title: Targeted amelioration of cisplatin-induced ototoxicity in guinea pigs.
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.
authors: Department of Otolaryngology-Head & Neck Surgery, Saint Louis University, Saint Louis, Missouri, USA smohan3@slu.edu.
authors: Shaulnie
authors: S
authors: Mohan
authors: Baxter Health Care Corporation, Deerfield, Illinois, USA.
authors: Brendan J
authors: BJ
authors: Smyth
authors: Department of Otolaryngology-Head & Neck Surgery, Saint Louis University, Saint Louis, Missouri, USA.
authors: Arya
authors: A
authors: Namin
authors: Department of Otolaryngology-Head & Neck Surgery, Saint Louis University, Saint Louis, Missouri, USA.
authors: Grady
authors: G
authors: Phillips
authors: Department of Otolaryngology-Head & Neck Surgery, Saint Louis University, Saint Louis, Missouri, USA.
authors: Michael Anne
authors: MA
authors: Gratton
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage*; D000818:Animals; D002945:Cisplatin / Q000009:adverse effects*; D005260:Female; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D006168:Guinea Pigs; D034381:Hearing Loss / Q000139:chemically induced* / Q000188:drug therapy*; D018384:Oxidative Stress; D010865:Pilot Projects; D014432:Tympanic Membrane
chemical_list: D016166:Free Radical Scavengers; D002945:Cisplatin; D000111:Acetylcysteine
keywords: ABR; L-N-acetylcysteine; ROS; drug delivery; glutathione; nanocapsules; otoprotection; systemic; trans-tympanic