Increased ferric iron content and iron-induced oxidative stress in the brains of scrapie-infected mice

Redox Control of Prion and Disease Pathogenesis

“…Markers of metal-induced oxidative stress such as products of lipid peroxidation, including free malondialdehyde (MDA) and increased levels of Fe 2þ and Fe 3þ ions, have been identified in the cerebral cortex, striatum, and brainstem of prion disease-affected human and mouse brains, supporting this assumption (5,108,109,111,171,203). The state of increased oxidative stress could result from direct toxicity by PrP-metal complexes, increased susceptibility of neuronal cells to free radicals due to the compromised function of PrP C , or a combination of both processes (22,140,141,182).…”

“…The underlying mechanism leading to the development of protein aggregates and accompanying neurotoxicity is relatively clear for some of these conditions, whereas in others, it is still debated. Recent evidence suggests the imbalance of brain metal homeostasis as a common cause of neuronal death in several of these disorders (9,45,48,60,61,70,111,148,171,203,242). It is believed that a redox-active metal interacts with a specific protein and is reduced in its presence, resulting in the generation of reactive oxygen species (ROS), hydrogen peroxide (H 2 O 2 ), and hydroxyl radicals (OH ) that cause aggregation of the involved protein (16,206,215,224,225).…”

Interactions between Infections, Nutrients and Xenobiotics

“…In the brain there is a concomitant accumulation of Se and Hg (Ilbäck et al, 2005a), as well as an increased content of Cu (Ilbäck et al, 2004b). An increased Fe accumulation is also known to occur in the liver in human hepatitis C virus infection (Weiss, 2002), in the brain of HIV-infected humans (Boelaert et al, 1996), in the brain of scrapie-infected mice (Kim et al, 2000), and in human sclerotic cardiac valves that harbour C. pneumoniae (NystromRosander et al, 2003).…”

“…These trace elements are crucial for the host defence (Beisel, 1998;Pekarek and Engelhardt, 1981), including the development of inflammation (Milanino et al, 1993;Pekarek and Engelhardt, 1981). All changes in trace elements, however, may not be favourable for the host (Weiss, 2002), such as the progressive increase of Fe in the brain during scrapie infection in mice (Kim et al, 2000) and in HIV infection in man (Boelaert et al, 1996). Furthermore, many bacteria need Fe for their growth and multiplication and excessive Fe in specific tissues has been shown to promote bacterial infection in those tissues (Al-Younes et al, 2001;Foster et al, 2001;Lounis et al, 2001;Weiss, 2002).…”

“…In CBV infection mortality and inflammatory lesions in the heart were not increased by dietary Cd exposure (Ilback et al, 1994b), but Cd exposure resulted in increased Cu and Fe concentrations in the brain, where Fe was accumulated in focal deposits (Ilback et al, 2005b). Fe accumulation in the brain is also known to occur in HIV patients (Boelaert et al, 1996) and in scrapie-infected animals (Kim et al, 2000).…”