Ototoxicity of carboplatin in guinea pigs.
Since carboplatin (CBDCA) is a platinum compound of second generation, its ototoxicity was investigated. In order to assess the ototoxicity, hearing acuity was measured based on the compound action potential (AP), and the organ of Corti was morphologically studied using scanning electron microscopy (SEM) and succinate dehydrogenase (SDH) staining in guinea pigs treated with CBDCA. CBDCA induced morphological changes in the organ of Corti when the guinea pigs received 50 mg/kg daily for 2 or 3 days. The threshold value of AP was elevated 10 to 25 dB in treated animals, as compared with the control value. The SEM study and SDH staining revealed that the administration caused scattered degeneration of the outer hair cells (OHCs), and the inner hair cells remained intact. These lesions were milder than those of OHCs treated with cisplatin (CDDP). The rapid elimination of CBDCA from the kidney and the inner ear seems to account for the low ototoxicity of this compound. Although CBDCA is less toxic than CDDP, it may affect hearing function if patients suffer from renal dysfunction or if the organ of Corti is vulnerable.
Saito
T
T
Department of Otorhinolaryngology, Fukui Medical School, Japan.
Saito
H
H
Saito
K
K
Wakui
S
S
Manabe
Y
Y
Tsuda
G
G
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000970:Antineoplastic Agents; D016190:Carboplatin; D002470:Cell Survival / Q000187:drug effects; D004056:Differential Threshold; D004423:Ear / Q000187:drug effects* / Q000502:physiology; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D008855:Microscopy, Electron, Scanning; D009410:Nerve Degeneration; D009944:Organoplatinum Compounds / Q000506:poisoning*; D013194:Staining and Labeling; D013385:Succinate Dehydrogenase / Q000378:metabolism
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D016190:Carboplatin; D013385:Succinate Dehydrogenase