The electroreceptor organ of the catfish, Ictalurus melas, as a model for cisplatin-induced ototoxicity

• Published in: Neuroscience Vol. 91; no. 2; pp. 745 - 751
• Main Authors: Peters, R.C, Mommersteeg, P.M.C, Heijmen, P.S
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-01-1999; Elsevier
• Subjects: Afferent Pathways - drug effects; Afferent Pathways - physiology; Analysis of Variance; Animals; Antineoplastic Agents - toxicity; Biological and medical sciences; CDDP; cisplatin; Cisplatin - toxicity; Drug toxicity and drugs side effects treatment; Electric Organ - drug effects; Electric Organ - physiology; electroreception; Female; Freshwater; hair cell; Hair Cells, Auditory, Inner - drug effects; Ictaluridae; Ictalurus melas; Male; Mammals; Medical sciences; ototoxicity; Pharmacology. Drug treatments; Skin - innervation; Time Factors; Toxicity: respiratory system, ent, stomatology; electroreception; CDDP; cisplatin; ototoxicity; OHC, outer hair cell; hair cell; Antineoplastic agent; Electroreceptor; Vertebrata; Toxicity; Animal; Pisces; Electrophysiology; Ciliated cell; Cisplatin
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(98)00658-7

The ototoxic side-effects of the anti-cancer drug cisplatin (
cis-diaminedichloroplatinum) have been widely investigated. However, the exact site of action remains unclear. In this study, the electroreceptor organ of the freshwater catfish
Ictalurus melas is used as a model for examining the acute effects of cisplatin. The sensory cells in the electroreceptor organ are homologous to the inner hair cells in the cochlea of mammals. The effects of cisplatin administration can be investigated by
in vivo recording of the spike trains from the electroreceptor organ primary afferents. Exposure of electroreceptor organs to 330
μM cisplatin for 1
h causes the spontaneous activity to drop, the overall sensitivity to diminish and the shape of the frequency characteristics to change. These effects persist in the week after administration. Control levels have returned at day 22.
These results demonstrate an acute and, with considerable hysteresis, reversible cisplatin effect on the electroreceptor organs, which is to a large extent consistent with the cisplatin-induced effects in isolated hair cells in mammals. The time-course of the effect supports the hypotheses that ion channels are blocked immediately by cisplatin administration, and that cisplatin metabolites disturb enzymatic cellular processes.