The Effect of Radiotherapy on Gentamicin Ototoxicity: An Animal Model. (June 2015)

• Record Type: Journal Article
• Authors: Bezdjian, Aren; Mujica-Mota, Mario A.; Devic, Slobodan; Daniel, Sam J.
• Is Part Of: Otolaryngology--head and neck surgery. Volume 152:Number 6(2015:Jun.)
• Page Start: 1094
• Page End: 1101
• Publication Date: 2015-06
• Subjects: radiotherapy -- radiation -- gentamicin -- aminoglycoside -- guinea pig -- hearing loss; Head -- Surgery -- Periodicals; Neck -- Surgery -- Periodicals; Otolaryngology -- Periodicals; 617.51
• DOI: 10.1177/0194599815573197
• Languages: English
• ISSNs: 0194-5998

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. Study Design: Prospective animal study. Setting: 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. Conclusion: Results suggest that radiation can exacerbate the ototoxicity of gentamicin at high doses.