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It has previously been demonstrated that ototoxicity induced by systemic administration of cisplatin is reduced by concomitant administration of melanocortins, like α-melanocyte stimulating hormone (α-MSH). However, these experiments were hampered by large interanimal variability. Therefore, we re-investigated the effects of systemically administered α-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 μl/h physiological saline or cisplatin solution (15 μg/ml), were co-treated daily with a subcutaneous bolus injection of either α-MSH (75 μg/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 α-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/α-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 α-MSH delays cisplatin ototoxicity. Since cisplatin was delivered directly to the cochlea, the ameliorating effect of α-MSH probably involves a cochlear target. [Copyright &y& Elsevier]

The effect of noise exposure on the auditory system is well known from animal studies. However, most of the studies concern short-term exposure conditions. The purpose of the present research was to find the dose-effect curve for hearing loss in rats following 5 days of noise exposure. Three groups of eight Wag/Rij rats were exposed to broad band noise at levels of 90, 100 and 110 dB SPL for 8 hours/day and 5 consecutive days. An additional group of eight rats served as the control group. Between three and seven weeks after the exposure, hearing was tested by electrocochleography (CAP) and distortion product otoacoustic emissions (DPOAE). Subsequently, the cochleas were morphologically examined. Only the highest two exposure levels affected hearing. The DPOAE growth curves at 4, 8 and 16 kHz and the CAP growth curves at 4, 8, 12, 16 and 24 kHz were affected after the 110 dB SPL broad band noise. After the 100 dB SPL noise, only the 12 kHz CAP growth curve was affected. At the light-microscopic level, OHC damage was not detected in this study.