Kolaviron protects against nigrostriatal degeneration and gut oxidative damage in a stereotaxic rotenone model of Parkin
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ORIGINAL INVESTIGATION
Kolaviron protects against nigrostriatal degeneration and gut oxidative damage in a stereotaxic rotenone model of Parkinson’s disease Ebenezer O. Farombi 1 & Ifeoluwa O. Awogbindin 1 & Precious D. Olorunkalu 1 & Emmanuel Ogbuewu 1 & Bisola F. Oyetunde 1 & Alberta E. Agedah 1 & Philip A. Adeniyi 2 Received: 7 April 2020 / Accepted: 29 June 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract The asymptomatic and clinical stages of Parkinson’s disease (PD) are associated with comorbid non-motor symptoms including gastrointestinal (GI) dysfunction. Although the neuroprotective and gastroprotective roles of kolaviron (KV) have been reported independently, whether KV-mediated GI-protective capacity could be beneficial in PD is unknown. We therefore investigated the modulatory effects of KV on the loss of dopaminergic neurons, locomotor abnormalities, and ileal oxidative damage when rats are lesioned in the nigrostriatal pathway. KV treatment markedly suppressed the behavioral deficit and apomorphine-induced rotations associated with rotenone lesioning. KV attenuated the loss of nigrostriatal dopaminergic neurons and perturbations in the striatal glucose-regulated protein (GRP78) and X-box binding protein 1 (XBP1) levels. Ileal epithelial injury following stereotaxic rotenone infusion was associated with oxidative stress and marked inhibition of acetylcholine esterase activity and reduced expression of occludin in the crypt and villi. While KV treatment attenuated the redox imbalance in the gut and enhanced occludin immunoreactivity, acetylcholinesterase activity was not affected. Our data demonstrate ileal oxidative damage as a characteristic non-motor gut dysfunction in PD while showing the potential dual efficacy of KV in the attenuation of both neural defects and gut abnormalities associated with PD. Keywords Parkinson’s disease . Gut oxidative damage . Stereotaxic rotenone model . Kolaviron . Neuroprotection
Introduction Parkinson’s disease (PD) is a complex, multifactorial neurodegenerative disease characterized by continuous degeneration of dopaminergic (DA) nigrostriatal neurons and the pathologic intraneuronal cytoplasmic protein inclusions known as Lewy body, which primarily consist of α-synuclein (Braak et al. 2003; Jiang and Dickson 2018). PD affects individuals around the age of 60 years with increasing risk at older age (Tysnes and Storstein 2017). In Nigeria, 2.75% of individuals
* Ebenezer O. Farombi [email protected] 1
Drug Metabolism and Molecular Toxicology Research Laboratories, Department of Biochemistry, University of Ibadan, Ibadan, Nigeria
2
Cell Biology and Neurotoxicity Unit, Department of Anatomy, College of Medicine and Health Sciences, Afe Babalola University, Ado Ekiti, Ekiti State, Nigeria
who are 65 years and above are at risk of developing late-onset PD (Oluwole et al. 2019). The cardinal features of PDassociated motor deficits are muscular rigidity, resting tremor, bradykinesia, abnormal shuffling of gaits, and postural instab
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