Transmethylation Reactions and Autoradiographic Distribution of Vitamin B_<12> : Effects of Clioquinol Treatment in Mice

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Author(s)

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 B<SUB>12</SUB> through chelation of Co<SUP>2+</SUP>. In the present paper, possible effects of clioquinol on the uptake and tissue distribution of [<SUP>57</SUP>Co]-cyanocobalamin have been studied in mice. In vivo experiments showed markedly decreased accumulation of radiolabelled vitamin B<SUB>12</SUB> in the kidney and skin in animals that were pre-treated with clioquinol. The chloroform:water partition coefficients for [<SUP>57</SUP>Co]-cyanocobalamin in the presence or absence of clioquinol were also determined. No statistically significant alterations in the partition coefficient for [<SUP>57</SUP>Co]-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 <I>S</I>-adenosylhomocysteine levels were not affected. In contrast, clioquinol treatment caused a significant increase in the levels of <I>S</I>-adenosylmethionine in the brain. The data of the present study show that clioquinol treatment can affect the accumulation of vitamin B<SUB>12</SUB> 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 B<SUB>12</SUB>.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 78(1), 55-61, 1998-09

    The Japanese Pharmacological Society

References:  23

Codes

  • NII Article ID (NAID)
    10008193745
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    00215198
  • NDL Article ID
    4565703
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  NDL  J-STAGE 
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