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Effect of heme oxygenase-1 on neuro-degeneration induced by aluminum overloading

YUAN Ye,GUO Jian-Zeng,YANG Jun-Qing,ZHOU Qi-XinDepartment of Pharmacology,College of Pharmacy,Chongqing Medical University,Chongqing 400016,China  
AIM: To investigate the effect of heme oxygenase-1(HO-1) on neurodegeneration induced by aluminum overloading(AO).METHODS: Seventy-five male NIH mice weighing 24-26 g were divided into control,aluminum chloride low dosage group(3.75 mg/d,LD) and high dosage group(7.50 mg/d,HD),which were intracerebraventricularly injected with 3 μL per mouse of artificial cerebrospinal fluid,1.25 g/L aluminum chloride solution and 2.50 g/L aluminum chloride solution,respectively once a day for 5 d to build the neurodegenerative model.The effect of HO-1 on neurodegeneration induced by AO was eva-luated by parameters including HO activity,HO-1 expression,content of malonaldehyde(MDA),levels of metal ions,and pathomorphological changes of hippocampi.RESULTS: The layer of CA1 pyramidal cells in both AO groups became thinner with pyknotic nuclei than control.The significant increases of HO-1 expression(LD 0.24±0.01,HD 0.33±0.01) and level of iron [(LD(31.34±2.85) mg/g,HD(54.01±2.31) mg/g)] with elevation of MDA level,HO activity and aluminum level were observed in both AO groups,compared with control group [HO-1 0.10±0.01,iron(22.54±4.48) mg/g,P0.05].CONCLUSION: Neurodegeneration induced by AO may involve in the up-regulation of HO-1,which raises the level of iron from degradation of the heme.
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