Mohammed S. Yassin, Jonas Ekblom, Charlotta Lofberg and Lars Oreland
(*)
Department of Neuroscience (Pharmacology), Biomedical Center, Uppsala
University, Box 593, S-751 24 Uppsala, Sweden
(*) To whom correspondence should be addressed.
Abstract: 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.
Keywords: S-Adenosylmethionine, L-Methionine S-adenosyltransferase, Clioquinol,
Vitamin B12, Subacute myelo-optic neuropathy (SMON)