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Hydralazine rescues PC12 cells from acrolein‐mediated death
Author(s) -
LiuSnyder Peishan,
Borgens Richard Ben,
Shi Riyi
Publication year - 2006
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.20862
Subject(s) - acrolein , lipid peroxidation , pharmacology , population , toxicity , chemistry , programmed cell death , free radical scavenger , oxidative stress , medicine , biochemistry , apoptosis , environmental health , catalysis
Acrolein, a major lipid peroxidation product, has been associated with both CNS trauma and neurodegenerative diseases. Because of its long half‐life, acrolein is a potent endogenous toxin capable of killing healthy cells during the secondary injury process. Traditionally, attempts to intervene in the process of progressive cell death after the primary injury have included scavenging reactive oxygen species (so‐called free radicals). The animal data supporting such an approach have generally been positive, but all human clinical trials attempting a similar outcome in human CNS injury have failed. New drugs that might reduce toxicity by scavenging the products of lipid peroxidation present a promising, and little investigated, therapeutic approach. Hydralazine, a well‐known treatment for hypertension, has been reported to react with acrolein, forming hydrazone in cell‐free systems. In the companion paper, we have established an acrolein‐mediated cell injury model using PC12 cells in vitro. Here we test the hypothesis that the formation of hydrazone adducts with acrolein is able to reduce acrolein toxicity and spare a significant percentage of the population of PC12 cells from death. Concentrations of approximately 1 mM of this aldehyde scavenger can rescue over 80% of the population of PC12 cells. This study provides a basis for a new pharmacological treatment to reduce the effects of secondary injury in the damaged and/or diseased nervous system. In particular, we describe the need for new drugs that possess aldehyde scavenging properties but do not interfere with the regulation of blood pressure. © 2006 Wiley‐Liss, Inc.