Effects of a direct injection of liposoluble iron into rat striatum. Importance of the rate of iron delivery to cells.
For a better understanding of the role of iron imbalance in neuropathology, a liposoluble iron complex (ferric hydroxyquinoline, FHQ) was injected into striatum of rats. The effects of two modalities of iron injections on brain damage, hydroxyl radical (*OH) production (assessed by the salicylate method coupled to microdialysis) and tissue reactive iron level (evaluated ex vivo by the propensity of the injected structure for lipid peroxidation) were examined. Rapid injection of FHQ (10 nmoles of 5 mM FHQ pH 3 solution over 1-min period) but not that of corresponding vehicle led to extensive damage associated with increased tissue free iron level in the injected region. Conversely, neither lesion nor free iron accumulation was observed after slow FHQ injection (10 nmoles of a 100 microM FHQ pH 7 solution over 1-h period) as compared to corresponding vehicle injection. Production of *OH was induced by slow FHQ injection but not by rapid FHQ injection, probably as a result of in vivo abolition of iron-induced *OH formation by acid pH. Indeed, rapid injection of FAC pH 7 (ferric ammonium citrate, 5 mM in saline) was associated with *OH formation whereas rapid injection of FAC pH 3 did not. Our results identify the rate of iron delivery to cells as an important determinant of iron toxicity and do not support a major role for extracellular *OH in damage associated with intracerebral iron injection.
Demougeot
C
C
Laboratoire de Pharmacodynamie, BP 87900, Faculté de Pharmacie, 21079 Dijon, France.
Méthy
D
D
Prigent-Tessier
A
A
Garnier
P
P
Bertrand
N
N
Guilland
J C
JC
Beley
A
A
Marie
C
C
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D005290:Ferric Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000633:toxicity; D017665:Hydroxyl Radical / Q000378:metabolism; D006912:Hydroxyquinolines / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000633:toxicity; D007267:Injections; D007501:Iron / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000633:toxicity; D015227:Lipid Peroxidation; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility
D005290:Ferric Compounds; D006912:Hydroxyquinolines; C097920:ferric 8-hydroxyquinoline; D017665:Hydroxyl Radical; D007501:Iron; D001058:Apomorphine