The Impact of Recombinant Human Erythropoietin Treatment on Motor Impairment in Rotenone-Induced Parkinsonism in Rats

Abstract

Background: Parkinson's disease is a neurodegenerative disease mainly characterized by loss of dopaminergic neurons in the substantia nigra pars compacta and their terminals in the striatum. The development of neuroprotective drugs that slow or delay neurodegeneration became of a considerable interest. In numerous animal models, exogenously administered EPO exhibits neuroprotective effects. Aim: The current research investigated the impact of administration of recombinant human EPO (rhEPO) in rotenone parkinsonian rats. Materials and Methods: Thirty two adult male albino Sprague-Dawly rats were equally and randomly divided into four groups; group 1 the vehicle-treated group, group 2 rotenone-treated group, group 3 treated with rotenone in addition to intranasal rhEPO and group 4 treated with rotenone in addition to intraperitoneal rhEPO. The motor performance of the rats was evaluated. Malondialdehyde and reduced glutathione were assayed. Blood indices were measured. Histopathology of the substantia nigra was also done. Results: Results showed that rotenone-treated rats exhibited significant impairment of motor coordination and marked degeneration of substantia nigra neurons was observed. Both intranasal and intraperitoneal rhEPO treatment improved the motor deficit and significantly increased the number of neurons in the SNpc. intraperitoneal rhEPO significantly increased lipid peroxide and significantly affected blood indices. Conclusion: Our findings suggest that, EPO may have neuroprotective effect in PD. Systemic rhEPO neuroprotective effects may be attenuated by its adverse effects such as increase of OS in the vascular system and stimulation of erythropoiesis. Small doses of intranasal EPO may be sufficient to produce neuroprotection without affecting erythropoiesis and further researches are required to address the mechanisms of neuroprotective effects of EPO.