Dose-dependent effect of 8-day cisplatin administration upon the morphology of the albino guinea pig cochlea

Numerous studies investigating cisplatin ototoxicity in animals have been p erformed, but it is difficult to derive a clear dose-effect relation from t hese studies. The degree of cisplatin-induced ototoxicity depends on a mult itude of,factors. Many parameters, such as dose, mode of administration, do sage schedule and concomitant administration of protective additives, vary among the published studies. Therefore, we performed a basic dose-effect st udy on cisplatin ototoxicity in the guinea pig. Albino guinea pigs were tre ated with cisplatin at daily doses of either 0.7, 1.0, 1.25, 1.5 or 2.0 mg/ kg for 8 consecutive days. Electrocochleography was performed on day 10 aft er which the cochleas were removed and processed for histological examinati on. The electrophysiological results showed a marked transition from almost no ototoxic effect to a large effect between a daily dose of 1.25 and 1.5 mg/kg (Stengs et al., 1998). Outer hair cell (OHC) counts corresponded well with the electrophysiological results. At daily doses of 0.7, 1.0 and 1.25 mg/kg no statistically significant OHC loss was observed, whereas OHC loss averaged 60% and 65% in the basal turns at daily doses of 1.5 and 2.0 mg/k g, respectively. Morphological changes in the stria vascularis were present only in cochleas from animals treated with cisplatin doses of 1.0, 1.25 an d 1.5 mg/kg/day. Cochleas from animals treated with a daily cisplatin dose of 2.0 mg/kg for 8 consecutive days showed an endolymphatic hydrops. The pr esent study shows that cisplatin, administered at a daily dose of 1.5 mg/ k g for 8 consecutive days, provides a degree of OHC loss that is well suited to study the effects of putative protective agents and possible hair cell recovery. (C) 2000 Elsevier Science B.V. All rights reserved.