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Fisetin enhances behavioral performances and attenuates reactive gliosis and inflammation during aluminum chloride-induced neurotoxicity.

Abstract：

:Aluminum (Al) is an environmental neurotoxin that affects cerebral functions and causes health complications. However, the role of Al in arbitrating glia homeostasis and pathophysiology remains obscure. Astrocyte, microglia activation (reactive gliosis), and associated inflammatory events play a decisive role in neurodegeneration and may represent a target for treating neurodegenerative disorders. In this study, we have analyzed the role of aluminum chloride (AlCl3) in causing reactive gliosis in the brain of mice and the ability of fisetin, a flavonoid to attenuate reactive gliosis and neuronal inflammation. Reports suggest that fisetin exerts antioxidant and anti-inflammatory actions. Fisetin at a dose of 15 mg/kg body weight was orally administered, daily (pre-treated for 4 weeks before AlCl3 induction and co-treated until experimental period of 8 weeks) to mice induced with AlCl3 (200 mg/kg b.wt./day/8 weeks, orally). Administration of AlCl3 developed behavioral deficits, triggered lipid peroxidation (LPO), compromised acetylcholine esterase (AChE) activity, and reduced the levels of superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), and reduced glutathione (GSH), and caused histologic aberrations. These effects were accompanied by increased expressions of Glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1. Pro-inflammatory cytokines, such as tumor necrosis factor alpha, interleukin-1β, inducible nitric oxide synthase, were increased upon AlCl3 administration. AlCl3-induced alterations in the activities of SOD, CAT, GST, AChE and levels of GSH, LPO, activity of AChE, behavioral deficits, histologic aberrations, reactive gliosis, and inflammatory niche were attenuated on treatment with fisetin. Collectively, our results indicate that fisetin exerts neuroprotection against AlCl3-induced brain pathology.

journal_name

Neuromolecular Med

journal_title

Neuromolecular medicine

authors

Prakash D,Gopinath K,Sudhandiran G

doi

10.1007/s12017-012-8210-1

subject

Has Abstract

pub_date

2013-03-01 00:00:00

pages

192-208

issue

eissn

1535-1084

issn

1559-1174

journal_volume

pub_type

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Fisetin enhances behavioral performances and attenuates reactive gliosis and inflammation during aluminum chloride-induced neurotoxicity.