Gentamicin-Induced Chronotoxicity: Use of Body Temperature as a Orcadian Marker Rhythm

Aminoglycoside antibiotics produce varying degrees of ototoxicity, dependent on dosage time, in animals synchronized for rhythm study. Herein, we illustrate the use of an economical and reliable system to telemeter body temperature of laboratory animals as an endogenous marker rhythm for gentamicin-induxed ototoxicity. Two groups of 3 male Sprague-Dawley rats (250–400 gm) were housed in separate cages in a temperature-controlled room programmed with a 12:12 LD schedule and monitored for hearing thresholds at the frequencies of 8kHz, 16kHz, 24kHz and 32kHz at 2-week intervals. Each rat was dosed with 100 mg/kg/day gentamicin subcutaneously for a duration of 28 days. The animals from one group were dosed at their daily temperature maximum, while the animals of the other group were dosed at their daily temperature minimum. Both after 14 and 28 days of gentamicin treatment there was no important changes in auditory thresholds from baseline values when treatment was timed daily to the circadian peak of body temperature. Animals dosed daily at the trough of the circadian temperature rhythm evidenced an auditory threshold shift of between 5 and 25 dB after 14 days of treatment and a total hearing loss (80–90 dB) after 28 days of such treatment. These results document a dramatically greater level of hearing loss induced in those animals dosed with gentamicin at the body temperature trough (diurnal rest span) as compared to those dosed at the acrophase (nocturnal activity span). The findings indicate that the peak and trough of the circadian pattern of body temperature serve as meaningful markers of the resistance and susceptibility, respectively, of gentamicin-induced ototoxicity in rodent models.     

Gentamicin-Induced Chronotoxicity: Use of Body Temperature as a Orcadian Marker Rhythm

Aminoglycoside antibiotics produce varying degrees of ototoxicity, dependent on dosage time, in animals synchronized for rhythm study. Herein, we illustrate the use of an economical and reliable system to telemeter body temperature of laboratory animals as an endogenous marker rhythm for gentamicin-induxed ototoxicity. Two groups of 3 male Sprague-Dawley rats (250-400 gm) were housed in separate cages in a temperature-controlled room programmed with a 12:12 LD schedule and monitored for hearing thresholds at the frequencies of 8kHz, 16kHz, 24kHz and 32kHz at 2-week intervals. Each rat was dosed with 100 mg/kg/day gentamicin subcutaneously for a duration of 28 days. The animals from one group were dosed at their daily temperature maximum, while the animals of the other group were dosed at their daily temperature minimum. Both after 14 and 28 days of gentamicin treatment there was no important changes in auditory thresholds from baseline values when treatment was timed daily to the circadian peak of body temperature. Animals dosed daily at the trough of the circadian temperature rhythm evidenced an auditory threshold shift of between 5 and 25 dB after 14 days of treatment and a total hearing loss (80-90 dB) after 28 days of such treatment. These results document a dramatically greater level of hearing loss induced in those animals dosed with gentamicin at the body temperature trough (diurnal rest span) as compared to those dosed at the acrophase (nocturnal activity span). The findings indicate that the peak and trough of the circadian pattern of body temperature serve as meaningful markers of the resistance and susceptibility, respectively, of gentamicin-induced ototoxicity in rodent models.     

Gentamicin-induced ototoxicity and nephrotoxicity vary with circadian time of treatment and entail separate mechanisms

