Neuroprotective potential of saroglitazar in 6‐OHDA induced Parkinson's disease in rats

Abstract

AbstractParkinson's disease (PD) is a neurodegenerative disorder that affects 2%–3% of the population worldwide. Clinical presentation of PD includes motor and non‐motor symptoms. The interplay between pathogenic factors such as increased oxidative stress, neuroinflammation, mitochondrial dysfunction and apoptosis are responsible for neurodegeneration in PD. Intrastriatal administration of 6‐hydroxy dopamine (6‐OHDA) in rat brain provoked oxidative and nitrosative stress by decreasing endogenous antioxidants such as superoxide dismutase, catalase, glutathione, glutathione peroxidase and glutathione reductase. Consequently, interleukin‐6, tumour necrosis‐α, interferon‐γ and cyclooxygenase‐2 mediated neuroinflammation leads to mitochondrial dysfunction, involving inhibition of complex‐II and IV activities, followed by apoptosis and degeneration of striatal dopaminergic neurons. Degeneration of dopaminergic neurons resulted in reduced dopamine turnover, consequently induced behavioural abnormalities in rats. Activation of peroxisome proliferator‐activated receptors (PPARs) have protective role in PD by modulating response of antioxidant enzymes, neuroinflammation and apoptosis in various animal models of PD. Saroglitazar (SG) being dual PPAR‐α/γ agonist activates both PPAR‐α and PPAR‐γ receptors and provide neuroprotection by reducing oxidative stress, neuroinflammation, mitochondrial dysfunction and apoptosis of dopaminergic cells in 6‐OHDA induced PD in rats. Thereby, SG restored striatal histopathological damage and dopamine concentration in rat striatum, and behavioural alterations in rats. Thus, SG proved neuroprotective effects in rat model of PD. Potential benefits of SG in rat model of PD advocates to consider it for further preclinical and clinical evaluation.