Evaluation of the antiparkinsonism and neuroprotective effects of hydrogen sulfide in acute 6-hydroxydopamine-induced animal model of Parkinson’s disease: behavioral, histological and biochemical studies

Abstract

Introduction: Studies have shown that hydrogen sulfide (H₂S), a gaseous neurotransmitter, has neuroprotective effect. Here, we evaluated the neuroprotective activity of H₂S in acute 6-hydroxydopamine (6-OHDA) animal model of Parkinson’s disease (PD).

Methods: 6-OHDA was injected through stereotaxic surgery into medial forebrain bundle (MFB) of the right hemisphere to induce severe and fast degeneration in dopaminergic neurons of substantia nigra (SN). NaHS, as donor of H₂S, was daily injected at doses of 3 and 5.6 mg/kg for seven days starting a few hours before the surgery. A series of behavioral tests were carried out and then, remaining tyrosine hydroxylase (TH)-positive neurons in substantia nigra pars compacta (SNc) was determined using immunohistfluresance staining. Striatal dopamine level and oxidative stress markers were also measured in the brain homogenates using immunosorbent assay kits.

Results: NaHS attenuated apomorphine-induced rotational activity, decreased bias swings in elevated body swing test and increased falling time in rotarod test. Our histological and biochemical data demonstrated that NaHS treatment increases the survival of TH-positive neurons in SNc and also reduces the decreasing effect of 6-OHDA on striatal dopamine level. NaHS also reduced 6-OHDA-induced malondialdehyde overproduction but had no effect on the superoxide dismutase and glutathione peroxidase activity.

Conclusion: Our results show that H₂S produces significant antiparkinsonism and neuroprotective effects against 6-OHDA neurotoxicity. Since injection of 6-OHDA into MFB produces severe lesion in SN dopaminergic neurons similar to this lesion in the onset of PD in human being, our data recommend H₂S as potential therapeutic target for treatment of this disease.

Keywords:

• Parkinson’s disease
• MFB
• NaHS
• TH-positive neurons
• striatal dopamine level
• malondialdehyde

Acknowledgment

We appreciate Mrs. Ayda Faraji for her assistance in stereotaxic surgery and also Ms. Zare for her assistance in immunohistofluresance experiments.