The Mechanism Of Neurotoxicity After Aluminum Exposure On Rat And The Protective Effect Of Polyphenol Extract Against Aluminum-induced Biotoxicity

Aluminum is the most widely distributed metal in the environment and is extensively used in modern daily life.There is no known physiological role for aluminum within the body and this metal may produce adverse physiological effects on central nervous system,liver and blood system.The mechanisms underlying aluminum exposure are still controversial.The present study investigated the mechanism of neurotoxicity after aluminum exposure on rat and the potential protective effect of polyphenol extract against aluminum-induced biotoxicity.A novel post-electrophoresis staining procedure relied on the reaction of aluminium(Al)with 8-hydroxyquinoline(8-HQ)is performed to achieve visualization of Al binding proteins in rat brain.Proteins are separated under non-reducing conditions using native-PAGE(polyacrylamide gel electrophoresis)and stained using a standard protocol involving Al salts and 8-HQ.The protein-Al-HQ complex undergo an ultraviolet light to produce fluorescence in the visible range so that the protein bands can be visualized.After that,the two fluorescent protein bands were identified as CK-B and 14-3-3 ?,respectively,as demonstrated by LC-MS/MS.Based on it,rats were treated orally with aluminum chloride(AlCl3),and CK activity in their brain homogenates was then assayed.Results showed that this in vivo treatment reduced the activity of the enzyme.An inactivating effect was also observed,when the AlCl3 solution was added directly to rat brain homogenates.In addition,a strong inhibitory effect on the interaction between Tau and 14-3-3 C has been observed in the presence of treatment with Al in vitro and this inhibitory effect was dependent on the concentration of Al.This finding will be useful to gain an insight into the role of Al in neurological disorders relation to the ability of Al to bind to CK-B or 14-3-3?,and to alter the normal function of the two proteins.Our study showed that jujube phenolics can reduce aluminum bioicity in rats.Treatment with aluminum chloride could cause a significant oxidative damage,including a significant increase in hematological parameters,MDA level and decreases in glutathione-S-transferase and SOD activities in brain of the rats,the study showed that gavage with JPFP or JPBP could remarkably alleviate the toxic responses of the rats to aluminum chloride.This study was aimed to evaluate the preventive effect of the apple(Ralls)polyphenol extract(APE)against aluminum(Al)toxicity in adult rat.Control,Al-treated(171.8 mg Al/kg(day add in the formulated diet for 10 weeks)and APE+Al(Al-treatment as previously plus 200 mg APE/kg/day diluted in the drinking water for 10 weeks),groups of APE per se were used.The behavioral studies to evaluate memory(Morris water maze and step-down inhibitory avoidance task)were done.As compared to control,Al intake caused memory impairment,significant decrease of AChE,CK,SOD,catalase activity and the rate of ATP synthesis,increase the level of MDA and ?-amyloid 42 in brain;the activities of SOD and CAT,the levels of glutathione and ATP synthesis were decreased;while the activities of transaminases in serum,the levels of Al content and ATP hydrolysis were increased significantly in the liver of Al treated group.Furthermore,the abnormal changes in histological structure were observed.Chronic administration of APE significantly improved memory retention in both tasks,attenuated oxidative damage and Al concentration in Al treated rats.APE has neuroprotective effects and hepatoprotective effect against Al-induced cognitive dysfunction and oxidative damage.The stability constants for the complexes between the chlorogenic acid+Al(?)were determined log K=10.51).The mole ratio of metal to ligand was kept at 1:1 for chlorogenic acid to reach the maximum coordination of the ligand.We performed an in vitro studies(incubating rat serum protein in the absence or presence of a series of phenolic acids)and analyzed the affinity of Al(?)for serum albumin using 8-HQ staining method.The results suggested that phenolic acids exerted a strong inhibitory effect on the interaction between Al and serum albumin and this inhibitory effect was dependent on the concentration of phenolic acids.As compared to the DPPH radical scavenging activity of the phenolic acids,chelation and antioxidation were two different protective pathway of phenolic acids against Al induced biotoxicity.Our study also showed that chlorogenic acid can stimulated the excretion of Al in rats.According to the these,it concluded that chelation was the important mechanism of polyphenols reducing the biotoxicity induced by Al.