Pharmacology of Lazaroids and Brain Energy Metabolism: A Review
1. Roberto Federico VillaFNa and
2. Antonella Gorini
+ Author Affiliations
Institute of Pharmacology, Faculty of Science, University of Pavia, Pavia, Italy
A considerable body of experimental evidence indicates that lipid peroxidation (Komara et al., 1986; Dexter et al., 1989), the presence of iron (Riederer et al., 1989; Hirsh et al., 1991) and the depletion of natural antioxidants (Sato and Hall, 1992) seem to be a common epiphenomena of some pathologies in the central nervous system (CNS).b
The role of iron (either free or complexed) in catalyzing oxygen-derived free radical production and, consequently, its role in the peroxidative process (Halliwell and Gutteridge, 1984; Braughler et al., 1986; Minotti and Aust, 1989) is well known, even though the involvement of this biochemical pathway with the pathogenesis of some neuropathologies remains unclear.
The radical-initiated peroxidation of neuronal, glial, vascular cell membranes and myelin is catalyzed by free iron released from hemoglobin, transferrin and ferritin by either lowered tissue pH or oxygen radicals. If unchecked, lipid peroxidation is a geometrically progressing process that will spread over the surface of the cell membrane, causing impairment to phospholipid-dependent enzymes, disruption of ionic gradients and, if severe enough, membrane lysis.
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