Diethyldithiocarbamate and brain copper.
To test the hypothesis that the increase of copper concentration in brain after diethyldithiocarbamate (DEDTC) administration was due to the formation of a DEDTC-copper complex, able to cross the blood-brain barrier, we compared in rats the effects on brain copper of DEDTC given alone, in combination with copper or as a copper-DEDTC complex. The daily administration for three weeks of DEDTC alone, of DEDTC with copper and DEDTC-copper complex gave the same increase of the level of copper in brain. The time course effects of a single administration of DEDTC and of the DEDTC-copper complex were approximately the same: after a delay of about 24 h, there was an increase in brain copper concentrations which persisted for at least three days. This delayed effect explains discrepancies found in the literature concerning changes of copper in brain after a single administration of DEDTC according to the time interval between administration and tissue sampling. The results show that the additional copper does not increase the effect of DEDTC and that the formation of a DEDTC-copper lipophilic complex which could cross the blood-brain barrier is probably not the mechanism responsible for the increase of brain copper induced by DEDTC. Mechanisms other than direct copper chelation may be involved.
Laboratoire de Pharmacologie et Toxicologie, Centre Hospitalier Universitaire, Angers, France.
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Allain
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Krari
D000284:Administration, Oral; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003300:Copper / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D004050:Ditiocarb / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D004338:Drug Combinations; D007274:Injections, Intraperitoneal; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D004338:Drug Combinations; D003300:Copper; D004050:Ditiocarb