Neuroprotective Effect of Intermittent Hypoxia on Iron-Induced Oxidative Injury in Rat Brain

• Published in: Experimental neurology 2002-08, Vol.176 (2), p.328-335
• Main Authors: Lin, Anya M.Y., Chen, C.F., Ho, L.T.
• Format: Article
• Language: English
• Subjects: Animals; antioxidative enzyme activity; Atmosphere Exposure Chambers; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Brain - pathology; Buthionine Sulfoximine - administration & dosage; Catalase - metabolism; Disease Models, Animal; Drug Administration Routes; Female; Glutathione - metabolism; Glutathione Disulfide - metabolism; Glutathione Peroxidase - metabolism; GSH; GSH/GSSG ratio; Hypoxia - physiopathology; Injuries of the nervous system and the skull. Diseases due to physical agents; intermittent hypoxia; iron; Iron - administration & dosage; L-BSO; Medical sciences; oxidative injury; Parkinson Disease - pathology; Parkinson Disease - physiopathology; Parkinson Disease, Secondary - chemically induced; Rats; Rats, Wistar; Substantia Nigra - drug effects; Substantia Nigra - metabolism; Substantia Nigra - pathology; Superoxide Dismutase - metabolism; Traumas. Diseases due to physical agents
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1006/exnr.2002.7938

The neuroprotective effect of intermittent hypoxia on ferrous citrate (iron)-induced oxidative stress was investigated in the nigrostriatal dopaminergic system of rat brain. Female Wistar rats were subjected to 380 mm Hg in an altitude chamber for 15 h/day for 7, 14, or 28 days. Iron was locally infused in the substantia nigra of anesthetized rats. Seven days after infusion, lipid peroxidation was elevated in the infused substantia nigra and dopamine content and tyrosine hydroxylase-positive axons were decreased in the ipsilateral striatum in the normoxic rats. Intermittent hypoxic treatment prevented iron-induced oxidative injuries. Induction of the neuroprotection required 2 weeks. Intracerebroventricular infusion of l-buthionine-[S,R]-sulfoximine (L-BSO), which mimicked a reduced antioxidative condition, aggravated iron-induced oxidative injuries. Intermittent hypoxia ameliorated L-BSO-induced augmentation of iron-induced oxidative injuries. Basal GSH (glutathione) content, GSH/GSSG ratio, superoxide dismutase (SOD) and catalase activities in intact substantia nigra were not altered by intermittent hypoxia. Furthermore, intermittent hypoxia attenuated iron-induced reductions in GSH content, GSH/GSSG ratio, and SOD, iron-induced increase in catalase but had no effect on glutathione peroxidase. Our data suggest that intermittent hypoxia may protect the nigrostriatal dopaminergic system from iron-induced oxidative injuries. Moreover, antioxidative defensive systems may partially contribute to the neuroprotection by intermittent hypoxia.