The effect of caffeine on hearing in a guinea pig model of acoustic trauma.

OBJECTIVE: Caffeine is a widely consumed substance affecting the metabolism of adenosine and cellular metabolism of calcium. Noise also affects these metabolic pathways while inducing hearing loss. The aim of this study was to determine the effect of daily intake of caffeine on hearing loss after an episode of acoustic trauma in guinea pigs. MATERIALS AND METHODS: In this pilot study, forty guinea pigs were randomly divided into four groups: group I (control, n=10) received intraperitoneal saline, group II (n=10) received intraperitoneal caffeine (120 mg/kg/day) for 14 days, group III (n=10) was exposed to noise (tone of 6 kHz at 120 dB for one hour) and group IV (n=10) was exposed to noise as group III and received caffeine as group II. Auditory brainstem responses were measured at four different frequencies (8, 16, 20, and 25 kHz) prior to and at intervals of 1h, 3 days, 10 days, and 14 days after the initial treatment. On day 14, morphological analysis was performed to assess the effects of caffeine on acoustic trauma. RESULTS: Aggravated hearing loss was observed in group IV after 10 days of follow-up. After 14 days, one of the four frequencies (8 kHz) tested showed statistically significant greater impairment in hearing (8.2 ± 3.6 dB, p=0.026). Auditory hair cells showed no difference while spiral ganglion cell counts were diminished in group IV (p<0.05). CONCLUSION: These findings indicate that caffeine may have a detrimental effect on hearing recovery after a single event of acoustic trauma.

Hearing loss in type 1 diabetes: Are we facing another microvascular disease? A meta-analysis.

OBJECTIVE: Evidence shows type 1 diabetes(T1D) leads to vascular damage and neuropathy. The purpose of this study was to perform a systematic review and a meta-analysis to assess the evidence of the effects of T1D on hearing function. METHODS: Three electronic databases were used. The articles were independently reviewed by two authors using predefined inclusion criteria to identify eligible studies. They were then classified as high or low methodological quality. Meta-analysis was performed on pooled data of hearing loss(HL) prevalence, pure tone audiometry(PTA), otoacoustic emissions(OAE) and auditory brainstem response(ABR). RESULTS: Twenty-one articles fulfilled the inclusion criteria. In all studies, HL was defined as pure tone greater than 20 dB in at least one frequency. The prevalence of HL ranged between 5.17% and 48% for diabetics, which was higher than in controls which ranged between 0% à 40% (OR = 7.7, 95% CI 3.32-17.98, p < 0.05 and I2 = 40%). The tendency of mean thresholds of PTA was higher in diabetics than in controls, with results being statistically significant at 250, 500 and 1000 Hz. OAE were significantly lower in diabetic patients. ABR latencies were longer in T1D group compared to controls and were statistical significant. CONCLUSIONS: Patients with T1D have a significantly greater prevalence of HL compared to the control group. These damages could be compared to other microvascular diseases. Further studies are needed to assess whether hearing testing should be considered as a part of the screening process in T1D patients and therefore, secondary preventive treatment may be warranted as well.

Eye color as a risk factor for acquired sensorineural hearing loss: a review.

Eye color may be an indicator of inner ear melanin content and has been associated with hearing loss. There is controversy as to whether eye color has an effect on acquired causes of sensorineural hearing loss. This review was conducted to analyze the literature evaluating the relationship between eye color and causes of sensorineural hearing loss. Six databases were searched to identify eligible studies. Included articles were independently assessed for quality by two authors. Eighteen articles were eligible for review. Eye color was not found to have an effect in the non-exposed population or in presbycusis. In noise-induced sensorineural hearing loss, light-eyed patients had more significant loss following noise exposure, although the variability reported due to eye color was modest (r(2) = 0.01-0.14). Two out of three studies reported that dark eye color is associated with cisplatin ototoxicity. In one study, green-eyed patients were found to be at higher risk of radiation-induced hearing loss. Eye color does not appear to play a role in hearing loss in non-exposed individuals or presbycusis. It is possible that dark-eyed individuals, with greater inner ear melanin content, are better protected against noise-induced hearing loss. Evidence suggests that melanin can be protective against radiation-induced sensorineural hearing loss, but may predispose individuals to cisplatin ototoxicity. Future studies are required to support these conclusions.

The effect of radiotherapy on gentamicin ototoxicity: an animal model.

