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Protective effect of vinpocetine against neurotoxicity of manganese in adult male rats

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Abstract

Manganese (Mn) is required for many essential biological processes as well as in the development and functioning of the brain. Extensive accumulation of Mn in the brain may cause central nervous system dysfunction known as manganism, a motor disorder associated with cognitive and neuropsychiatric deficits similar to parkinsonism. Vinpocetine, a synthetic derivative of the alkaloid vincamine, is used to improve the cognitive function in cerebrovascular diseases. It possesses antioxidant and antiinflammatory properties. The present work was designed to explore the potential neuroprotective mechanisms exerted by vinpocetine in the Mn-induced neurotoxicity in rats. Rats were allocated into four groups. First group was given saline. The other three groups were given MnCl2; two of them were treated with either l-dopa, the gold standard antiparkinsonian drug, or vinpocetine. Rats receiving MnCl2 exhibited lengthened catalepsy duration in the grid and bar tests, motor impairment in the open-field test and short-term memory deficit in the Y-maze test. Additionally, histological examination revealed structural alterations and degeneration in different brain regions. Besides, striatal monoamines and mitochondrial complex I contents were declined, apoptotic biomarker caspase-3 expression and acetylcholinesterase activity were elevated. Moreover, oxidative stress and inflammation were detected in the striata. l-dopa or vinpocetine exerted protective effects against MnCl2-induced neurotoxicity. It could be hypothesized that modulation of monoamines, upregulation of mitochondrial complex I, antioxidant, antiinflammatory, and antiapoptotic activities are significant mechanisms underlying the neuroprotective effect of vinpocetine in the Mn-induced neurotoxicity model in rats.

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Abbreviations

AChE:

Acetylcholinesterase

DA:

Dopamine

H&E:

Hematoxylin and eosin

IL-1β:

Interleukin-1 beta

MDA:

Malondialdehyde

Mn:

Manganese

NA:

Noradrenaline

PDE:

Phosphodiesterase

ROS:

Reactive oxygen species

5-HT:

Serotonin

SOD:

Superoxide dismutase

TAC:

Total antioxidant capacity

TNF-α:

Tumor necrosis factor-alpha

α-Syn:

α-synuclein

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Authors and Affiliations

  1. Cairo, Egypt

    Rania I. Nadeem

  2. Department of Pharmacology and Toxicology, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt

    Hebatalla I. Ahmed

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

    Bahia M. El-Sayeh

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  1. Rania I. Nadeem
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Correspondence to Hebatalla I. Ahmed.

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The study complies with the Guide for the Care and Use of Laboratory Animals published by the National Institutes of Health (NIH Publications No. 8023, revised 1978) and is approved by the Ethics Committee of Faculty of Pharmacy, Cairo University.

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Nadeem, R.I., Ahmed, H.I. & El-Sayeh, B.M. Protective effect of vinpocetine against neurotoxicity of manganese in adult male rats. Naunyn-Schmiedeberg's Arch Pharmacol 391, 729–742 (2018). https://doi.org/10.1007/s00210-018-1498-0

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  • DOI: https://doi.org/10.1007/s00210-018-1498-0

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