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Biologia




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Volume 70, Issue 5

Issues

Effect of novel quercetin pivaloyl ester on functions of adult rat microglia

Marcela Kuniaková
  • Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University, Bratislava, Slovakia
  • Other articles by this author:
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/ Nataša Mrvová
  • Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, Slovakia;
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/ Vladimír Knezl
  • Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, Slovakia;
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/ Lucia Račková
  • Corresponding author
  • Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, Slovakia
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Published Online: 2015-06-23 | DOI: https://doi.org/10.1515/biolog-2015-0082

Abstract

The pathogenic mechanisms involved in the development of ageing-related neurodegenerative diseases can involve alterations of microglia, the brain counterpart of macrophages. These include microglial over-activation, replicative senescence, accumulation of autofluorescent lipofuscin and mitochondrial dysfunction. Substantial evidence suggests that dietary flavonoids are capable to modulate and probably revert the hyperactive and senescence phenotype of these cells. The present study assessed the effect of a novel semisynthetic flavonoid 3’-O-(3-chloropivaloyl)quercetin (CPQ) on the functions of adult rat microglia, isolated secondarily to the establishment of mixed glial cultures and compared it with the effect of the unmodified molecule, quercetin. CPQ suppressed NO release by lipopolysaccharide-stimulated cells more effectively than did quercetin. Unlike quercetin, CPQ inhibited the injury of cell viability due to oxidative challenge and suppressed senescence-associated β-galactosidase staining of microglia isolated from long-term mixed glial cultures. Both flavonoids tested protected the functions of microglia in response to inflammatory stimuli. Furthermore, both compounds protected the isolated microglia from adverse effects of HEPES-buffered media. This was followed by an increase of cell yields, improvement of lysosomal function, suppression of nuclear protein oxidation and inhibition of lipofuscin accumulation (at a slightly more profound effect of CPQ). In conclusion, our data support the experimental evidence suggesting beneficial effects of flavonoids in modulation of neuropathology- and ageing-related alterations of microglia. In this regard, the novel pivaloyl ester of quercetin might represent a new drug with improved potential against neurodegenerative diseases.

Keywords: microglia; ageing; activation; senescence; flavonoids; neurodegeneration

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About the article

Received: 2015-03-01

Accepted: 2015-05-02

Published Online: 2015-06-23

Published in Print: 2015-05-01


Citation Information: Biologia, Volume 70, Issue 5, Pages 690–702, ISSN (Online) 1336-9563, ISSN (Print) 0006-3088, DOI: https://doi.org/10.1515/biolog-2015-0082.

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