title: Oxidative changes in the rat brain by intraperitoneal injection of ferric nitrilotriacetate.
abstract: Iron is known to be involved in neuronal diseases such as neurodegenerative diseases, brain ischemia and epilepsy. However, it is unclear if a high level of peripheral iron induces these pathological conditions. Since ferric nitrilotriacetate (Fe-NTA), a low molecule iron chelate, causes kidney carcinoma and diabetes in animals due to its strong and unique oxidative stress, it is also considered to cause pathological conditions in the brain. Therefore, we studied brain changes after intraperitoneal (i.p.) injection of Fe-NTA. We investigated iron distribution in the brain and evaluated heme oxygenase (HO)-1 mRNA, IL-6 mRNA and 4-hydroxy-2-nonenal (4-HNE) quantitatively. In addition, changes in muscarinic acetylcholine receptor mRNAs were measured. It was found that iron was localized in the cortex and the hypothalamus, but not in other areas of the brain. HO-1 was induced in both the cortex and hypothalamus, and the levels of IL-6 and 4-HNE were raised in the hypothalamus, but not in the cortex. In the cortex, expression in M1 and M2 mAChRs were suppressed. In conclusion, iron reached the brain parenchyma after i.p. injection of Fe-NTA, and Fe-NTA caused oxidative reactions and suppression of mAChRs in the brain.
authors.affiliation: Department of Dental Anesthesiology, Okayama University Hospital, Okayama, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Nakatsuka
authors.forename: Shigeru
authors.initials: S
authors.lastname: Maeda
authors.forename: Tsugunobu
authors.initials: T
authors.lastname: Andoh
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Mizuno
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Higuchi
authors.forename: Takuya
authors.initials: T
authors.lastname: Miyawaki
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D005290:Ferric Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics; D006651:Histocytochemistry; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D015151:Immunoblotting; D007274:Injections, Intraperitoneal; D015850:Interleukin-6 / Q000235:genetics; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009571:Nitrilotriacetic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D016133:Polymerase Chain Reaction; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000447:Aldehydes; D005290:Ferric Compounds; D015850:Interleukin-6; D007502:Iron Chelating Agents; D007501:Iron; D006419:Heme Oxygenase (Decyclizing); C027576:4-hydroxy-2-nonenal; D009571:Nitrilotriacetic Acid; C020326:ferric nitrilotriacetate