Targeted Amelioration of Cisplatin‐Induced Ototoxicity in Guinea Pigs. (30th July 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: 2014-07-30
• 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

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.