Transmethylation reactions and autoradiographic distribution of vitamin B12: effects of clioquinol treatment in mice.
The catastrophic epidemic of subacute myelo-optic neuropathy (SMON) affected Japan around 1970 with thousands of victims. The cause was attributed to high doses of locally acting oxyquinolines. It has been speculated that oxyquinoline derivatives of the clioquinol type can disturb the retention of vitamin B12 through chelation of Co2+. In the present paper, possible effects of clioquinol on the uptake and tissue distribution of [57Co]-cyanocobalamin have been studied in mice. In vivo experiments showed markedly decreased accumulation of radiolabelled vitamin B12 in the kidney and skin in animals that were pre-treated with clioquinol. The chloroform:water partition coefficients for [57Co]-cyanocobalamin in the presence or absence of clioquinol were also determined. No statistically significant alterations in the partition coefficient for [57Co]-cyanocobalamin in the presence of clioquinol was evident, indicating that clioquinol does not bind cobalt. In addition, transmethylation reactions in the CNS in mice treated with clioquinol were studied. Specific activities of methionine adenosyltransferase, and S-adenosylhomocysteine levels were not affected. In contrast, clioquinol treatment caused a significant increase in the levels of S-adenosylmethionine in the brain. The data of the present study show that clioquinol treatment can affect the accumulation of vitamin B12 in the kidney and the skin but not in the brain. These results do not support the hypothesis that clioquinol causes its damage to the nervous system by a direct chemical interaction with vitamin B12.
Yassin
M S
MS
Department of Neuroscience (Pharmacology), Biomedical Center, Uppsala University, Sweden.
Ekblom
J
J
Löfberg
C
C
Oreland
L
L
D000818:Animals; D000891:Anti-Infective Agents, Local / Q000494:pharmacology; D001345:Autoradiography; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002725:Chloroform / Q000737:chemistry; D007464:Clioquinol / Q000494:pharmacology; D003037:Cobalt Radioisotopes; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008716:Methionine Adenosyltransferase / Q000187:drug effects / Q000378:metabolism; D008745:Methylation / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D012435:S-Adenosylhomocysteine / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000187:drug effects / Q000378:metabolism; D012588:Scintillation Counting; D012995:Solubility / Q000187:drug effects; D014018:Tissue Distribution; D014805:Vitamin B 12 / Q000032:analysis / Q000378:metabolism / Q000493:pharmacokinetics*; D014867:Water / Q000737:chemistry
D000891:Anti-Infective Agents, Local; D003037:Cobalt Radioisotopes; D014867:Water; D007464:Clioquinol; D012436:S-Adenosylmethionine; D002725:Chloroform; D012435:S-Adenosylhomocysteine; D008716:Methionine Adenosyltransferase; D014805:Vitamin B 12