title: Aminoguanidine inhibits reactive oxygen species formation, lipid peroxidation, and oxidant-induced apoptosis.
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.
authors.affiliation: Department of Medicine and the Diabetes Research Center, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: I
authors.initials: I
authors.lastname: Giardino
authors.forename: A K
authors.initials: AK
authors.lastname: Fard
authors.forename: D L
authors.initials: DL
authors.lastname: Hatchell
authors.forename: M
authors.initials: M
authors.lastname: Brownlee
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D009414:Nerve Growth Factors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D016877:Oxidants / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012160:Retina / Q000378:metabolism*; D014822:Vitreous Body / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D006146:Guanidines; D009414:Nerve Growth Factors; D016877:Oxidants; D017382:Reactive Oxygen Species; D017665:Hydroxyl Radical; D006861:Hydrogen Peroxide; D019001:Nitric Oxide Synthase; C004479:pimagedine