The aminoglycoside antibiotic gentamicin can cause both ototoxicity and nephrotoxicity, the severity of which varies with circadian time of daily treatment. However, it is not yet resolved if such drug-induced adverse effects are independent or interdependent phenomena. Two groups of 9 female Sprague-Dawley rats (200–250?g), each housed separately and entrained to a 12?h light (06:00–18:00?h) – 12?h dark cycle, received a daily subcutaneous injection of 100?mg/kg gentamicin. One group was treated at the beginning of the activity span, 2 Hours After Lights On (HALO), and the other at the beginning of the rest span, 14 HALO. Global toxicity was gauged by both body weight loss relative to the pre-treatment baseline and number of deaths. Ototoxicity, i.e., hearing loss, was assessed by changes in auditory brainstem response (ABR) for pure tone stimuli of 8, 16, 24, and 32?kHz before and after 2 and 4 weeks of gentamicin treatment. Renal toxicity was evaluated by changes in urinary N-acetyl-β-glucosaminidase (NAG)/creatinine (CR) concentration ratio before and after each week of treatment. In a complementary substudy of separate but comparable 2 and 14 HALO groups of rats, blood samples were obtained before and 30, 60, 120, and 240?min post-subcutaneous injection of 100?mg/kg gentamicin. Number of animal deaths was greater in the 2 (4 deaths) than 14 HALO (1 death) group, mirroring more severe initial (first two weeks of treatment) body weight losses from baseline, being more than 2-fold greater in animals of the 2 than 14 HALO group. Ototoxicity progressively worsened during the treatment; although, the extent of hearing loss varied according to circadian time of treatment across all frequencies (p?<?0.05), particularly the 24 and 32?kHz ones (both p?<?0.005), both at the 2 and 4 week assessments. At 32?kHz after 4 weeks of gentamicin dosing, the 2 HALO group showed an average 42?dB hearing loss, while the 14 HALO group exhibited only an average 10?dB loss. ABR response latencies were longer for the 2 than 14 HALO rats. The time course of nephrotoxicity differed from that of ototoxicity. The mean urinary NAG/CR ratio peaked after the first week of treatment, averaging 13.64-fold greater than baseline for the 2 HALO-treated animals compared to 7.38-fold greater than baseline for the 14 HALO-treated ones. Ratio values declined thereafter; although, even after the second week of dosing, they remained greater in the 2 than 14 HALO group (averaging 8.15-fold greater and 2.23-fold greater than baseline, respectively). Pharmacokinetic analysis of the blood gentamicin values revealed slower clearance, on average by ～25% (p?<?0.001), in the rats of the 14 than 2 HALO group (x?±?S.E.: 3.22?±?0.49 and 4.53?±?0.63?mL/min/kg, respectively). The study findings indicate robust difference of the time course in rats of both treatment groups of gentamicin-induced ototoxicity and nephrotoxicity, supporting the hypothesis these organ toxicities are independent of one another, and further suggest the observed treatment-time differences in gentamicin adverse effects may be more dependent on local cell, tissue, or organ circadian (chrono) pharmacodynamic than (chrono) pharmacokinetic mechanisms.     

Psychophysical and neurophysiological hearing thresholds in the bat <Emphasis Type="Italic">Phyllostomus </Emphasis><Emphasis Type="Italic">discolor</Emphasis>

Absolute hearing thresholds in the spear-nosed bat Phyllostomus discolor have been determined both with psychophysical and neurophysiological methods. Neurophysiological data have been obtained from two different structures of the ascending auditory pathway, the inferior colliculus and the auditory cortex. Minimum auditory thresholds of neurons are very similar in both structures. Lowest absolute thresholds of 0 dB SPL are reached at frequencies from about 35 to 55 kHz in both cases. Overall behavioural sensitivity is roughly 20 dB better than neural sensitivity. The behavioural audiogram shows a first threshold dip around 23 kHz but threshold was lowest at 80 kHz (−10 dB SPL). This high sensitivity at 80 kHz is not reflected in the neural data. The data suggest that P. discolor has considerably better absolute auditory thresholds than estimated previously. The psychophysical and neurophysiological data are compared to other phyllostomid bats and differences are discussed. S. Hoffmann, L. Baier, F. Borina contributed equally to this work.     

Cigarette Smoking Causes Hearing Impairment among Bangladeshi Population

Lifestyle including smoking, noise exposure with MP3 player and drinking alcohol are considered as risk factors for affecting hearing synergistically. However, little is known about the association of cigarette smoking with hearing impairment among subjects who carry a lifestyle without using MP3 player and drinking alcohol. We showed here the influence of smoking on hearing among Bangladeshi subjects who maintain a lifestyle devoid of using MP3 player and drinking alcohol. A total of 184 subjects (smokers: 90; non-smokers: 94) were included considering their duration and frequency of smoking for conducting this study. The mean hearing thresholds of non-smoker subjects at 1, 4, 8 and 12 kHz frequencies were 5.63±2.10, 8.56±5.75, 21.06±11.06, 40.79±20.36 decibel (dB), respectively and that of the smokers were 7±3.8, 13.27±8.4, 30.66±12.50 and 56.88±21.58 dB, respectively. The hearing thresholds of the smokers at 4, 8 and 12 kHz frequencies were significantly (p<0.05) higher than those of the non-smokers, while no significant differences were observed at 1 kHz frequency. We also observed no significant difference in auditory thresholds among smoker subgroups based on smoking frequency. In contrast, subjects smoked for longer duration (>5 years) showed higher level of auditory threshold (62.16±19.87 dB) at 12 kHz frequency compared with that (41.52±19.21 dB) of the subjects smoked for 1-5 years and the difference in auditory thresholds was statistically significant (p<0.0002). In this study, the Brinkman Index (BI) of smokers was from 6 to 440 and the adjusted odds ratio showed a positive correlation between hearing loss and smoking when adjusted for age and body mass index (BMI). In addition, age, but not BMI, also played positive role on hearing impairment at all frequencies. Thus, these findings suggested that cigarette smoking affects hearing level at all the frequencies tested but most significantly at extra higher frequencies.     

