Effect of sodium pyridinethione on the uptake and distribution of nickel in rats, ferrets and guinea-pigs.
Oral administration of sodium pyridinethione together with Ni2+ (using 63Ni2+ as a tracer) to rats, ferrets and guinea-pigs produced highly increased tissue levels of the metal in several tissues in comparison with animals given the Ni2+ alone. Ni2+ forms a lipophilic complex with pyridinethione and it can be assumed that a facilitated passage of the Ni2+ across the cellular membranes of various tissues is important for the observed effects. Pigmented tissues (e.g. the eye melanin), the pancreatic islets, the nervous system and striated muscles showed high levels of Ni2+ in animals given sodium pyridinethione. However, in some instances marked species differences were observed. Thus, microautoradiography indicated an uptake of Ni2+ both in the beta- and alpha-cells in the pancreatic islets in the rat, whereas in the guinea-pig only some cells (probably the alpha-cells) accumulated high levels of Ni2+. In the ferret sodium pyridinethione induced a high uptake of Ni2+ in the heart muscle, which was not seen in the other species. The Ni2+ is probably taken up in the various tissues complexed to pyridinethione. Within the tissues the complex may dissociate and the Ni2+ may bind to some endogenous tissue components. The affinity of the Ni2+ for the endogenous ligands in relation to the affinity for the pyridinethione may be of importance for the effects on the disposition of the Ni2+. The species variations may be related to differences in the structural conformations of the endogenous Ni(2+)-binding ligands.
Swedish University of Agricultural Sciences, Faculty of Veterinary Medicine, Department of Pharmacology and Toxicology, Biomedicum, Uppsala.
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Tjälve
D000818:Animals; D001345:Autoradiography; D005260:Female; D005289:Ferrets; D006168:Guinea Pigs; D009532:Nickel / Q000493:pharmacokinetics*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D012588:Scintillation Counting; D013871:Thiones; D014018:Tissue Distribution
D011725:Pyridines; D013871:Thiones; C008704:pyrithione; D009532:Nickel