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Modulation of oxidative events by multivalent manganese complexes in brain tissue
D HaMai1, A Campbell, S C Bondy
1Department of Community and Environmental Medicine, Center for Occupational and Environmental Health, University of California, Irvine, Irvine, CA 92697-1825, USA. diemh@uci.edu
Free Radical Biology & Medicine
|September 15, 2001
Summary
Manganese
Area of Science:
- Neuroscience
- Toxicology
- Biochemistry
Background:
- Manganese toxicity causes neuropsychiatric and neuromotor issues, often linked to oxidative stress in the dopaminergic system.
- Manganese's role as a pro-oxidant is debated due to conflicting reports of both pro- and antioxidant properties.
Purpose of the Study:
- To resolve conflicting findings regarding the oxidative properties of manganese.
- To investigate the role of trace trivalent metals in manganese-induced reactive oxygen species (ROS) generation.
Main Methods:
- Utilized a cortical mitochondrial-synaptosomal (P2) fraction to assess manganese's effect on ROS formation.
- Employed desferroxamine (DFO), a trivalent metal chelator, to investigate the mechanism of ROS generation.
- Differentiated the effects of trace ferric and manganic ions on ROS production.
Main Results:
- Desferroxamine (DFO) completely inhibited manganese-induced ROS generation, suggesting the involvement of a trace trivalent metal.
- Manganic ion, not ferric ion, significantly enhanced ROS generation attributed to divalent manganese.
- Trace amounts of trivalent cations profoundly influence Mn2+-related free radical generation.
Conclusions:
- The controversial oxidative properties of manganese are explained by the potent influence of trace amounts of trivalent metal ions, specifically manganic ion.
- This study clarifies the mechanism behind manganese-induced oxidative stress, resolving prior discrepancies in the literature.