TY - JOUR
T1 - Antioxidant activity of U-83836E, a second generation lazaroid, during myocardial Ischemia/Reperfusion injury
AU - Campo, Giuseppe M.
AU - Squadrito, Francesco
AU - Campo, Salvatore
AU - Altavilla, Domenica
AU - Avenoso, Angela
AU - Ferlito, Marcella
AU - Squadrito, Giovanni
AU - Caputi, Achille P.
N1 - Funding Information:
This work was partially supported by CNR (National Research Council), Italy (grant n"9502181CT04) and MURST 40%. We gratefully acknowledge the Upjohn SPA, Caponago (MI), Italy for the generous supply of U-83836E.
PY - 1997
Y1 - 1997
N2 - The 21-aminosteroid compounds are potent lipid per oxidation inhibitors belonging to a new class of antioxidants given the collective name of 'lazaroids'. They protect cells from oxidative damage induced by oxygen-based free radicals in a variety of in vitro and in vivo test systems. U-83836E is one of the second-generation lazaroids that are based on a non steroidal structure characterized by a ring portion of α-tocopherol bonded with various amine groups. We investigated the ability of U-83836E to reduce myocardial damage in rats undergoing left coronary artery occlusion for 60 min followed by 6 hours of reperfusion. This ischemia/reperfusion model produced wide heart necrosis, membrane lipid peroxidation, ventricular arrhythmias, tissue neutrophil infiltration and a marked decrease in endogenous antioxidants. Intravenous administration of U-83836E, (7.5, 15 and 30 mg/kg) at onset of reperfusion, reduced myocardial necrosis, expressed as a percentage of either the area at risk or the total left ventricle (p < 0.001), improved haemodynamic conditions by decreasing ventricular arrhythmias (p < 0.005), limited membrane lipid peroxidation (evaluated by assessing conjugated dienes, p < 0.001; and 4-hydroxy-nonenal, p < 0.001) restored the endogenous antioxidants vitamin E (p < 0.001), and superoxide dismutase (pt < 0.001). Furthermore, the lazaroid inhibited the derimental hydroxyl radical formation (p < 0.001), evaluated indirectly by a trapping agent and reduced heart neutrophil infiltration, measured by testing cardiac tissue elastase (p < 0.001) that is released from the stimulated granulocytes at the site of injury. These data suggest that this compound could be a new useful tool to study the mechanisms of oxidative damage during myocardial infarction.
AB - The 21-aminosteroid compounds are potent lipid per oxidation inhibitors belonging to a new class of antioxidants given the collective name of 'lazaroids'. They protect cells from oxidative damage induced by oxygen-based free radicals in a variety of in vitro and in vivo test systems. U-83836E is one of the second-generation lazaroids that are based on a non steroidal structure characterized by a ring portion of α-tocopherol bonded with various amine groups. We investigated the ability of U-83836E to reduce myocardial damage in rats undergoing left coronary artery occlusion for 60 min followed by 6 hours of reperfusion. This ischemia/reperfusion model produced wide heart necrosis, membrane lipid peroxidation, ventricular arrhythmias, tissue neutrophil infiltration and a marked decrease in endogenous antioxidants. Intravenous administration of U-83836E, (7.5, 15 and 30 mg/kg) at onset of reperfusion, reduced myocardial necrosis, expressed as a percentage of either the area at risk or the total left ventricle (p < 0.001), improved haemodynamic conditions by decreasing ventricular arrhythmias (p < 0.005), limited membrane lipid peroxidation (evaluated by assessing conjugated dienes, p < 0.001; and 4-hydroxy-nonenal, p < 0.001) restored the endogenous antioxidants vitamin E (p < 0.001), and superoxide dismutase (pt < 0.001). Furthermore, the lazaroid inhibited the derimental hydroxyl radical formation (p < 0.001), evaluated indirectly by a trapping agent and reduced heart neutrophil infiltration, measured by testing cardiac tissue elastase (p < 0.001) that is released from the stimulated granulocytes at the site of injury. These data suggest that this compound could be a new useful tool to study the mechanisms of oxidative damage during myocardial infarction.
KW - Antioxidants
KW - Free radicals
KW - Lazaroids
KW - Lipid peroxidation,
KW - Myocardial injury
KW - Vitamin E
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U2 - 10.3109/10715769709097861
DO - 10.3109/10715769709097861
M3 - Article
C2 - 9455693
AN - SCOPUS:0031461386
SN - 1071-5762
VL - 27
SP - 577
EP - 590
JO - Free Radical Research
JF - Free Radical Research
IS - 6
ER -