Neuroprotective Effects Of Iron Chelator Desferal On Dopaminergic Neurons In The Substantia Nigra Of Rats

Parkinson's disease (PD) is a progressive neurodegenerative disorder associated with the loss of dopamine (DA) neurons in the substantia nigra (SN). The increased level of brain tissue iron has been implicated as a major generator of reactive oxygen species which are capable of damaging biological molecules such as lipids, carbohydrates, proteins and nucleic acids. The previous studies of our group suggest that high iron in brain has close relationship with PD. Researchers try to seek new preventive measures for PD at different points of view and etiologies, and iron-chelating strategies have been at the focus of attention. The aim of this study is to investigate the possibility of iron chelator desferal to prevent DA neurons in SN from the degeneration induced by iron overload and neurotoxin 6-OHDA. In iron dextran overloaded rats and desferal treated rats, using fast cyclic voltammetry (FCV), TH immuohistochemistry , Perls' iron staining , high performance liquid chromatography-electrical chemical detection (HPLC-ECD), semi-quantitive reverse transcriptase-polymerase chain reaction (RT-PCR), we investigated the release of DA in the striatum (Str) of rats, the contents of DA and its metabolites dihydroxy-phenylacetic acid (DOPAC) and homovanillic (HVA) in the Str, the survival of DA neurons and the changes of iron in the SN. In 6-OHDA PD rats and desferal treated rats, we observed the expression of TH and dopamine transporter (DAT) gene in the SN and examined rotational behavior induced by apomorphine (APO) of rats The results were as follows:1. For the iron overload group, the DA release in the Str was apparently lower compared with the normal group (P<0.01). When treated with desferal, DA release was much higher compared with the iron overloaded group (P<0.05).2 The content of DA and its metabolites DOPAC , HVA of the iron overloaded group decreased significantly compared with the normal group (P<0.05). When treated with desferal, the content of DA and its metabolites was much higher compared with the iron overloaded group (P<0.01).3. In the iron overloaded group, the SN showed an apparent increase in iron staining While treated with desferal, the number of iron staining cells decreased compare to the iron overloaded group (P<0.01).4 In the iron overloaded group, the SN exhibited a marked decreased in TH immunoreactive cells While treated with desferal, there were much more TH immunoreactive cells in the SN compare to the iron overloaded group (P<0.01).