High doses of cobalt induce optic and auditory neuropathy.
The adverse biological effects of continuous exposure to cobalt and chromium have been well defined. In the past, this toxicity was largely an industrial issue concerning workers exposed in occupational setting. Nevertheless, recent reports have described a specific toxicity mediated by the high levels of cobalt and chromium released by metallic prostheses, particularly in patients who had received hip implants. Clinical symptoms, including blindness, deafness and peripheral neuropathy, suggest a specific neurotropism. However, little is known about the neuropathological basis of this process, and experimental evidence is still lacking. We have investigated this issue in an experimental setting using New Zealand White rabbits treated with repeated intravenous injections of cobalt and chromium, alone or in combination. No evident clinical or pathological alterations were associated after chromium administration alone, despite its high levels in blood and tissue while cobalt-chromium and cobalt-treated rabbits showed clinical signs indicative of auditory and optic system toxicity. On histopathological examination, the animals showed severe retinal and cochlear ganglion cell depletion along with optic nerve damage and loss of sensory cochlear hair cells. Interestingly, the severity of the alterations was related to dosages and time of exposure. These data confirmed our previous observation of severe auditory and optic nerve toxicity in patients exposed to an abnormal release of cobalt and chromium from damaged hip prostheses. Moreover, we have identified the major element mediating neurotoxicity to be cobalt, although the molecular mechanisms mediating this toxicity still have to be defined.
Department of Experimental and Applied Medicine, Section of Occupational Health and Industrial Hygiene, University of Brescia, Italy.
Pietro
P
Apostoli
Simona
S
Catalani
Anna
A
Zaghini
Andrea
A
Mariotti
Pietro Luigi
PL
Poliani
Valentina
V
Vielmi
Francesco
F
Semeraro
Sarah
S
Duse
Andrea
A
Porzionato
Veronica
V
Macchi
Alessandro
A
Padovani
Maria Cristina
MC
Rizzetti
Raffaele
R
De Caro
D000818:Animals; D002712:Chlorides / Q000493:pharmacokinetics / Q000633:toxicity; D017608:Chromium Compounds / Q000493:pharmacokinetics / Q000633:toxicity; D003035:Cobalt / Q000493:pharmacokinetics / Q000633:toxicity*; D003051:Cochlea / Q000000981:diagnostic imaging / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D006313:Hearing Loss, Central / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D020260:Heavy Metal Poisoning, Nervous System / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D009900:Optic Nerve / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits; D012160:Retina / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D012584:Sciatic Nerve / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D014018:Tissue Distribution; D014463:Ultrasonography
D002712:Chlorides; D017608:Chromium Compounds; D003035:Cobalt; C017133:chromous chloride; C018021:cobaltous chloride