title: The effect of radiotherapy on gentamicin ototoxicity: an animal model.
abstract: OBJECTIVE
  Patients undergoing radiotherapy (RT) often present with serious bacterial infections requiring the use of antibiotic treatment. Gentamicin is a commonly used aminoglycoside antibiotic, whose ototoxicity remains a major problem in clinical use. The objective of this study was to determine whether radiation exposure can influence gentamicin-induced ototoxicity.
  
  
  METHODS
  Prospective animal study.
  
  
  METHODS
  Animal care facilities of the Montreal Children's Hospital Research Institute.
  
  
  METHODS
  Sixteen guinea pigs received low-dose RT unilaterally for 4 weeks (total: 48 Gy). Animals then received low or high doses of gentamicin (40 mg/kg/d and 80 mg/kg/d) for 10 days. The ears were divided into 4 groups: gentamicin 40 mg, gentamicin 80 mg, gentamicin 40 mg + RT, and gentamicin 80 + RT. Auditory brainstem responses and distortion products otoacoustic emissions were assessed at baseline and before and after gentamicin treatment. Cochlear morphology using light and scanning electron microscopy were evaluated.
  
  
  RESULTS
  High-dose gentamicin caused significant auditory brainstem response threshold shifts (P = .020), with greater hearing loss in the irradiated ear (difference of 23.6 + 7.5 dB). All animals exposed to high-dose gentamicin had head tilts toward the radiated side. Cochlear morphology revealed the greatest hair cell damage in the gentamicin 80 + RT group followed by gentamicin 80.
  
  
  CONCLUSIONS
  Results suggest that radiation can exacerbate the ototoxicity of gentamicin at high doses.
authors.affiliation: McGill Auditory Sciences Laboratory, McGill University, Montreal, Quebec, Canada Department of Otolaryngology-Head and Neck Surgery, The Montreal Children's Hospital, Montreal, Quebec, Canada.
authors.forename: Aren
authors.initials: A
authors.lastname: Bezdjian
authors.affiliation: McGill Auditory Sciences Laboratory, McGill University, Montreal, Quebec, Canada Department of Otolaryngology-Head and Neck Surgery, The Montreal Children's Hospital, Montreal, Quebec, Canada.
authors.forename: Mario A
authors.initials: MA
authors.lastname: Mujica-Mota
authors.affiliation: Medical Physics Unit, McGill University, Montréal, Quebec, Canada Department of Radiation Oncology, Jewish General Hospital, Montreal, Quebec, Canada.
authors.forename: Slobodan
authors.initials: S
authors.lastname: Devic
authors.affiliation: McGill Auditory Sciences Laboratory, McGill University, Montreal, Quebec, Canada Department of Otolaryngology-Head and Neck Surgery, The Montreal Children's Hospital, Montreal, Quebec, Canada sam.daniel@mcgill.ca.
authors.forename: Sam J
authors.initials: SJ
authors.lastname: Daniel
mesh_terms: D000818:Animals; D001707:Biopsy, Needle; D003051:Cochlea / Q000187:drug effects* / Q000528:radiation effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004334:Drug Administration Schedule; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects / Q000528:radiation effects; D005260:Female; D005839:Gentamicins / Q000494:pharmacology / Q000633:toxicity*; D006168:Guinea Pigs; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced* / Q000473:pathology; D007150:Immunohistochemistry; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects / Q000528:radiation effects; D011829:Radiation Dosage; D011897:Random Allocation; D012016:Reference Values; D012680:Sensitivity and Specificity
chemical_list: D005839:Gentamicins
keywords: aminoglycoside; gentamicin; guinea pig; hearing loss; radiation; radiotherapy