OBJECTIVE: Patients undergoing radiotherapy (RT) often present with serious bacterial infections requiring the use of antibiotic treatment. Gentamicin is a commonly used aminoglycoside antibiotic, whose ototoxicity remains a major problem in clinical use. The objective of this study was to determine whether radiation exposure can influence gentamicin-induced ototoxicity. STUDY DESIGN: Prospective animal study. SETTING: Animal care facilities of the Montreal Children's Hospital Research Institute. METHODS: Sixteen guinea pigs received low-dose RT unilaterally for 4 weeks (total: 48 Gy). Animals then received low or high doses of gentamicin (40 mg/kg/d and 80 mg/kg/d) for 10 days. The ears were divided into 4 groups: gentamicin 40 mg, gentamicin 80 mg, gentamicin 40 mg + RT, and gentamicin 80 + RT. Auditory brainstem responses and distortion products otoacoustic emissions were assessed at baseline and before and after gentamicin treatment. Cochlear morphology using light and scanning electron microscopy were evaluated. RESULTS: High-dose gentamicin caused significant auditory brainstem response threshold shifts (P = .020), with greater hearing loss in the irradiated ear (difference of 23.6 + 7.5 dB). All animals exposed to high-dose gentamicin had head tilts toward the radiated side. Cochlear morphology revealed the greatest hair cell damage in the gentamicin 80 + RT group followed by gentamicin 80. CONCLUSION: Results suggest that radiation can exacerbate the ototoxicity of gentamicin at high doses.

Assessment of ototoxicity of intratympanic administration of Auralgan in a chinchilla animal model.

OBJECTIVES/HYPOTHESIS: Auralgan (benzocaine and antipyrine) is an over-the-counter otic drug commonly used for otalgia. Nevertheless, there is limited evidence about the effects of the drug on hearing function and cochlear morphology in the presence of a tympanic membrane perforation. The aim of the present study was to assess the cytotoxicity of Auralgan using cultured auditory cells (HEI-OC1) and to examine its effects on hearing function and cochlear morphology after intratympanic administration in a chinchilla model. STUDY DESIGN: Animal experiment. METHODS: Cell viability and DNA labeling assays were conducted to investigate the cytotoxic effect of the drug on cultured auditory cells (HEI-OC1). To examine the possible drug ototoxic effect in vivo, chinchillas received intratympanic injection of Auralgan in one ear, whereas the contralateral control ear received saline. Outcome measures included auditory brainstem response and postmortem cochlear morphology. RESULTS: A dose-dependent toxic effect of Auralgan was noted on cultured cells. Animal experiments showed an inflammatory reaction in the experimental ears and facial paralysis in 80% of the animals on the side receiving transtympanic injection of Auralgan (P < .05). Auditory brainstem response testing demonstrated a 30- to 50-dB hearing threshold shift across all frequencies tested (P < .05). Control ears showed no inflammation or significant threshold shift. Microscopy showed damage to the hair cells and stria vascularis with bleeding in the perilymphatic space in the experimental ears and damage to the hair cells. CONCLUSIONS: Auralgan was cytotoxic to cultured auditory cells. It promoted an inflammatory reaction and seemed to be ototoxic when given via transtympanic injection in an animal model. LEVEL OF EVIDENCE: NA

Assessment of ototoxicity of tea tree oil in a chinchilla animal model.

OBJECTIVE: The aim of the present study is to examine the effects of tea tree oil on hearing function and cochlear morphology after intratympanic administration in a chinchilla animal model. METHODS: Nine chinchillas received intratympanic injection of 3% tea tree oil dissolved in olive oil in one ear, whereas the contralateral control ear received olive oil only. Outcome measures included auditory brainstem responses conducted before treatment and at 10 days and 30 days following the injection. Post-mortem cochlear morphology was assessed using scanning electron microscopy. RESULTS: At 10 and 30 days following the injection, there was no significant change in auditory brain response thresholds at 8, 16, 20 or 25kHz. Scanning electron microscopy imaging showed no damage to auditory hair cells. CONCLUSION: Tea tree oil (3%) does not appear to be ototoxic in a chinchilla animal model. Future preclinical and clinical studies are required to establish the effectiveness of TTO in treating otitis.

The relevance of dosimetry in animal models of cochlear irradiation.

