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P-hydroxyphenylpyruvate, an intermediate of the Phe/Tyr catabolism, improves mitochondrial oxidative metabolism under stressing conditions and prolongs survival in rats subjected to profound hemorrhagic shock

Cotoia, A and Scrima, R and Gefter, JV and Piccoli, C and Cinnella, G and Dambrosio, M and Fink, MP and Capitanio, N (2014) P-hydroxyphenylpyruvate, an intermediate of the Phe/Tyr catabolism, improves mitochondrial oxidative metabolism under stressing conditions and prolongs survival in rats subjected to profound hemorrhagic shock. PLoS ONE, 9 (3).

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Abstract

The aim of this study was to test the effect of a small volume administration of p-hydroxyphenylpyruvate (pHPP) in a rat model of profound hemorrhagic shock and to assess a possible metabolic mechanism of action of the compound. The results obtained show that hemorrhaged rats treated with 2-4% of the estimated blood volume of pHPP survived significantly longer (p<0.001) than rats treated with vehicle. In vitro analysis on cultured EA.hy 926 cells demonstrated that pHPP improved cell growth rate and promoted cell survival under stressing conditions. Moreover, pHPP stimulated mitochondria-related respiration under ATP-synthesizing conditions and exhibited antioxidant activity toward mitochondria-generated reactive oxygen species. The compound effects reported in the in vitro and in vivo analyses were obtained in the same millimolar concentration range. These data disclose pHPP as an efficient energetic substrates-supplier to the mitochondrial respiratory chain as well as an antioxidant supporting the view that the compound warrants further evaluation as a therapeutic agent. © 2014 Cotoia et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Cotoia, A
Scrima, R
Gefter, JV
Piccoli, C
Cinnella, G
Dambrosio, M
Fink, MP
Capitanio, N
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorScorrano, LucaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 5 March 2014
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 9
Number: 3
DOI or Unique Handle: 10.1371/journal.pone.0090917
Schools and Programs: School of Medicine > Critical Care Medicine
Refereed: Yes
Date Deposited: 23 Jun 2014 21:30
Last Modified: 23 Jan 2019 22:55
URI: http://d-scholarship.pitt.edu/id/eprint/21935

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