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.

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.

• Authors: Antonella Cotoia, Rosella Scrima, Julia V Gefter, Claudia Piccoli, Gilda Cinnella, Michele Dambrosio, Mitchell P Fink, Nazzareno Capitanio
• Journal: PloS one (PLoS One) Vol. 9 Issue 3 Pg. e90917 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 24599095 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Phenylpyruvic Acids
• Reactive Oxygen Species
• Superoxides
• 4-hydroxyphenylpyruvic acid
• Tyrosine
• Phenylalanine

Topics

• Animals
• Cell Line
• Cell Proliferation (drug effects)
• Cell Respiration (drug effects)
• Cell Survival (drug effects)
• Hemodynamics (drug effects)
• Humans
• Metabolic Networks and Pathways (drug effects)
• Mitochondria (drug effects, metabolism)
• Oxidation-Reduction
• Phenylalanine (metabolism)
• Phenylpyruvic Acids (pharmacology, therapeutic use)
• Rats
• Reactive Oxygen Species (metabolism)
• Shock, Hemorrhagic (chemically induced, drug therapy, metabolism, physiopathology)
• Stress, Physiological (drug effects)
• Subcellular Fractions (drug effects, metabolism)
• Superoxides (metabolism)
• Survival Analysis
• Tyrosine (metabolism)