Objective: This study examined the effect of pretreatment with All-trans-retinoic Acid (ATRA) on the 6-hydroxydopamine-induced Parkinsonism in Wistar rats in order to find out whether ATRA could attenuate oxidative stress, behavioural and structural abnormalities in an experimental model of PD in rat.

Background: Parkinson’s disease refers to a progressive neurodegenerative disorder involving degeneration of dopaminergic neurons particularly in substantia nigra. The loss of dopaminergic cells results in complex motor syndrome. One of the hypothesis in pathogenesis of PD is oxidative stress via NADPH-dependent oxidases. ATRA have been reported to increase oxidative burden.

Methods: 48 male wistar rats were divided into four groups: (1) sham, normal saline was injected in the left SNC (substantia nigra pars compacta) , (2) 6-OHDA, 6-hydroxydopamine was injected into left SNC, (3) 6-OHDA+ATRA (10 mg/kg, p.o), (4) 6-OHDA+ATRA (20 mg/kg, p.o). ATRA were given rats daily from eight dayes before the surgery to a day after. At the end of the experiment, oxidative stress markers, apomorphine-induced rotational asymmetry were measured and the number of Nissl-stained and tyrosine-hydroxylase (TH)-positive neurons on the left side of the substantia nigra after 2 weeks were counted.

Results: ATRA administration could attenuate the rotational behavior and also restore malondialdehyde and nitrite content and catalase activity in lesioned rats pretreated with ATRA and protect the neurons of SNC against 6-OHDA toxicity in comparison with the group which received only neurotoxin.

Conclusions: In conclusion, the results of the present study suggest that ATRA administration has a protective effect against 6-OHDA toxicity and may be useful for as an adjuvant therapy for management of PD at its early stages.

References: Lee, H.-P., Hyun-Pil, L., Gemma, C., Xiongwei, Z., Hyoung-gon, L., George, P., … Alan, L. (2009). All- trans retinoic acid as a novel therapeutic strategy for Alzheimer’s disease. Expert Review of Neurotherapeutics, 9(11), 1615–1621. Jalali-Nadoushan, M., Mohammadreza, J.-N., & Mehrdad, R. (2013). Alpha-lipoic acid protects against 6-hydroxydopamine-induced neurotoxicity in a rat model of hemi-parkinsonism. Brain Research, 1505, 68–74.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/all-trans-retinoic-acid-pretreatment-exhibits-neuroprotective-effect-against-6-hydroxydopamine-induced-hemi-parkinsonian-rats/