Central Nervous System Agents in Medicinal Chemistry

(Formerly Current Medicinal Chemistry - Central Nervous System Agents)

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Prophylaxis with Bacopa monnieri Attenuates Acrylamide Induced Neurotoxicity and Oxidative Damage via Elevated Antioxidant Function

Author(s): George Kunnel Shinomol, Narayanareddy Raghunath, Muchukunte Mukunda Srinivas Bharath, Muralidhara.

Abstract:

Acrylamide (ACR) is a water-soluble, vinyl monomer that has multiple chemical and industrial applications. Exposure to ACR causes neuropathy and associated neurological defects including gait abnormalities and skeletal muscle weakness, due to impaired neurotransmitter release and eventual neurodegeneration. Using in vivo and in vitro models, we examined whether oxidative events are involved in ACR-mediated neurotoxicity and whether these could be prevented by natural plant extracts. Administration (i.p.) of ACR in mice (40 mg/kg bw/ d for 5d) induced significant oxidative damage in the brain cortex and liver as evidenced by elevated lipid peroxidation, reactive oxygen species and protein carbonyls. This was associated with lowered antioxidant activities including antioxidant enzymes (catalase, glutathione-s-transferase) and reduced glutathione (GSH) compared to untreated controls. Similarly, exposure of N27 neuronal cells in culture to ACR (1-5 mM) caused dose-dependent neuronal death and lowered GSH. Interestingly, dietary supplementation with the leaf powder of Bacopa monnieri (BM) (which possesses neuroprotective properties and nootropic activity) in mice for 30 days offered significant protection against ACR toxicity and oxidative damage in vivo. Similarly, pretreatment with BM protected the N27 cells against ACR-induced cell death and associated oxidative damage. Co-treatment and pre-treatment of Drosophila melanogaster with BM extract protected against ACR-induced locomotor dysfunction and GSH depletion. We infer that BM displays prophylactic effects against ACR induced oxidative damage and neurotoxicity with potential therapeutic application in human pathology associated with neuropathy.

Keywords: Acrylamide, Bacopa monnieri, glutathione, neuropathy, neurotoxicity, oxidative stress

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Article Details

VOLUME: 13
ISSUE: 1
Year: 2013
Page: [3 - 12]
Pages: 10
DOI: 10.2174/1871524911313010003