The lipophilic iron compound TMH-ferrocene [(3,5,5-trimethylhexanoyl)ferrocene] increases iron concentrations, neuronal L-ferritin, and heme oxygenase in brains of BALB/c mice.
Mismanagement of intracellular iron is a key pathological feature of many neurodegenerative diseases. Our long-term goal is to use animal models to investigate the mechanisms of iron neurotoxicity and its relationship to neurodegenerative pathologies. The immediate aim of this experiment was to determine regional distribution of iron and cellular distribution of iron storage proteins (L- and H-ferritin) and an oxidative stress marker (heme oxygenase-1) in brains of mice fed the lipophilic iron compound (3,5,5-trimethylhexanoyl) (TMH)-ferrocene. We fed male and female weanling BALB/cj mice diets either deficient in iron (0 mg Fe/kg diet), adequate in iron (35 mg Fe/kg diet; control mice), or adequate in iron and supplemented with 0.1 or 1.0 g TMH-ferrocene/kg diet for 8 wk. Iron concentrations in cerebrum were higher in mice fed 1.0 g TMH-ferrocene/kg diet than in control mice (p < 0.05). Liver iron concentrations were eightfold higher in mice fed 1.0 g TMH-ferrocene/kg diet than in control mice (p < 0.0001). L-Ferritin and heme oxygenase-1 expression were elevated in striatum in mice fed 1.0 g TMH-ferrocene/kg diet. We conclude that administration of the lipophilic iron compound TMH-ferrocene leads to subtle perturbations of cellular iron within the brain, potentially representing a model of iron accumulation similar to that seen in various neuropathological conditions.
Malecki
Elise A
EA
Department of Neuroscience and Anatomy, College of Medicine, The Pennsylvania State University, Hershey 17033, USA.
Cable
Edward E
EE
Isom
Harriet C
HC
Connor
James R
JR
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005293:Ferritins / Q000032:analysis*; D005296:Ferrous Compounds / Q000633:toxicity*; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D007150:Immunohistochemistry; D007501:Iron / Q000378:metabolism*; D008297:Male; D000075163:Metallocenes; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000737:chemistry*; D013194:Staining and Labeling
D005296:Ferrous Compounds; D000075163:Metallocenes; C050224:3,5,5-trimethylhexanoylferrocene; D005293:Ferritins; D007501:Iron; D006419:Heme Oxygenase (Decyclizing)