Effect of Different Gentamicin Dose on the Plasticity of the Ribbon Synapses in Cochlear Inner Hair Cells of C57BL/6J Mice

Faithful information transfer at the hair cell afferent synapse requires synaptic transmission to be both reliable and temporally precise. The release of neurotransmitter must exhibit both rapid on and off kinetics to accurately follow acoustic stimuli with a periodicity of 1?ms or less. To ensure such remarkable temporal fidelity, the cochlear hair cell afferent synapse undoubtedly relies on unique cellular and molecular specializations. To study effects of different doses of gentamicin on the changes of synaptic ribbons of cochlear inner hair cells (IHCs) in mice, the availability of genetic information, transgenic and knock-out animals make the C57BL/6J mouse a primary model in biomedical research. Aminoglycoside ototoxicity, however, has rarely been studied in mature mice because they are considered highly resistant to the drugs. This study presents models for gentamicin ototoxicity in adult C57BL/6J mouse strains. Five-week-old mice were injected intraperitoneally once daily with 50?C300?mg gentamicin base/kg body weight for 7?days. Higher doses of gentamicin appear to be associated with earlier hearing damage in C57BL/6J mice, although not necessarily with more severe damage. At 200?mg/kg, gentamicin appears to induce significant hearing damage while not significantly affect the animal??s general condition. Therefore, 200?mg/kg may be an ideal dose for ototoxicity modeling in C57BL/6J mice using gentamicin. In the early period of different dose of gentamicin effect, when the number of hair cells had not changed, the number changes of IHC ribbon synapses had taken place. Through the number of ribbon synapses changing, IHCs increased or decreased connections with spiral ganglion nerves (SGNs). The ribbon synapses played a compensatory role for gentamicin ototoxicity, while this effect was not sufficient to maintain the normal threshold of hearing.     

Effects of Boat Engine Noise on the Auditory Sensitivity of the Fathead Minnow, Pimephales promelas

Fishes are constantly exposed to various sources of noise in their underwater acoustic environment. Many of these sounds are from anthropogenic sources, especially engines of boats. Noise generated from a small boat with a 55 horsepower outboard motor was played back to fathead minnows, Pimephales promelas, for 2 h at 142 dB (re: 1 Pa), and auditory thresholds were measured using the auditory brainstem response (ABR) technique. The results demonstrate that boat engine noise significantly elevate a fish's auditory threshold at 1 kHz (7.8 dB), 1.5 kHz (13.5 dB), and 2.0 kHz (10.5 dB), the most sensitive hearing range of this species. Such a short duration of noise exposure leads to significant changes in hearing capability, and implies that man-made noise generated from boat engines can have far reaching environmental impacts on fishes.     

The development of hearing sensitivity in altricial birds: the absolute thresholds of the generation of evoked potentials]

Thresholds of field L auditory evoked potentials EP were studied in 1.5-9-day-old nestlings of pied flycatcher in response to pure tone signals of different frequencies. According to the tendencies of age dynamics of auditory EP thresholds (2-9 days of life) all hearing range was divided into three separate channels: low-frequency (0.3-1.0 kHz), intermediate-(1.5-4.0 kHz) and high-frequency (5.0-8.0 kHz) ones. The widening of the hearing range in its high-frequency part was demonstrated on days 4-5 of life. The development of auditory sensitivity was shown to continue within all three channels in postembryonic period (days 2-9 post-hatching), each of the channels being characterized by its own age dynamics of auditory EP thresholds. Reproduction of tape-recorded species song during days 1-3 post-hatching resulted in significant decrease of auditory EP thresholds.     

