Nitric oxide synthesis inhibition attenuates iron-induced neurotoxicity: a stereological study.
Iron overload and enhanced hydroxyl radical formation have been implicated as the causative factors of some neurodegenerative disorders. Therefore, iron is commonly used as a metal to induce neuronal hyperactivity and oxidative stress. A body of evidence indicates a relationship between iron-induced neuronal death and nitric oxide (NO). Data are, however, controversial because it is not clear whether NO has neuroprotective or neurotoxic effects on neurotoxicity. To determine the contribution of NO to iron-induced hippocampal cell loss, l-arginine, the NO synthesis precursor, and a nonselective nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME) were used. Animals were divided into four groups as follows: control, iron, iron+l-NAME and iron+l-arginine. Neurotoxicity was produced by microinjection of iron chloride (200 mM, 2.5 microl) into the left cerebral ventricle in iron-treated groups while control group rats received same amount of saline. After the intracerebroventricular injection, all animals were kept alive for 10 days. During this period, animals in iron+l-NAME and iron+l-arginine groups received intraperitoneal (i.p.) l-NAME (30 mg/kg) and l-arginine (1000 mg/kg) injections once a day, respectively. Rats belonging to control group also received the same amount of saline intraperitoneally. 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 stereological techniques. It was found that l-NAME decreased iron-induced cell loss from 44.7 to 13.7%, while l-arginine increased cell loss from 44.7 to 57.5%. Results of the present study suggest that inhibition of NO synthesis may attenuate the neurotoxic effects of iron.
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; D001120:Arginine / Q000494:pharmacology; D004195:Disease Models, Animal; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000473:pathology; D007501:Iron / Q000378:metabolism / Q000633:toxicity*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D009474:Neurons / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013238:Stereotaxic Techniques
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D001120:Arginine; D007501:Iron; D019331:NG-Nitroarginine Methyl Ester