Neuroprotective effect of aminoguanidine on iron-induced neurotoxicity.
Iron is a commonly used metal to induce neuronal hyperactivity and oxidative stress. Iron levels rise in the brain in some neurodegenerative disorders such as Parkinson's and Alzheimer's diseases. A body of evidence indicates a link between neuronal death and nitric oxide. The present study was performed to investigate whether nitric oxide produced by inducible nitric oxide synthase is involved in iron-induced neuron death. For this purpose rats were divided into four groups: control, iron, aminoguanidine and iron+aminoguanidine. Animals in iron and iron+aminoguanidine groups received intracerebroventricular FeCl3 injection (200 mM, 2.5 microl). Rats belonging to control and aminoguanidine groups received the same amount of saline into the cerebral ventricles. All animals were kept alive for 10 days following the operation and animals in aminoguanidine and iron+aminoguanidine groups received intraperitoneal aminoguanidine injections once a day (100mg/kg day) during this period. After 10 days, rats were perfused intracardially under deep urethane anesthesia. Removed brains were processed using the standard histological techniques. The total numbers of neurons in hippocampus of all rats were estimated with the unbiased stereological techniques. It was found that aminoguanidine decreased mean neuron loss from 43.4% to 20.3%. Results of the present study suggest that aminoguanidine may attenuate the neurotoxic effects of iron by inhibiting inducible nitric oxide synthase.
Bostanci
M Omer
MO
Department of Physiology, Faculty of Medicine, Ondokuz Mayis University, 55139 Samsun, Turkey. mehmetob@omu.edu.tr
Bağirici
Faruk
F
D000818:Animals; D002712:Chlorides; D004791:Enzyme Inhibitors / Q000378:metabolism*; D005290:Ferric Compounds / Q000008:administration & dosage / Q000633:toxicity*; D006146:Guanidines / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology; D008297:Male; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism*; D020258:Neurotoxicity Syndromes; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D009676:Noxae / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
D002712:Chlorides; D004791:Enzyme Inhibitors; D005290:Ferric Compounds; D006146:Guanidines; D018696:Neuroprotective Agents; D009676:Noxae; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C004479:pimagedine; C024555:ferric chloride