Abstract
•Parkinson’s disease (PD) is a worldwide neurodegenerative disorder.•Although, drawbacks of l-dopa, it is still the cornerstone medication for PD.•Filgrastim is one of hematopoietic growth factors, proved to be neurotrophic.•Recently, filgrastim showed antioxidant, anti-apoptotic & immunomodulating effects.•Filgrastim co-therapy ameliorated Parkinsonism l-dopa therapy’s drawbacks.
l-dopa is still the cornerstone symptomatic medication for Parkinson disease (PD), although it cannot stop the neurodegenerative process progression or even aggravate it. Filgrastim (G-CSF) is a hematopoietic growth factor, exhibited neurotrophic, antioxidant, anti-apoptotic, immunomodulating and neuroprotective potentialities. The present study assessed the possible modulating potentialities of filgrastim on l-dopa treatment’s drawbacks in a mouse model of PD. Male BALB/c mice received 30 mg/kg/day rotenone suspended in 0.25 ml 0.5% CMC in PBS for 28 days orally from day 1st until the day 28th of the experiment for induction of PD. Since day 29th till day 43rd, mice treated with either 10 mg/kg/day l-dopa and 2.5 mg/kg/day carbidopa suspended in 0.25 ml 0.5% CMC in PBS orally, 50 μg/kg/day filgrastim in 0.1 ml 5% dextrose SC or a combination of both. Filgrastim, in the present study, able to alleviate the l-dopa therapy’s drawbacks in PD that revealed by the restoration of the exhausted nigrostriatal GSH level, and the reduction of the elevated nigrostriatal MDA, NO and TNF-α levels that deteriorated by l-dopa therapy. Moreover, the co-therapy of filgrastim with l-dopa, considerably potentiated the deteriorated mice’s working memory, and abrogated the nigrostriatal histopathological changes and caspase-3 immunohistochemical expression, failed to improve by l-dopa therapy. Furthermore, the filgrastim co-therapy with l-dopa demonstrated a remarkable improvement in the nigrostriatal dopamine level, and repression of rotenone-induced descent latency prolongation, as well as, stride length reduction than each alone. Therefore, filgrastim is promising, as a disease-modifying therapy, in amelioration of l-dopa therapy’s drawbacks in PD.