Protective effect of systemic administration of pravastatin against noise-induced hearing loss in the Fischer 344/NHsd rat substrain
Creators:Sanders, Jennifer Morgan
Advisor:Bielefeld, Eric C.
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Publisher:Ohio State University. Department of Speech and Hearing Science
Series/Report no.:Ohio State University. Department of Speech and Hearing Science. Doctor of Audiology Capstone Projects. 2012
The deleterious effects of noise-induced hearing loss (NIHL) on the auditory system have been well documented, contributing to temporary thresholds shifts (TTS) and permanent threshold shifts (PTS). The generation of reactive oxygen species (ROS) greatly contributes to the pathogenesis of NIHL, and as such is a target for pharmacological intervention by strengthening the antioxidant defense system in the body. Previous studies suggest that pravastatin may lower ROS production and block apoptotic cell death. As such, the aim of this study was to examine the protective effect of pravastatin against noise in the Fischer 344/NHsd rat substrain. The noise condition was a 2-octave band continuous noise of 4 kHz – 16 kHz, delivered at 110 dB SPL combined with 120 dB pSPL impacts. In the treated group, pravastatin was administered via intraperitoneal injections (12 mg/kg) 24 hours before noise exposure; 1 hour prior to and 1 hour following noise exposure; and then 24 hours post noise exposure. Threshold shifts for the treated versus untreated groups were assessed at 6 frequencies (5, 10, 15, 20, 30, and 40 kHz) and were obtained 1 day and 14 days after the noise to document TTS and 28 days post noise to document PTS. The 3-way ANOVA did not show a significant main effect (p < .05) of Group or Frequency, nor any significant interaction involving treatment groups. There was a trend toward significance for the interaction of Day and Group (p = 0.057). Recovery functions indicated that, from Day 14 to Day 28, the treated group demonstrated a decrease in thresholds that the untreated control group did not. While this study did not indicate a significant protective effect of pravastatin, further investigation of pravastatin’s protective capacity against NIHL is needed to extrapolate therapeutic strategies caused by ROS overproduction.
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