TY - JOUR
T1 - The antihypertensive hydralazine is an efficient scavenger of acrolein
AU - Burcham, P. C.
AU - Kerr, P. G.
AU - Fontaine, F
N1 - Cited By (since 1996): 16 Export Date: 2 November 2011 Source: Scopus CODEN: RDRPE PubMed ID: 10905545 Language of Original Document: English Correspondence Address: Burcham, P.C.; Dept. Clin./Experimental Pharmacol., University of Adelaide, Adelaide, SA 5005, Australia; email: [email protected]
PY - 2000
Y1 - 2000
N2 - Recent work indicates the highly toxic α,β-unsaturated aldehyde acrolein is formed during the peroxidation of polyunsaturated lipids, raising the possibility that it functions as a 'toxicological second messenger' during oxidative cell injury. Acrolein reacts rapidly with proteins, forming adducts that retain carbonyl groups. Damage by this route may thus contribute to the burden of carbonylated proteins in tissues. This work evaluated several amine compounds with known aldehyde-scavenging properties for their ability to attenuate protein carbonylation by acrolein. The compounds tested were: (i) the glycoxidation inhibitors, aminoguanidine and carnosine; (ii) the antihypertensive, hydralazine; and (iii) the classic carbonyl reagent, methoxyamine. Each compound attenuated carbonylation of a model protein, bovine serum albumin, during reactions with acrolein at neutral pH and 37°C. However, the most efficient agent was hydralazine, which strongly suppressed carbonylation under these conditions. Study of the rate of reaction between acrolein and the various amines in a protein-free buffered system buttressed these findings, since hydralazine reacted with acrolein at rates 2-3 times faster than its reaction with the other scavengers. Hydralazine also protected isolated mouse hepatocytes against cell killing by allyl alcohol, which undergoes in situ alcohol dehydrogenase-catalysed conversion to acrolein.
AB - Recent work indicates the highly toxic α,β-unsaturated aldehyde acrolein is formed during the peroxidation of polyunsaturated lipids, raising the possibility that it functions as a 'toxicological second messenger' during oxidative cell injury. Acrolein reacts rapidly with proteins, forming adducts that retain carbonyl groups. Damage by this route may thus contribute to the burden of carbonylated proteins in tissues. This work evaluated several amine compounds with known aldehyde-scavenging properties for their ability to attenuate protein carbonylation by acrolein. The compounds tested were: (i) the glycoxidation inhibitors, aminoguanidine and carnosine; (ii) the antihypertensive, hydralazine; and (iii) the classic carbonyl reagent, methoxyamine. Each compound attenuated carbonylation of a model protein, bovine serum albumin, during reactions with acrolein at neutral pH and 37°C. However, the most efficient agent was hydralazine, which strongly suppressed carbonylation under these conditions. Study of the rate of reaction between acrolein and the various amines in a protein-free buffered system buttressed these findings, since hydralazine reacted with acrolein at rates 2-3 times faster than its reaction with the other scavengers. Hydralazine also protected isolated mouse hepatocytes against cell killing by allyl alcohol, which undergoes in situ alcohol dehydrogenase-catalysed conversion to acrolein.
KW - acrolein alcohol dehydrogenase aldehyde allyl alcohol aminoguanidine antihypertensive agent bovine serum albumin carbonyl derivative carnosine hydralazine lactate dehydrogenase methoxyamine polyunsaturated fatty acid scavenger animal cell article catalysi
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U2 - 10.1179/rer.2000.5.1.47
DO - 10.1179/rer.2000.5.1.47
M3 - Article
SN - 1351-0002
VL - 5
SP - 47
EP - 49
JO - Redox Report
JF - Redox Report
IS - 1
ER -