Uptake of 63Ni2+ in the central and peripheral nervous system of mice after oral administration: effects of treatments with halogenated 8-hydroxyquinolines.
Oral administration of 63Ni2+ to mice resulted in higher levels of the metal in the sciatic nerves, the trigeminal ganglia, spinal nerve roots and the spinal cord than in the cerebellum and the frontal cortex. In the sciatic nerves, the trigeminal ganglia and the spinal nerve roots a high vascular permeability may explain the preferential uptake of the 63Ni2+. The higher accumulation of the 63Ni2+ in the spinal cord than in the examined structures of the brain may be related to a diffusion from the cerebrospinal fluid. Administrations of halogenated 8-hydroxyquinolines [5,7-diiodo-8-hydroxyquinoline (diI-HQ), 5,7-dibromo-8-hydroxyquinoline (diBr-HQ), 5,7-dichloro-8-hydroxyquinoline (diCl-HQ) or 5-chloro-7-iodo-8-hydroxyquinoline (Cl-I-HQ)] together with the 63Ni2+ resulted in increased levels of the metal both in neural and extraneural tissues in comparison with mice given the 63Ni2+ alone. In most instances the tissue-levels of 63Ni2+ were 2-4 times higher in the animals treated with the halogenated 8-hydroxyquinolines than in the controls. Determinations of chloroform/water partition coefficients showed that lipophilic chelates are formed between each of these compounds and the nickel. Our results are probably explained by a facilitated passage of the complexed metal over the walls of the stomach and the intestine. The halogenated 8-hydroxyquinolines are linked with the SMON-syndrome, a disease which occurred primarily in Japan. The possibility that this syndrome may be causally connected with a concomitant intake of these drugs and metals is discussed.
Borg
K
K
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala.
Tjälve
H
H
D000284:Administration, Oral; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism*; D004347:Drug Interactions; D005260:Female; D006846:Hydrocarbons, Halogenated / Q000494:pharmacology*; D006912:Hydroxyquinolines / Q000494:pharmacology*; D051379:Mice; D009532:Nickel / Q000493:pharmacokinetics* / Q000633:toxicity; D010525:Peripheral Nerves / Q000187:drug effects / Q000378:metabolism*; D011868:Radioisotopes; D014018:Tissue Distribution
D006846:Hydrocarbons, Halogenated; D006912:Hydroxyquinolines; D011868:Radioisotopes; D009532:Nickel