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Journal of Neurorestoratology  2014, Vol. 2 Issue (1): 47-64    doi: 10.2147/JN.S50114
OriginNal Rresearch     
Cerebrolysin protects against rotenone-induced oxidative stress and neurodegeneration
Omar ME Abdel-Salam1, Nadia A Mohammed2, Eman R Youness2, Yasser A Khadrawy3, Enayat A Omara4, Amany A Sleem5
1Department of Toxicology and Narcotics,;
2Department of Medical Biochemistry,;
3Department of Physiology,;
4Department of Pathology,;
5Department of Pharmacology, National Research Centre, Dokki, Cairo, Egypt
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Abstract  We investigated the effect of cerebrolysin, a peptide mixture used for promoting memory and recovery from cerebral stroke, on the development of oxidative stress and nigrostriatal cell injury induced by rotenone administration in rats. Rotenone 1.5 mg/kg was given subcutaneously three times weekly either alone or in combination with cerebrolysin at 21.5, 43, or 86 mg/kg. Rats were euthanized 14 days after starting the rotenone injection. Lipid peroxidation (malondialdehyde), reduced glutathione (GSH), nitric oxide (nitrite) concentrations, paraoxonase 1 (PON1), and acetylcholinesterase (AChE) activities - as well as the monocyte chemoattractant protein-1 (MCP-1) and the antiapoptotic protein Bcl-2 - were measured in the brain. Histopathology, tyrosine hydroxylase, inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), and cleaved caspase-3 immunohistochemistry were also performed. Rotenone caused a significantly elevated oxidative stress and proinflammatory response in the different brain regions. Malondialdehyde and nitric oxide concentrations were significantly increased, while GSH markedly decreased in the cerebral cortex, striatum, hippocampus, and in the rest of the brain. PON1 and AChE activities significantly decreased with respect to the control levels after rotenone application. Striatal Bcl-2 was significantly decreased while MCP-1 increased following rotenone injection. Rotenone caused prominent iNOS, TNF-α, and caspase-3 immunostaining in the striatum and resulted in markedly decreased tyrosine hydroxylase immunoreactivity in the substantia nigra and striatum. Cerebrolysin coadministered with rotenone decreased lipid peroxidation, increased GSH, and inhibited the elevation of nitric oxide induced by rotenone. Cerebrolysin also decreased the rotenone-induced decline in the PON1 and AChE activities and the rotenone-mediated changes in the striatal Bcl-2 and MCP-1 levels. The drug reduced iNOs, TNF-α, and caspase 3 expressions and increased the tyrosine hydroxylase immunoreactivity in the striatum. Cerebrolysin markedly prevented the development of neuronal damage in the cortex and striatum. These data suggest that cerebrolysin may have potential therapeutic effect in Parkinson’s disease.

Key wordsbrain oxidative stress      neuroinflammation      apoptosis      nigrostriatal damage     
Published: 26 December 2014
Corresponding Authors: Omar ME Abdel-Salam, Department of Toxicology and Narcotics, National Research Centre, 33 Tahrir Street, Dokki, Cairo, Egypt, Tel +20 233 371 362, Fax +20 233 370 931, Email   
Cite this article:

Omar ME Abdel-Salam, Nadia A Mohammed, Eman R Youness, Yasser A Khadrawy, Enayat A Omara, Amany A Sleem. Cerebrolysin protects against rotenone-induced oxidative stress and neurodegeneration. Journal of Neurorestoratology, 2014, 2: 47-64.

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