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This study's purpose was to determine if a correlation exists between cochlear antioxidant activity changes and auditory function after induction of aminoglycoside (AG) ototoxicity. Two groups of five 250-350 g albino guinea pigs served as subjects. For 28 days, albino guinea pigs were administered either 200 rog/kg/day amikacin, or saline subcutaneously. Auditory brainstem response testing was performed prior to the first injection and again before sacrifice, 28 days later. Cochleae were harvested and superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase activities and malondialdehyde levels were measured. All antioxidant enzymes had significantly lower activity in the amikacin group (p < 0.05) than in the control group. The difference in cochlear antioxidant enzyme activity between groups inversely correlated significantly with the change in ABR thresholds. The greatest correlation was for the high frequencies, which are most affected by aminoglycosides. This study demonstrates that antioxidant enzyme activity and amikacin-induced hearing loss significantly covary. [ABSTRACT FROM AUTHOR]

This study describes audiologic methodology and results for evaluating potential ototoxicity in a phase I clinical trial of a new glycopeptide. This study was conducted under good clinical practices, which are regulated by the US Food and Drug Administration (FDA) (21 Code of Federal Regulations), and input from the FDA was sought prior to study implementation. Healthy, normal volunteers underwent extensive medical and audiologic assessments as part of this phase I dose- escalation study of dalbavancin, a new glycopeptide, to assess potential side effects. Audiologic monitoring included air-conduction thresholds in the conventional (0.25-8 kHz) and high-frequency (10-16 kHz) ranges. At baseline, subjects were also tested using word recognition, bone conduction testing if indicated, and tympanometry. Full testing was to be repeated if any subject met the American Speech-Language-Hearing Association (ASHA) 1994 criteria for ototoxic change. However, no subjects demonstrated ototoxic change after receiving dalbavancin, nor were any false-positive results obtained. [ABSTRACT FROM AUTHOR]

D-methionine (D-met) protects against cisplatin (CDDP) ototoxicity, but the mechanisms are not well understood. This study investigated D-met protection of cochlear oxidative state as measured by superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR), and malondiadehyde (MDA) levels. The design comprised four groups of five rats each: (1) a saline control group, (2) a CDDP-only-treated group, (3) a CDDP group pretreated with D-met, and (4) a group receiving only D-met. Auditory brainstem response testing (ABR) was performed before and 3 days after injection. CDDP alone caused marked hearing loss; significantly reduced SOD, CAT, and GR levels; and increased MDA levels, but D-met pretreatment protected against these changes. These studies suggest that D-met protects cochlear antioxidant enzyme levels from CDDP-induced decrements. The excellent correlation of enzyme levels with hearing loss and weight loss suggests that antioxidant enzyme level protection may underlie, at least in part, D-met's otoprotective action. [ABSTRACT FROM AUTHOR]

Glutathione (GSH) provides an important antioxidant and detoxification pathway. We tested to determine if direct administration of GSH or GSH ester could reduce cisplatin- (CDDP) induced ototoxicity. We tested eight groups of five rats each: a control group, a group receiving 16 mg/kg ip CDDP infused over 30 minutes, and six groups receiving either GSH or GSH ester at 500, 1000, or 1500 mg/kg intraperitoneally 30 minutes prior to 16 mg/kg CDDP. Auditory brainstem response thresholds were measured for click and tone-burst stimuli at baseline and 3 days later. Outer hair cell (OHC) loss was measured for the apical, middle and basal turns. The 500 mg/kg GSH ester reduced hearing loss and OHC loss, but protection decreased as dosage increased, suggesting possible toxicity. GSH was not significantly protective. The best GSH ester protection was less than we have previously reported with D-methionine. [ABSTRACT FROM AUTHOR]