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RETRACTED ARTICLE: Anti-Inflammatory Effects of Chronic Aspirin on Brain Arachidonic Acid Metabolites

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This article was retracted on 25 April 2015

Abstract

Pro-inflammatory and anti-inflammatory mediators derived from arachidonic acid (AA) modulate peripheral inflammation and its resolution. Aspirin (ASA) is a unique non-steroidal anti-inflammatory drug, which switches AA metabolism from prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) to lipoxin A4 (LXA4) and 15-epi-LXA4. However, it is unknown whether chronic therapeutic doses of ASA are anti-inflammatory in the brain. We hypothesized that ASA would dampen increases in brain concentrations of AA metabolites in a rat model of neuroinflammation, produced by a 6-day intracerebroventricular infusion of bacterial lipopolysaccharide (LPS). In rats infused with LPS (0.5 ng/h) and given ASA-free water to drink, concentrations in high-energy microwaved brain of PGE2, TXB2 and leukotriene B4 (LTB4) were elevated. In rats infused with artificial cerebrospinal fluid, 6 weeks of treatment with a low (10 mg/kg/day) or high (100 mg/kg/day) ASA dose in drinking water decreased brain PGE2, but increased LTB4, LXA4 and 15-epi-LXA4 concentrations. Both doses attenuated the LPS effects on PGE2, and TXB2. The increments in LXA4 and 15-epi-LXA4 caused by high-dose ASA were significantly greater in LPS-infused rats. The ability of ASA to increase anti-inflammatory LXA4 and 15-epi-LXA4 and reduce pro-inflammatory PGE2 and TXB2 suggests considering aspirin further for treating clinical neuroinflammation.

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Abbreviations

AA:

Arachidonic acid

aCSF:

Artificial cerebrospinal fluid

COX:

Cyclooxygenase

ELISA:

Enzyme-linked immunosorbent assay

HETE:

Hydroxyeicosatetraenoic acid

icv:

Intracerebroventricular

IL:

Interleukin

LPS:

Lipopolysaccharide

LT:

Leukotriene

LXA4 :

Lipoxin A4

15-epi-LXA4 :

15-epimeric-lipoxin A4

LOX:

Lipoxygenase

PLA2 :

Phospholipase A2

cPLA2 :

Cytosolic PLA2

sPLA2 :

Secretory PLA2

PGE2 :

Prostaglandin E2

TXB2 :

Thromboxane B2

NSAID:

Non-steroidal anti-inflammatory drug

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Acknowledgments

This work was supported entirely by the Intramural Research Program of the National Institute on Aging, NIH. None of the authors has a financial or other conflict of interest related to this work.

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Authors and Affiliations

  1. Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bldg. 9, Room 1S126, 9000 Rockville Pike, Bethesda, MD, 20892, USA

    Mireille Basselin, Epolia Ramadan, Mei Chen & Stanley I. Rapoport

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  1. Mireille Basselin
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  2. Epolia Ramadan
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  3. Mei Chen
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  4. Stanley I. Rapoport
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Correspondence to Epolia Ramadan.

Additional information

An erratum to this article is available at http://dx.doi.org/10.1007/s11064-015-1583-4.

This article has been retracted on request of the Editor-in-Chief. The National Institutes of Health (NIH) has found that Dr. Mireille Basselin engaged in research misconduct by fabricating and/or falsifying data in "Basselin M, Ramadan E, Chen M, Rapoport SI, Anti-inflammatory effects of chronic aspirin on brain arachidonic acid metabolites. Neurochemical Research 36 (1) 139-145, 2011." Figure 2 A-E was falsified. Please note, none of the other authors are implicated in any way. Each of the co-authors of the manuscript has agreed to this retraction.

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Basselin, M., Ramadan, E., Chen, M. et al. RETRACTED ARTICLE: Anti-Inflammatory Effects of Chronic Aspirin on Brain Arachidonic Acid Metabolites. Neurochem Res 36, 139–145 (2011). https://doi.org/10.1007/s11064-010-0282-4

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