Effects of a Direct Injection of Liposoluble Iron into Rat Striatum. Importance of the Rate of Iron Delivery to Cells

Abstract

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.

Genotoxic effects of aluminum, iron and manganese in human cells and experimental systems: A review of the literature

“…74 Furthermore, ROS interacts with a variety of molecules, including in saturated fatty acids, proteins and DNA leading to subsequent cell death/apoptosis, especially in the CNS tissue, where the antioxidant defenses are rare. [75][76][77] Taking all together, all those mechanisms may explain all those effects and the concomitance occurrence of mutagenicity and cytotoxicity.…”

Alzheimer’s Disease and Metal Contamination: Aspects on Genotoxicity

“…Free iron catalyzes the conversion of superoxide and hydrogen peroxide into hydroxyl radicals, which promote oxidative stress by the Fenton reaction (Berg et al, 2001). Furthermore, ROS interacts with a variety of molecules, including unsaturated fatty acids, proteins and DNA leading to subsequent cell death/apoptosis, especially on CNS tissue, whereas the antioxidant defenses are rare (Demougeot et al, 2003;Stankiewicz & Brass, 2009;Willmore & Rubin, 1984). Thus, disturbances of brain iron homeostasis have been linked to acute neuronal injury leading to neurodegenerative disorders (Campbell & Bondy, 2000;Montgomery, 1995) such as Alzheimer's (AD), Parkinson's (PD), and Huntington's (HD) diseases as well as amyotrophic lateral sclerosis (ALS) (Connor & Benkovic, 1992;Kell, 2010;Liu et al, 2006;Rouault, 2001;Youdim et al, 2005).…”