title: A sensitive animal model to assess acute and chronic ototoxic effects.
abstract: BACKGROUND
  Ototoxic side effects of aminoglycosides or cisplatin are strongly influenced by the nutritional state of the experimental animal. We previously demonstrated that guinea pigs fed a low-protein diet are a sensitive model to investigate chronic ototoxic effects of drugs. We now demonstrate that this model is equally sensitive to acute ototoxic insults.
  
  
  METHODS
  Guinea pigs were fed either a full-protein (18.5% protein) or a low-protein (7% protein) diet. Gentamicin sulfate was given as a single injection (100 mg/kg of body weight subcutaneously), followed 90 minutes later by varying concentrations of ethacrynic acid intravenously. Auditory function was assessed by auditory brain-stem response and morphologic characteristics in surface preparations of the organ of Corti.
  
  
  RESULTS
  In animals fed a full-protein diet, 35 mg of ethacrynic acid per kilogram of body weight was required for a significant threshold shift at all frequencies tested (3, 8, and 18 kHz). In animals fed a low-protein diet, 15 mg of ethacrynic acid per kilogram significantly elevated threshold at all frequencies, and 20 mg/kg caused a profound threshold shift (> 90 dB). Hair cell loss in the organ of Corti paralleled the pathophysiological findings.
  
  
  CONCLUSIONS
  A metabolically challenged animal may better represent the situation of a severely ill patient undergoing drug therapy. Therefore, studies in diet-restricted animals may be more appropriated than studies in healthy animals for an assessment of potential adverse therapeutic side effects.
authors.affiliation: Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan, Ann Arbor, USA.
authors.forename: J
authors.initials: J
authors.lastname: Lautermann
authors.forename: J
authors.initials: J
authors.lastname: Schacht
mesh_terms: D000208:Acute Disease; D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity; D001309:Auditory Threshold; D018753:Diet, Protein-Restricted; D004195:Disease Models, Animal; D004232:Diuretics / Q000633:toxicity; D004976:Ethacrynic Acid / Q000633:toxicity; D016057:Evoked Potentials, Auditory, Brain Stem; D005839:Gentamicins / Q000633:toxicity; D006168:Guinea Pigs; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009925:Organ of Corti / Q000473:pathology
chemical_list: D000900:Anti-Bacterial Agents; D004232:Diuretics; D005839:Gentamicins; D004976:Ethacrynic Acid