Neurotoxicity Research

, Volume 35, Issue 3, pp 542–562 | Cite as

Rebamipide Mitigates Impairments in Mitochondrial Function and Bioenergetics with α-Synuclein Pathology in 6-OHDA-Induced Hemiparkinson’s Model in Rats

  • Akanksha Mishra
  • Sairam KrishnamurthyEmail author
Original Article


Parkinson’s disease (PD) is one of the widely reported neurodegenerative disorders affecting more than ten million people worldwide. Due to therapeutic limitations and several adverse effects associated with currently used drugs, it is crucial to search for safe and effective options for treatment of PD. Oxidative stress, mitochondrial dysfunction, α-synuclein oligomeric aggregates, and glucocerebrosidase (GCase) deficiency are involved in PD pathogenesis. Rebamipide, an anti-ulcer drug, is a proven free-radical scavenger and antioxidant. The drug has shown neuroprotective effects in cultured SH-SY5Y cells. Therefore, we investigated the pharmacological effect of rebamipide in 6-hydroxydopamine (6-OHDA)-induced experimental PD model. Rebamipide was given to adult male albino rats of Charles-Foster strain in 20, 40, and 80 mg/kg (R-20, R-40, and R-80) oral dose twice daily for 24 days (day 4 to day 27) after 6-OHDA intrastriatal injection. The drug inhibited 6-OHDA-induced motor deficits and nigral α-synuclein aggregates in dose-dependent manner. R-40 and R-80 dose dependently increased striatal mitochondrial complex I, II, IV, and V activities; mitochondrial bioenergetics; and nigral GCase activity. 6-OHDA-induced lipid peroxidation was decreased. Highest dose (R-80) also decreased apoptotic proteins and upregulated striatal dopamine concentration in 6-OHDA-induced hemiparkinson’s rat model. Therefore, the anti-PD effect of rebamipide may involve stabilization of mitochondrial bioenergetics, enhancement of GCase enzymatic activity as well as decreased oxidative stress with α-synuclein pathology, and apoptosis in 6-OHDA-induced hemiparkinson’s rat model. Hence, preclinical evidence indicates rebamipide to be a potential drug for management of PD.


Rebamipide Mitochondrial bioenergetics Oxidative stress Parkinson’s disease α-Synuclein Glucocerebrosidase 









amyloid-β 1–42


adenosine diphosphate


adenosine triphosphate




bovine serum albumin




central nervous system






deoxyribonucleic acid


3,4-dihydroxyphenylacetic acid


electrochemical detector


ethylene glycol-bis (β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid


enzyme-linked immunosorbent assay


endoplasmic reticulum


electron transport chain


flavin adenine dinucleotide


carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone








Hydrogen ion


hydrogen peroxide


4-(2-hydroxyethyl)-1-piperazine ethanesulfonic acid


high-performance liquid chromatography


homovanillic acid


inducible nitric oxide synthase




potassium phosphate monobasic anhydrous


lipid peroxide


monoamine oxidase B






magnesium chloride










mitochondrial membrane potential








nicotinamide adenine dinucleotide (oxidized)


nicotinamide adenine dinucleotide (reduced)


nitroblue tetrazolium




National Institutes of Health Guide for the Care and Use of Laboratory Animals






open field test


Parkinson’s disease




inorganic phosphate


per os


rebamipide 20 mg/kg


rebamipide 40 mg/kg


rebamipide 80 mg/kg


respiratory control ratio


ribonucleic acid


reactive oxygen species




standard deviation


sodium dodecyl sulfate polyacrylamide gel electrophoresis




superoxide dismutase


substantia nigra pars compacta


thiobarbituric acid reactive substances



The authors wish to acknowledge Akums Drugs & Pharmaceuticals Ltd., New Delhi, India for providing rebamipide (active pharmaceutical ingredient) as gift sample. This work was supported by the teaching assistantship to Akanksha Mishra from Indian Institute of Technology (Banaras Hindu University), Varanasi-221005, U.P., India.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All the procedures performed in the study were in accordance with the ethical standards of the Institutional animal ethical committee, Banaras Hindu University (Dean/2016/CAEC/33). The experiments were performed according to the principles of National Institutes of Health Guide for the Care and Use of Laboratory Animals (NIH Publications No. 8023, revised 1978) guidelines. The article does not contain any studies with human participants performed by any of the authors.


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Authors and Affiliations

  1. 1.Neurotherapeutics Laboratory, Department of Pharmaceutical Engineering & TechnologyIndian Institute of Technology (Banaras Hindu University)VaranasiIndia

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