Abstract

OBJECTIVE: Valproic acid (VPA) is a widely used anti-convulsant. There have been some reports that VPA causes hearing loss and tinnitus, and oxidative stress has been associated with VPA toxicity. Thus, we were interested in the effects of VPA on noise-induced hearing loss.

MATERIALS and METHODS: Animals were divided into two groups, as follows: treatment with VPA (30 mg/kg daily) and treatment with phosphate buffered saline (PBS) (control group). VPA and PBS were injected intraperitoneally once daily for 20 days (3 days before noise exposure until 2 weeks after noise exposure). Acoustic trauma was induced by continuous white noise at 110 dB SPL for 4 h/day for 3 days. After noise trauma, hearing results, anti-oxidant enzyme analysis, and histological findings were compared in both groups.

RESULTS: An auditory brainstem response threshold shift was observed in both groups 1 day after noise exposure. Two weeks following noise exposure, there was gradual recovery to normal levels in the control group; however, in the VPA group, especially with respect to 4 kHz sound, hearing loss recovered less than in the control group (p<0.05). Also, based on morphologic studies, more outer hair cell loss was observed (especially 10-12 mm from the apex in the 4 kHz area) in the VPA group than in the control group (p<0.05). Anti-oxidative enzyme mRNA expression was significantly increased in the VPA group compared to the control group (p<0.05).

CONCLUSION: This study demonstrates that VPA may have a harmful effect on noise-induced ototoxicity via oxidative stress in guinea pigs.