Parkinsonism-like Disease Induced by Rotenone in Rats: Treatment Role of Curcumin, Dopamine Agonist and Adenosine A2A Receptor Antagonist

Abstract

Background: Parkinsonism is a neurodegenerative disorder that affects elderly people worldwide.

Methods: Curcumin, adenosine A_2AR antagonist (ZM241385) and Sinemet^® (L-dopa) were evaluated against Parkinson's disease (PD) induced by rotenone in rats, and the findings were compared to our previous study on mice model.

Results: Rats injected with rotenone showed severe alterations in adenosine A_2A receptor gene expression, oxidative stress markers, inflammatory mediator, energetic indices, apoptotic marker and DNA fragmentation levels as compared to the control group. Treatments with curcumin, ZM241385, and Sinemet^® restored all the selected parameters. The brain histopathological features of cerebellum regions confirmed our results. By comparing our results with the previous results on mice, we noticed that mice respond to rotenone toxicity and treatments more than rats with regards to behavioral observation, A_2AR gene expression, neurotransmitter levels, inflammatory mediator and apoptotic markers, while rats showed higher response to treatments regarding oxidative stress and energetic indices.

Conclusion: Curcumin succeeded in attenuating the severe effects of Parkinson's disease in the rat model and can be considered as a potential dietary supplement. Adenosine A_2AR antagonist has almost the same pattern of improvement as Sinemet^® and may be considered as a promising therapy against PD. To compare the role of animal species in response to PD symptoms and treatments, our previous report on mice explored the response of mice to rotenone toxicity in comparison with rats, where rats have shown a higher response to treatments. Therefore, no animal model can perfectly recapitulate all the pathologies of PD.

Keywords: A2AR antagonist; Curcumin; histopathological features.; parkinsonism; rats; rotenone.