Effects of superoxide dismutase and U74389G on acute trimethyltin-induced cochlear dysfunction.
Reactive oxygen species (ROS) generation has been implicated in the ototoxicity induced by several pharmaceutical agents. The present study examined the efficacy of the ROS scavenger polyethylene glycol-conjugated superoxide dismutase (PEG.SOD), and a 21-aminosteroid (U74389G), in ameliorating the acute cochlear dysfunction induced by the environmental ototoxicant trimethyltin chloride (TMT). Thirty pigmented guinea pigs were divided into six experimental conditions, as defined by preexposure and exposure administrations: saline-saline, PEG.SOD-saline, U74389G-saline, saline-TMT, and U74389G-TMT. Electrophysiological potentials (compound action potential (CAP) and cochlear microphonic (CM) were recorded for 10 acoustic frequencies, and then a preexposure agent (U74389G, 4.5mg/kg; PEG.SOD, 10,000 U/kg; or 0.9% saline) was administered i.v. Thirty minutes later, potentials were retested, and an exposure agent (0.9% saline or TMT, 0.5 mg/kg) was administered i.p. CM and CAP were retested at 30, 60, and 90 min postexposure time points, in order to assess changes in auditory responsiveness. Mean changes in 1.0-microV root mean square CM isopotential values did not differ significantly in any group from those of saline-saline controls. In the saline-TMT group, CAP thresholds increased significantly at all test frequencies relative to those of the saline-saline control group. While mean CAP threshold shifts in the U74389G-TMT group were as great as those in the saline-TMT group, such values in the PEG.SOD-TMT group were significantly lower. These results suggest that ROS formation may be involved in acute TMT-induced CAP disruption, for which PEG.SOD, but not U74389G, provides partial protection.
Clerici
W J
WJ
Department of Surgery, Chandler Medical Center, University of Kentucky College of Medicine, Lexington 40536-0084, USA.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D003051:Cochlea / Q000187:drug effects* / Q000502:physiology; D003055:Cochlear Microphonic Potentials / Q000187:drug effects; D005072:Evoked Potentials, Auditory / Q000187:drug effects; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006168:Guinea Pigs; D008297:Male; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011281:Pregnatrienes / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000633:toxicity; D013482:Superoxide Dismutase / Q000494:pharmacology*; D014298:Trimethyltin Compounds / Q000633:toxicity*
D000975:Antioxidants; D016166:Free Radical Scavengers; D011281:Pregnatrienes; D017382:Reactive Oxygen Species; D014298:Trimethyltin Compounds; C074965:U 74389F; C046488:trimethyltin; D011092:Polyethylene Glycols; D013482:Superoxide Dismutase; C063471:polyethylene glycol-superoxide dismutase