 u g ml-1 ZnFDP didn't have any effects on the cultured newborn rat hippocampal neurons. 12. 5 u g ml-1 ZnFDP could promote the growth and development of neurons. 125 u g ml-1 ZnFDP, however, inhibited obviously the growth of neurons. (2) The LDso (mouse, po) of ZnFDP is 5.67g kg-1. It is low toxicity and safe. (3) The tests in vivo showed that by oral administration with ZnFDP(568 mg kg-1 d,4d, the capacity of learning and memory of the senile dementia model micewas improved, by oral administration with 142 284 568 mg kg-1 d-1 Zn FDP for 14 days, the activities of AchE and SOD in brain reached the normal levels. But the senile dementia model mice could not recover from the serious pathological lesion in their brains.Conclusions: This study suggested that the suitable dose of ZnFDP can promote the growth and development of hippocampal neurons, meliorate the learning and memory deficiency in the senile dementia model mice and sustain the normal levels of AchE and SOD in brain. ZnFDP deserves continual research for its nootropic effect and anti-cholinesterase and scavenging oxygen free radical effects in CNS.