Perilymphatic application of alpha-melanocyte stimulating hormone ameliorates hearing loss caused by systemic administration of cisplatin.
It has previously been demonstrated that ototoxicity induced by systemic administration of cisplatin is reduced by concomitant systemic administration of alpha-melanocyte stimulating hormone (alpha-MSH). In this study we investigated the effects of cochlear, perilymphatic application of alpha-MSH during intraperitoneal administration of cisplatin. Guinea pigs, implanted with a round-window electrode, allowing daily monitoring of the compound action potential (CAP), and also implanted with a mini-osmotic pump, pumping at a rate of 0.25 microl/h either physiological saline or alpha-MSH solution (0.02, 2, and 20 microg/ml), were treated daily with a bolus injection of cisplatin (2 mg/kg) until the electrocochleogram showed a persistent decrease in CAP amplitude (> or = 40 dB threshold shift at 8 kHz). Then, cisplatin treatment was stopped, but intracochlear perfusion of alpha-MSH or physiological saline was continued for 10 days to evaluate possible effects of alpha-MSH on the expected recovery. On day 10, the animals were killed and the cochleas were fixed and processed for histological analysis. All groups required 6-7 days of cisplatin to reach the criterion CAP threshold shift. Ten days after cessation of the cisplatin treatment, recovery of the CAP was observed in all groups and at all frequencies, although it was more pronounced at the lower frequencies. With respect to recovery, small statistically significant differences were found between the saline and the alpha-MSH co-treated groups. Histological results showed significantly less outer hair cell (OHC) loss in the group co-treated with 2 microg/ml alpha-MSH as compared to the group co-treated with saline. Since alpha-MSH was directly delivered to the cochlea, the ameliorating effect of alpha-MSH on OHC survival is likely to involve a cochlear target.
Hearing Research Laboratories, Department of Otorhinolaryngology, University Medical Center Utrecht, NL-3508 GA Utrecht, The Netherlands.
Francisca L C
FL
Wolters
Sjaak F L
SF
Klis
Frank P T
FP
Hamers
John C M J
JC
de Groot
Guido F
GF
Smoorenburg
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001300:Audiometry, Evoked Response; D016923:Cell Death; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects*; D003052:Cochlear Aqueduct / Q000503:physiopathology*; D003055:Cochlear Microphonic Potentials / Q000187:drug effects; D004056:Differential Threshold; D004357:Drug Synergism; D005260:Female; D006168:Guinea Pigs; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D034381:Hearing Loss / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology*; D007260:Infusion Pumps; D007274:Injections, Intraperitoneal; D020127:Recovery of Function; D000521:alpha-MSH / Q000008:administration & dosage*
D000970:Antineoplastic Agents; D000521:alpha-MSH; D002945:Cisplatin