title: Dose-dependent effect of 8-day cisplatin administration upon the morphology of the albino guinea pig cochlea.
abstract: Numerous studies investigating cisplatin ototoxicity in animals have been performed, but it is difficult to derive a clear dose-effect relation from these studies. The degree of cisplatin-induced ototoxicity depends on a multitude of factors. Many parameters, such as dose, mode of administration, dosage schedule and concomitant administration of protective additives, vary among the published studies. Therefore, we performed a basic dose-effect study on cisplatin ototoxicity in the guinea pig. Albino guinea pigs were treated 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 after which the cochleas were removed and processed for histological examination. 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/kg, respectively. Morphological changes in the stria vascularis were present only in cochleas from animals treated with cisplatin doses of 1.0, 1.25 and 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 present study shows that cisplatin, administered at a daily dose of 1.5 mg/kg 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.
authors.affiliation: Hearing Research Laboratories, Department of Otorhinolaryngology, University Medical Center, Room G.02.531, P.O. Box 85.500, 3508 GA, Utrecht, The Netherlands.
authors.forename: R M
authors.initials: RM
authors.lastname: Cardinaal
authors.forename: J C
authors.initials: JC
authors.lastname: de Groot
authors.forename: E H
authors.initials: EH
authors.lastname: Huizing
authors.forename: J E
authors.initials: JE
authors.lastname: Veldman
authors.forename: G F
authors.initials: GF
authors.lastname: Smoorenburg
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000506:poisoning*; D001306:Auditory Pathways / Q000187:drug effects / Q000473:pathology; D002452:Cell Count / Q000187:drug effects; D002945:Cisplatin / Q000506:poisoning*; D003051:Cochlea / Q000187:drug effects* / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D018159:Endolymphatic Hydrops / Q000139:chemically induced / Q000473:pathology; D005260:Female; D006168:Guinea Pigs; D018072:Hair Cells, Auditory, Outer / Q000473:pathology; D009475:Neurons, Afferent / Q000473:pathology; D009925:Organ of Corti / Q000187:drug effects / Q000473:pathology; D013136:Spiral Ganglion / Q000187:drug effects / Q000473:pathology; D013316:Stria Vascularis / Q000187:drug effects / Q000473:pathology; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin