title: Changes in uptake of vitamin B(12) and trace metals in brains of mice treated with clioquinol.
abstract: Clioquinol is a hydroxyquinoline antibiotic that has been associated with severe side-effects in the CNS. The syndrome caused by clioquinol treatment, subacute myelo-optic neuropathy (SMON), is considered as one of the worst drug disasters of this century. The precise biochemical mechanism behind SMON is not fully understood. Clioquinol can form strong lipophilic chelates with divalent cations and therefore it has been speculated that the drug may disturb the retention of vitamin B(12) through chelation of Co(2+). In the present study, the tissue distribution and uptake capacity of [57Co]cyanocobalamin were estimated in mice treated with clioquinol or saline. The concentrations of some trace metals were also determined in brain tissue. Accumulation of vitamin B(12) in the brain and its concentration in blood were decreased by clioquinol treatment. The mean concentrations of several trace metals were also lowered in the brain while the concentration of cobalt in the brain was not affected, suggesting that clioquinol does not bind to the cobalt in vitamin B(12). Moreover, a significant decrease in the levels of S-adenosylmethionine (SAM) was observed in the brain after clioquinol treatment. This may be a consequence of decreased vitamin B(12) levels. From these results, it can be concluded that chronic treatment with clioquinol may alter the tissue homeostasis of vitamin B(12) in the brain.
authors.affiliation: Department of Neuroscience, Unit of Pharmacology, Biomedical Center, University of Uppsala, Uppsala, Sweden.
authors.forename: M S
authors.initials: MS
authors.lastname: Yassin
authors.forename: J
authors.initials: J
authors.lastname: Ekblom
authors.forename: M
authors.initials: M
authors.lastname: Xilinas
authors.forename: C G
authors.initials: CG
authors.lastname: Gottfries
authors.forename: L
authors.initials: L
authors.lastname: Oreland
mesh_terms: D000563:Amebicides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D007464:Clioquinol / Q000378:metabolism*; D008297:Male; D008670:Metals / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D009901:Optic Nerve Diseases / Q000378:metabolism; D012435:S-Adenosylhomocysteine / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000378:metabolism; D014131:Trace Elements / Q000378:metabolism*; D014805:Vitamin B 12 / Q000378:metabolism*
chemical_list: D000563:Amebicides; D008670:Metals; D014131:Trace Elements; D007464:Clioquinol; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; D014805:Vitamin B 12