Targeted Amelioration of Cisplatin-Induced Ototoxicity in Guinea Pigs. (November 2014)

• Record Type: Journal Article
• Authors: Mohan, Shaulnie; Smyth, Brendan J.; Namin, Arya; Phillips, Grady; Gratton, Michael Anne
• Is Part Of: Otolaryngology--head and neck surgery. Volume 151:Number 5(2014:Nov.)
• Page Start: 836
• Page End: 839
• Publication Date: 2014-11
• Subjects: otoprotection -- drug delivery -- ABR -- L-N-acetylcysteine -- nanocapsules -- trans-tympanic -- systemic -- glutathione -- ROS; Head -- Surgery -- Periodicals; Neck -- Surgery -- Periodicals; Otolaryngology -- Periodicals; 617.51
• DOI: 10.1177/0194599814544877
• Languages: English
• ISSNs: 0194-5998

Abstract

This pilot study compared otoprotection provided by trans-tympanic formulations and systemic intraperitoneal administration of L-N-acetylcysteine from cisplatin-induced cochlear oxidative stress. Protection was assessed by measures of hearing loss and cochlear glutathione levels. All groups received an equivalent single dose of L-N-acetylcysteine followed by cisplatin. Cisplatin was administered subcutaneously for 3 days (5.5 mg/kg/day). Two hours prior to day 1 cisplatin, L-N-acetylcysteine was administered either intraperitoneally (250 mg/kg), trans-tympanic as 2% L-N-acetylcysteine in gel, or trans-tympanic as L-N-acetylcysteine–loaded nanocapsules in gel. Hearing was assessed prior to and 3 days after cisplatin followed by microdissection of cochlear tissue. The levels of reduced (GSH) and oxidized (GSSG) glutathione in homogenized tissue supernatants were determined via luminometry. Intraperitoneal L-N-acetylcysteine administration preceding cisplatin resulted in less hearing loss and a higher GSH/GSSG ratio than either trans-tympanic formulation. This suggests that for equivalent doses of L-N-acetylcysteine, systemic rather than targeted cochlear delivery provides increased otoprotection from cisplatin ototoxicity.