Aminoguanidine inhibits reactive oxygen species formation, lipid peroxidation, and oxidant-induced apoptosis
Aminoguanidine inhibits reactive oxygen species formation, lipid peroxidation, and oxidant-induced apoptosis. I Giardino , A K Fard , D L Hatchell and M Brownlee Department of Medicine and the Diabetes Research Center, Albert Einstein College of Medicine, Bronx, New York 10461, USA. Abstract Aminogu...
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Published in | Diabetes (New York, N.Y.) Vol. 47; no. 7; pp. 1114 - 1120 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Alexandria, VA
American Diabetes Association
01.07.1998
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Subjects | |
Online Access | Get full text |
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Summary: | Aminoguanidine inhibits reactive oxygen species formation, lipid peroxidation, and oxidant-induced apoptosis.
I Giardino ,
A K Fard ,
D L Hatchell and
M Brownlee
Department of Medicine and the Diabetes Research Center, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Abstract
Aminoguanidine (AG) treatment, like nerve growth factor (NGF) treatment, prevents diabetes-induced apoptosis of retinal Müller
cells in the rat eye, but the mechanism involved is unknown. In this study, the effects of preincubation with AG on oxidant-induced
apoptosis, oxidant-induced intracellular reactive oxygen species (ROS) production, and lipid peroxidation were determined
in rat retinal Müller cells and compared with the effects of NGF, a protein that protects neuronal cells from oxidative stress.
The effect of AG on rabbit vitreous lipid peroxide levels was also determined. After exposure to increasing concentrations
of H2O2, there was a corresponding increase in the percentage of apoptotic Müller cells. Preincubation with AG for 48 h completely
inhibited oxidant-induced apoptosis in response to 10 micromol/l H2O2 (+AG 0 vs. 10 micromol/l, NS), and reduced the percentage
of apoptotic cells in response to 50 micromol/l H2O2 by 50% (+AG vs. -AG, P < 0.01). Longer preincubation did not increase
the antiapoptotic effect of AG. The effect of AG was dose-dependent. Similar results were obtained after preincubation with
NGF. Both AG and NGF preincubation prevented the twofold increase in oxidant-induced lipid peroxides. The fivefold increase
in oxidant-induced ROS production was decreased 100% by NGF, but only 61% by AG preincubation. The twofold increase in vitreous
lipid peroxide level in diabetic rabbits was completely prevented by AG treatment. AG reduced H2O2-induced benzoate hydroxylation
in a dose-dependent manner. Intracellular glutathione content was unchanged. These data demonstrate that AG can act as an
antioxidant in vivo, quenching hydroxyl radicals and lipid peroxidation in cells and tissues and preventing oxidant-induced
apoptosis. |
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ISSN: | 0012-1797 1939-327X |
DOI: | 10.2337/diabetes.47.7.1114 |