Oxidative stress and damage in liver, but not in brain, of Fischer 344 rats subjected to dietary iron supplementation with lipid-soluble [(3,5,5-trimethylhexanoyl)ferrocene].
Accumulation of iron probably predisposes the aging brain to progressive neuronal loss. We examined various markers of oxidative stress and damage in the brain and liver of 3- and 24-month-old rats following supplementation with the lipophilic iron derivative [(3,5,5-trimethylhexanoyl)ferrocene] (TMHF), which is capable of crossing the blood-brain barrier. At both ages, iron concentration increased markedly in the liver but failed to increase in the brain. In the liver of TMHF-treated young rats, levels of alpha- and gamma-tocopherols and glutathione (GSH) were also higher. In contrast, the brain displayed unaltered levels of the tocopherols and GSH. Malondialdehyde (MDA) level was also higher in the cerebrospinal fluid (CSF) and the liver but not in the brain. In old rats, the absence of an increase in iron concentration in the brain was reflected by unaltered concentrations of GSH, tocopherols, and MDA as compared to that in untreated rats. In the aging liver, concentrations of GSH and MDA increased with TMHF treatment. Morphological studies revealed unaltered levels of iron, ferritin, heme oxygenase-1 (HO-1), nitrotyrosine (NT), or MDA in the brains of both young and old rats treated with TMHF. In contrast, TMHF treatment increased the level of HO-1 in Kupffer cells, NT in hepatic endothelial cells, and MDA and ferritin in hepatocytes. Although these results demonstrated an increase in the biochemical markers of oxidative stress and damage in response to increasing concentrations of iron in the liver, they also demonstrated that the brain is well protected against dietary iron overload by using iron in a lipid-soluble formulation.
Lykkesfeldt
Jens
J
Section of Biomedicine, Department of Veterinary Pathobiology, University of Copenhagen, Denmark.
Morgan
Evan
E
Christen
Stephan
S
Skovgaard
Lene Theil
LT
Moos
Torben
T
D000821:Animal Feed; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D019587:Dietary Supplements; D005296:Ferrous Compounds / Q000737:chemistry* / Q000633:toxicity*; D007501:Iron / Q000493:pharmacokinetics / Q000633:toxicity*; D008055:Lipids / Q000737:chemistry*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D000075163:Metallocenes; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344; D012995:Solubility
D005296:Ferrous Compounds; D008055:Lipids; D000075163:Metallocenes; C050224:3,5,5-trimethylhexanoylferrocene; D007501:Iron