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Fisetin Enhances Behavioral Performances and Attenuates Reactive Gliosis and Inflammation During Aluminum Chloride-Induced Neurotoxicity.
MedLine Citation:
PMID:  23315010     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 (AlCl(3)) 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 AlCl(3) induction and co-treated until experimental period of 8 weeks) to mice induced with AlCl(3) (200 mg/kg b.wt./day/8 weeks, orally). Administration of AlCl(3) 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 AlCl(3) administration. AlCl(3)-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 AlCl(3)-induced brain pathology.
Authors:
Dharmalingam Prakash; Kulasekaran Gopinath; Ganapasam Sudhandiran
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-13
Journal Detail:
Title:  Neuromolecular medicine     Volume:  -     ISSN:  1559-1174     ISO Abbreviation:  Neuromolecular Med.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101135365     Medline TA:  Neuromolecular Med     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Biochemistry, Cell Biology Laboratory, University of Madras, Guindy Campus, Chennai, 600025, Tamilnadu, India.
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