OBJECTIVE: To compare dose measurements of three different irradiation setups for an animal model of unilateral cochlear irradiation using radiochromic films positioned at the cochlear plane. A method of dosimetry is proposed. METHODS: Radiation field simulation was performed to locate the cochlear plane for irradiation experiments using CT scan images. Fifteen film pieces were irradiated at the cochlear plane with 3 different irradiation field sizes. A 12-mm diameter field (n = 5), 5.7 mm diameter field (n = 5), and a 6.5 × 7.2 mm field (n = 5). After obtaining an ideal irradiation field size, 15 film pieces were used to compare dosimetry between tissue substitute materials (PVC n = 5 and PVC + Teflon, 5 each) and real tissue (frozen animal, n = 5). Auditory brainstem responses at 3 frequencies (8, 16, 20, and 25 kHz) were performed on 7 guinea pigs after a cycle of fractionated unilateral irradiation. RESULTS: Dosimetry in real tissue demonstrated an asymmetric dose distribution at the cochlear plane and ultimately a lower dose deposition (30%) when compared with tissue substitute materials. Auditory brainstem responses of ears subjected to radiotherapy demonstrated progressive hearing loss in long-term assessment. CONCLUSION: Asymmetric dose deposition at the cochlear plane highlights the need of comprehensive real tissue dosimetry in animal studies of cochlear irradiation. To avoid misleading discrepancies in dose-deposition between different studies using the same animal model, appropriate planning and confirmatory dosimetry systems are highly desirable.

Safety and otoprotection of metformin in radiation-induced sensorineural hearing loss in the guinea pig.

OBJECTIVE: There is currently no treatment available to prevent radiation-induced sensorineural hearing loss. Metformin has antineoplastic effects and is able to regulate the mitochondrial production of reactive oxygen species after cellular stress, which is one of the mechanisms involved in apoptosis after radiation damage. The objective of this study was to determine the safety and radioprotective properties of metformin against radiation-induced cochlear damage both in vitro and in vivo. STUDY DESIGN: In vitro and prospective animal study. SETTING: Animal Care Facilities of the Montreal Children's Hospital Research Institute. METHODS: Cultured auditory hair cells (HEI-OC1) were exposed to different concentrations of metformin to determine its safety. Cells were incubated with different metformin concentrations and subjected to radiation. Cell viability after experiments was determined with the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Sixteen guinea pigs were divided in 2 groups: drinking tap water (n = 8) and drinking water containing metformin (n = 8). The animals were unilaterally irradiated for 20 days (total dose 70 Gy), and the ears were divided in 4 groups: control (n = 8), irradiated (n = 8), metformin (n = 8), and experimental (n = 8). Auditory brainstem responses were assessed before and 1, 6, and 16 weeks after completion of radiotherapy. RESULTS: Metformin was not cytotoxic or radioprotective in cultured auditory hair cells. Experimental ears had less hearing loss than radiated ones; however, differences were not statistically significant (P > .05). CONCLUSION: Metformin is not ototoxic or radioprotective in vitro or in vivo. Ears solely subjected to metformin had better hearing thresholds than the rest of the groups.

Mechanisms of radiation-induced sensorineural hearing loss and radioprotection.

Patients that receive radiotherapy are at risk of late sensorineural hearing loss when the inner ear is included within the radiation field. Preclinical and human temporal bone studies have shown that there is differential damage to cochlear structures depending on the amount of dose delivered to the inner ear. In vitro studies have suggested that reactive oxygen species (ROS) are the main initial actors in radiation-induced damage. The interaction of ROS with different cellular components can result in different apoptotic pathways. Therefore, approaches to radioprotection are mainly aimed to reduce ROS production through antioxidants. This review summarizes recent research in the field that can improve the understanding and boost preventive efforts of this adverse effect.

The effect of fractionated radiotherapy in sensorineural hearing loss: an animal model.

OBJECTIVES/HYPOTHESIS: The purpose of this study is to assess the effect of fractionated radiotherapy on sensorineural hearing loss using an animal model. STUDY DESIGN: In vivo animal study. METHODS: Ears of 25 guinea pigs were divided into three groups: control, irradiated with a total of 48 gray (Gy), and 71 Gy. Unilateral exposure of 48 Gy and 71 Gy fractionated irradiation was given for a 4-week period. Auditory brainstem response and distortion products otoacoustic emissions (DPOAE) were tested prior to irradiation and 1, 6, 10, and 16 weeks after completion of radiotherapy to assess the hearing threshold shift postradiotherapy over time. RESULTS: No significant differences in hearing thresholds between the low dose radiation (48 Gy) and the control group (no radiation) underlined that 48 Gy caused no hearing deficits (P = 0.37). The higher dose (71 Gy) showed progressive deterioration of the hearing function over time. Three-way ANOVA interactions revealed significant group-time effects (F= 9.261; P < 0.0001). DPOAE analysis demonstrated hearing loss at 71 Gy without progression or recovery at all time points, predominantly in the higher frequencies tested. CONCLUSION: The present study suggests that in the presence of sensorineural hearing loss due to high- dose fractionated radiotherapy, there is an initial sensorial component; however, the neural component is responsible for its progressivity.