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The involvement of cholesterol in sepsis and tolerance to lipopolysaccharide highlighted by the transcriptome analysis of zebrafish (Danio rerio)

Citation
Dios S, Balseiro P, Costa MM, Romero A, Boltana S, Roher N, MacKenzie S, Figueras A & Novoa B (2014) The involvement of cholesterol in sepsis and tolerance to lipopolysaccharide highlighted by the transcriptome analysis of zebrafish (Danio rerio), Zebrafish, 11 (5), pp. 421-433.

Abstract
Septic shock is the most common cause of death in intensive care units due to an aggressive inflammatory response that leads to multiple organ failure. However, a lipopolysaccharide (LPS) tolerance phenomenon (a nonreaction to LPS), is also often described. Neither the inflammatory response nor the tolerance is completely understood. In this work, both of these responses were analyzed using microarrays in zebrafish. Fish that were 4 or 6 days postfertilization (dpf) and received a lethal dose (LD) of LPS exhibited 100% mortality in a few days. Their transcriptome profile, even at 4 dpf, resembled the profile in humans with severe sepsis. Moreover, we selected 4-dpf fish to set up a tolerance protocol: fish treated with a nonlethal concentration of Escherichia coli LPS exhibited complete protection against the LD of LPS. Most of the main inflammatory molecules described in mammals were represented in the zebrafish microarray experiments. Additionally and focusing on this tolerance response, the use of cyclodextrins may mobilize cholesterol reservoirs to decrease mortality after a LD dose of LPS. Therefore, it is possible that the use of the whole animal could provide some clues to enhance the understanding of the inflammatory/tolerance response and to guide drug discovery.

StatusPublished
AuthorsDios Sonia, Balseiro Pablo, Costa Maria M, Romero Alejandro, Boltana Sebastian, Roher Nerea, MacKenzie Simon, Figueras Antonio, Novoa Beatriz
Publication date09/2014
PublisherMary Ann Liebert, Inc.
ISSN 1545-8547
LanguageEnglish

Journal
Zebrafish: Volume 11, Issue 5 (2014)

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