Systemic co-treatment with alpha-melanocyte stimulating hormone delays hearing loss caused by local cisplatin administration in guinea pigs.
It has previously been demonstrated that ototoxicity induced by systemic administration of cisplatin is reduced by concomitant administration of melanocortins, like alpha-melanocyte stimulating hormone (alpha-MSH). However, these experiments were hampered by large interanimal variability. Therefore, we re-investigated the effects of systemically administered alpha-MSH during local (intracochlear) administration of cisplatin. Guinea pigs, implanted with a round-window electrode, allowing daily monitoring of the compound action potentials (CAPs), and a mini-osmotic pump, pumping either 0.5 microl/h physiological saline or cisplatin solution (15 microg/ml), were co-treated daily with a subcutaneous bolus injection of either alpha-MSH (75 microg/kg) or physiological saline for 1 week or until the electrocochleogram showed a persistent decrease in CAP amplitude (40 dB threshold shift at 8 kHz). Next, the animals were sacrificed and the cochleas were processed for histology. After 2-3 days, cisplatin alone caused a threshold shift at all frequencies (2-16 kHz). Co-administration with alpha-MSH consistently delayed the criterion threshold shift by 1 day. When the 40 dB criterion had been reached, similar outer hair cell losses in both the cisplatin/alpha-MSH- and cisplatin/saline-treated groups were observed. This experiment confirms that direct administration of cisplatin into the cochlea results in considerably less interanimal variability than systemic administration and that co-treatment with alpha-MSH delays cisplatin ototoxicity. Since cisplatin was delivered directly to the cochlea, the ameliorating effect of alpha-MSH probably involves a cochlear target.
Hearing Research Laboratories, University Medical Center Utrecht, Room G02.531, P.O. Box 85 500, 3508 GA Utrecht, The Netherlands. f.l.c.wolters@kmb.azu.nl
Francisca L C
FL
Wolters
Sjaak F L
SF
Klis
John C M J
JC
de Groot
Frank P T
FP
Hamers
Diane M
DM
Prieskorn
Josef M
JM
Miller
Guido F
GF
Smoorenburg
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000037:antagonists & inhibitors / Q000633:toxicity*; D001309:Auditory Threshold / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage* / Q000037:antagonists & inhibitors / Q000633:toxicity*; D003051:Cochlea / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D003055:Cochlear Microphonic Potentials / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects / Q000473:pathology; D034381:Hearing Loss / Q000139:chemically induced* / Q000517:prevention & control*; D000521:alpha-MSH / Q000008:administration & dosage*
D000970:Antineoplastic Agents; D000521:alpha-MSH; D002945:Cisplatin