title: Manganese-induced hydroxyl radical formation in rat striatum is not attenuated by dopamine depletion or iron chelation in vivo.
abstract: The present studies were aimed at investigating the possible roles of dopamine (DA) and iron in production of hydroxyl radicals (OH) in rat striatum after Mn2+ intoxication. For this purpose, DA depletions were assessed concomitant with in vivo 2,3- and 2,5-dihydroxybenzoic acid (DHBA) formation from the reaction of salicylate with OH, of which 2,3-DHBA is a nonenzymatic adduct. Following intrastriatal Mn2+ injection, marked 2,3-DHBA increases were observed in a time- and dose-dependent fashion reaching maximum levels at 6-18 h and a plateau beyond 0.4 micromol (fourfold increase). The delayed increase of 2,3-DHBA levels suggestS that Mn2+ induces OH formation in the living brain by an indirect process. The early DA depletion (2 h) and relatively late OH formation (6 h) indicate independent processes by Mn2+. In addition, depletion of DA (about 90%) by reserpine pretreatment not significantly alter Mn2+-induced 2,3-DHBA formation or the extent of DA depletion, suggesting that DA or DA autoxidation are not participating in Mn2+-induced OH formation in vivo. Furthermore, Mn2+ injection did not significantly alter the low molecular weight weight iron pool in striatum, and co-injections of the iron-chelator deferoxamine with Mn(2+) into striatum did not significantly attenuate Mn(2+)-induced 2,3-DHBA formation. These findings suggest no role of chelatable iron in generation of Mn(2+)-induced OH, but do not exclude a role for mitochondrial heme-iron or peroxynitrite (Fe-indepeNdent) in Mn2+-induced OH formation.
authors.affiliation: TNO Nutrition and Ffood Research Institute, Department of Bio-pharmaceutical Analysis, Zeist, The Netherlands.
authors.forename: W N
authors.initials: WN
authors.lastname: Sloot
authors.forename: J
authors.initials: J
authors.lastname: Korf
authors.forename: J F
authors.initials: JF
authors.lastname: Koster
authors.forename: L E
authors.initials: LE
authors.lastname: De Wit
authors.forename: J B
authors.initials: JB
authors.lastname: Gramsbergen
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003676:Deferoxamine / Q000494:pharmacology; D004298:Dopamine / Q000172:deficiency*; D004305:Dose-Response Relationship, Drug; D017665:Hydroxyl Radical / Q000378:metabolism*; D007501:Iron / Q000737:chemistry / Q000378:metabolism; D007502:Iron Chelating Agents / Q000494:pharmacology*; D008297:Male; D008345:Manganese / Q000494:pharmacology*; D008970:Molecular Weight; D009498:Neurotoxins / Q000494:pharmacology; D009994:Osmolar Concentration; D016627:Oxidopamine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012110:Reserpine / Q000494:pharmacology; D013997:Time Factors
chemical_list: D007502:Iron Chelating Agents; D009498:Neurotoxins; D017665:Hydroxyl Radical; D008345:Manganese; D012110:Reserpine; D016627:Oxidopamine; D007501:Iron; D003676:Deferoxamine; D004298:Dopamine