Effect Of Caffeic Acid On Brain Damage Induced By Chronic Aluminum Overload In Rats And Its Mechanism

Objective: To investigate the effect of caffeic acid on brain damage and the protective mechanism in chronic aluminum overload rats.Methods: The brain injury model of rats were established via intragastric administration of aluminum gluconate (element aluminum 200 mg·kg-1) once a day, 5 d a week for 20 weeks. The 5-LO inhibitor caffeic acid (30 mg·kg-1 and 10 mg·kg-1) was intragastrically administered 1 h after aluminum administration. Pathomorphological changes of hippocampal neuron and the spatial learning and memory function were observed. The MAO-B, AchE and SOD activities, and the MDA contents of brain tissue in rats were measured. The mRNA and protein expression of 5-LO and COX-2 in rat hippocampi were detected by methods of RT-PCR and western-blotting, respectively. The changes of Aβ, APP, ChAT and TH expression in rat brain were also detected by immunohistochemistry method. The level of metal ion in rat brain was determined by plasma atomic emission spectroscopy.Results: Chronic aluminum overload could markedly induce spatial learning and memory function impairment, and hippocampal neuronal injury in rats. The MAO-B, AchE activities and the MDA content significantly increased, while SOD activities significantly decreased in chronic aluminum overload rats. After aluminum administration, the mRNA and protein expression of 5-LO and COX-2 in rat hippocampi remarkably increased. The expression of Aβand APP obviously increased, whiles the expression TH and ChAT significantly decreased. The level of metal ion in rat brain was remarkably increased.The administration of the caffeic acid could significantly prevent rats from learning and memory function impairment and hippocampal neuronal death, and blunted the decrease of SOD activities and the increase of MDA content induced by chronic aluminum overload in rats. Caffeic acid also obviously decreased the MAO-B and AchE activities of chronic aluminum overload rats. The mRNA and protein expression of 5-LO and COX-2 in hippocampi was down regulated in chronic aluminum overload rats. Caffeic acid administration significantly increased the hippocampal neuronal ChAT and TH expression, and significantly decreased the hippocampal neuronal Aβand APP expression. Caffeic acid also decreased the level of metal ion in chronic aluminum overload rat brainConclusions: These experimental results indicate that caffeic acid has a protective effect on chronic brain injury induced by aluminum overload in rats. The inhibition of 5-LO activity, further the antiinflamation and antioxidatve stress are involved in the cerebroprotective mechanisms of caffeic acid.