Cadmium-metallothionein interactions in the olfactory pathways of rats and pikes.
Deposition of cadmium onto the olfactory epithelium results in transport of the metal along the primary olfactory neurons to the olfactory bulbs of the brain. The present investigation was undertaken to determine the intracellular ligand binding of cadmium during this process. (109)Cd(2+) was applied on the olfactory epithelium of rats and pikes, and the subcellular distribution of the metal in the olfactory pathways was then examined. Two groups of rats were used: one pretreated with intranasal instillations of nonlabeled cadmium and the other given physiological saline (controls). Cellular fractionations showed that the (109)Cd(2+) was predominantly present in the cytosol of all samples, both in the rats and the pikes. Gel filtrations of the olfactory epithelium of control rats killed 2 h after the (109)Cd(2+) instillation showed that the metal was recovered in two peaks with elution volumes corresponding to metallothionein (MT) and glutathione (GSH)-the latter peak being the predominant one. However, in the epithelium of the cadmium-pretreated rats killed at 2 h, (109)Cd(2+) was recovered in one peak corresponding to MT. In the olfactory epithelium and bulbs of both groups of rats killed at 48 h, as well as in the olfactory epithelium, nerves, and bulbs of pikes killed at this interval, (109)Cd(2+) was recovered in one peak corresponding to MT. Immunohistochemistry of the olfactory system of rats given cadmium in the right nasal cavity showed induction of MT in the neuronal, sustentacular, and basal cells of the right olfactory epithelium, in the nerve fascicles in the lamina propria of the right olfactory mucosa, and in the olfactory nerve layer of the right olfactory bulb. On the left side, the immunoreactivity was low in these structures. MT immunoreactivity was observed in the glomeruli of both the right and the left olfactory bulbs. However, the staining was homogeneously distributed within the entire glomeruli of the right bulb, whereas it showed a mesh-like pattern corresponding to the localization of astrocytes in the glomeruli of the left bulb. We conclude that exposure of the olfactory epithelium to cadmium results in induction of MT in the primary olfactory neurons and a transport of the metal in these neurons as a cadmium-metallothionein (CdMT) complex. Our results further indicate that GSH is a ligand that can interact with cadmium before the metal binds to MT.
Tallkvist
Jonas
J
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala Biomedical Center, Box 573, SE-751 23 Uppsala, Sweden. jonas.tallkvist@farmtox.slu.se
Persson
Eva
E
Henriksson
Jörgen
J
Tjälve
Hans
H
D000281:Administration, Intranasal; D000818:Animals; D001692:Biological Transport; D002104:Cadmium / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*; D002106:Cadmium Radioisotopes; D002458:Cell Fractionation; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D017859:Esocidae; D007124:Immunoenzyme Techniques; D008297:Male; D008668:Metallothionein / Q000378:metabolism*; D009830:Olfactory Bulb / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D002106:Cadmium Radioisotopes; D002104:Cadmium; D008668:Metallothionein