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Ursodeoxycholic Acid Ameliorates Apoptotic Cascade in the Rotenone Model of Parkinson’s Disease: Modulation of Mitochondrial Perturbations

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Abstract

The recent emergence of ursodeoxycholic acid (UDCA) as a contender in modifying neurotoxicity in human dopaminergic cells as well as its recognized anti-apoptotic and anti-inflammatory potentials in various hepatic pathologies raised impetus in investigating its anti-parkinsonian effect in rat rotenone model. UDCA prominently improved motor performance in the open field test and halted the decline in the striatal dopamine content. Meanwhile, it improved mitochondrial function as verified by elevation of ATP associated with preservation of mitochondrial integrity as portrayed in the electron microscope examination. In addition, through its anti-inflammatory potential, UDCA reduced the rotenone-induced nuclear factor-κB expression and tumor necrosis factor alpha level. Furthermore, UDCA amended alterations in Bax and Bcl-2 and reduced the activities of caspase-8, caspase-9, and caspase-3, indicating that it suppressed rotenone-induced apoptosis via modulating both intrinsic and extrinsic pathways. In conclusion, UDCA can be introduced as a novel approach for the management of Parkinson’s disease via anti-apoptotic and anti-inflammatory mechanisms. These effects are probably linked to dopamine synthesis and mitochondrial regulation.

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Acknowledgments

The authors are grateful to Dr. Manal I. Salman, professor of Pathology, Faculty of Medicine, Ain Shams University, and vice director of Electron Microscopy Unit at Ain Shams University Specialized Hospital, for her efforts in the electron microscopic examinations.

Conflict of Interest

The authors declare that there are no conflicts of interest to disclose.

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  1. Marwa M. Safar

    Present address: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt

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  1. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt

    Noha F. Abdelkader & Hesham A. Salem

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Abdelkader, N.F., Safar, M.M. & Salem, H.A. Ursodeoxycholic Acid Ameliorates Apoptotic Cascade in the Rotenone Model of Parkinson’s Disease: Modulation of Mitochondrial Perturbations. Mol Neurobiol 53, 810–817 (2016). https://doi.org/10.1007/s12035-014-9043-8

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