Cisplatin-induced hearing loss does not correlate with intracellular platinum concentration.
CONCLUSIONS
Inductively coupled plasma mass spectrometry (ICP-MS) can be applied to organic tissues obtained from experimental animals. Hearing loss does not correlate with the platinum (Pt) concentration found in the inner ear. Drug structure and affinity to inner ear proteins could explain ototoxicity caused by cisplatin.


OBJECTIVE
To analyse Pt affinity for brain and ear tissues (of similar embryologic origin) in the Wistar rat and clearance gradient after a single dose, and to correlate these findings with hearing changes.


METHODS
Thirty-two Wistar rats were intraperitoneally injected with cisplatin at a dose of 5 mg/kg. Animals were sacrificed after obtaining auditory brain responses (ABRs) at 3, 7, 30 and 90 days (nine, seven, seven and nine animals, respectively). Brain and both temporal bones were extracted from each animal and analysed by ICP-MS to determine the absolute concentrations of the metal. Eight non-treated animals were employed as a control group.


RESULTS
The ABR thresholds were significantly elevated in animals from all groups after cisplatin treatment. A maximum accumulation of Pt for inner ear and brain was revealed around the first week: 3.175 (57%) and 0.342 (72%), respectively. Pt significantly accumulated in greater quantities in ear than in brain (p<0.01) and was cleared at a higher rate in brain than in ear (p<0.01) following cochlea/brain ratio analysis. No statistically significant correlation was found between amounts of Pt and hearing loss in the study animals.
Ramírez-Camacho
R
R
Ear Research Group, Department of Otorhinolaryngology, Hospital Universitario Puerta de Hierro, Universidad Autónoma de Madrid, Madrid, Spain. rramirezc@seorl.net
Fernández
D Esteban
DE
Verdaguer
J M
JM
Gómez
M M Gómez
MM
Trinidad
A
A
García-Berrocal
J R
JR
Corvillo
M A Palacios
MA
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000633:toxicity*; D001921:Brain / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000502:physiology; D002945:Cisplatin / Q000493:pharmacokinetics* / Q000633:toxicity*; D003638:Deafness / Q000097:blood / Q000139:chemically induced*; D007758:Ear, Inner / Q000378:metabolism; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D007274:Injections, Intraperitoneal; D007424:Intracellular Fluid / Q000378:metabolism; D008657:Metabolic Clearance Rate / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
D000970:Antineoplastic Agents; D002945:Cisplatin