Hydroxychloroquine attenuated motor impairment and oxidative stress in a rat 6-hydroxydopamine model of Parkinson’s disease

Abstract

Purpose

Parkinson’s disease (PD) is associated with the destruction of dopaminergic neurons in the substantia nigra (SN). Hydroxychloroquine (HCQ) has the capability to cross the blood–brain barrier and promote a neuroprotective potential. This study evaluated the effects of HCQ on the 6-hydroxydopamine (6-OHDA)-induced PD model in rats.

Methods

Wistar rats were randomly divided into sham, PD, PD + levodopa and PD + HCQ groups. The PD model was induced by a stereotactic administration of 6-OHDA into the left SN pars compacta (SNpc) and confirmed by rotation and the Murprogo’s tests. HCQ (100 mg/kg, p.o.) and levodopa (12 mg/kg, p.o.) were administered once a day for 21 days. Three weeks after surgery, the behavioral tests were performed. Brain lipid peroxidation index (MDA), glutathione peroxidase activity (GPx), total antioxidant capacity (TAC) levels and α-synuclein protein expression in the SN were also measured.

Results

The behavioral tests demonstrated that induction of PD increased the muscle rigidity and the number of rotations, which were reversed by HCQ treatment. Also, induction of PD was associated with an increase in α-synuclein protein levels and MDA and decreased TAC levels and GPx activity. However, HCQ decreased α-synuclein and MDA levels while increased TAC levels and GPx activity. In addition, histopathological data showed that HCQ protects dopaminergic neurons against 6-OHDA-induced toxicity.

Conclusion

According to the results, HCQ has a beneficial effect in improving PD-related pathophysiology, in part, by mitigating oxidative stress and protecting the dopaminergic neurons in the SN.

Keywords:

• Parkinson’s disease
• hydroxychloroquine
• levodopa
• 6-OHDA
• oxidative stress

Author contributions

GM and SZA conceived and designed research. SZA, MAN and FF conducted experiments. SSE and DM analyzed data. SZA and FF wrote the manuscript. All authors read and approved the manuscript and all data were generated in-house and that no paper mill was used.

Disclosure statement

The authors have no relevant financial or non-financial interests to disclose.

Data availability statement

Data available on request from authors

Additional information

Funding

The research protocol was approved & Supported by Student Research Committee, Tabriz University of Medical Sciences (grant number: 67457). Author Seyed Zanyar Athari has received research support from Student Research Committee.