The effects of noise on the auditory sensitivity of the bluegill sunfish,Lepomis macrochirus

As concerns about the effects of underwater anthropogenic noises on the auditory function of organisms increases, it is imperative to assess if all organisms are equally affected by the same noise source. Consequently, auditory capabilities of an organism need to be evaluated and compared interspecifically. Teleost fishes provide excellent models to examine these issues due to their diversity of hearing capabilities. Broadly, fishes can be categorized as hearing specialists (broad hearing frequency range with low auditory thresholds) or hearing generalists (narrower frequency range with higher auditory thresholds). The goal of this study was to examine the immediate effects of white noise exposure (0.3-2.0 kHz, 142 dB re: 1 microPa) and recovery after exposure (1-6 days) on a hearing generalist fish, bluegill sunfish (Lepomis macrochirus). Noise exposure resulted in only a slight, but not statistically significant, elevation in auditory threshold compared to fish not exposed to noise. In combination with results from our previous studies examining effects of noise on a hearing specialist fish, the fathead minnow (Pimephales promelas), this study provides evidence supporting the hypothesis that fish's auditory thresholds can be differentially affected by noise exposure.     

Effects of Temperature on Auditory Sensitivity in Eurythermal Fishes: Common Carp Cyprinus carpio (Family Cyprinidae) versus Wels Catfish Silurus glanis (Family Siluridae)

Background

In ectothermal animals such as fish, -temperature affects physiological and metabolic processes. This includes sensory organs such as the auditory system. The reported effects of temperature on hearing in eurythermal otophysines are contradictory. We therefore investigated the effect on the auditory system in species representing two different orders.

Methodology/Principal Findings

Hearing sensitivity was determined using the auditory evoked potentials (AEP) recording technique. Auditory sensitivity and latency in response to clicks were measured in the common carp Cyprinus carpio (order Cypriniformes) and the Wels catfish Silurus glanis (order Siluriformes) after acclimating fish for at least three weeks to two different water temperatures (15°C, 25°C and again 15°C). Hearing sensitivity increased with temperature in both species. Best hearing was detected between 0.3 and 1 kHz at both temperatures. The maximum increase occurred at 0.8 kHz (7.8 dB) in C. carpio and at 0.5 kHz (10.3 dB) in S. glanis. The improvement differed between species and was in particular more pronounced in the catfish at 4 kHz. The latency in response to single clicks was measured from the onset of the sound stimulus to the most constant positive peak of the AEP. The latency decreased at the higher temperature in both species by 0.37 ms on average.

Conclusions/Significance

The current study shows that higher temperature improves hearing (lower thresholds, shorter latencies) in eurythermal species from different orders of otophysines. Differences in threshold shifts between eurythermal species seem to reflect differences in absolute sensitivity at higher frequencies and they furthermore indicate differences to stenothermal (tropical) species.     

Characterization of beam patterns of bottlenose dolphin in the transversal plane

The characteristics of the absolute auditory sensitivity of the bottlenose dolphin (Tursiops truncatus p.) in the transverse plane have been measured using short broad-band stimuli simulating dolphin clicks (with energy maximum at frequencies 8, 16, 30, 50 and 100 kHz). Experiments were performed using the method of conditioned reflexes with food reinforcement. It was shown that, in the frequency range of 8-30 kHz, the absolute sensitivity of dolphin hearing in any ventral and lateral directions of the transverse plane is only by 2-8 dB worse than in the nasal direction. Moreover, it is approximately by 25-30 dB better than at frequencies of 50-100 kHz. At frequencies of 8-30 kHz, a pronounced dorsoventral asymmetry has been observed. In this frequency range, it reaches approximately 15-18 dB whereas at frequencies of 50-100 kHz, this asymmetry decreases to 2-3 dB. In the dorsal direction, the auditory sensitivity is by 18 dB worse than in the nasal one at frequencies of around 8 kHz, and the difference rises smoothly to 33 dB at frequencies of about 100 kHz. At frequencies of 50-100 kHz, the acoustical thresholds of the cross-section plane in comparison with thresholds for the with nasal direction get worse almost uniformly in all directions by 25-33 dB. As a result, in the transversal plane, the beam patterns have a nearly circular form, unlike the patterns at frequencies of 8-30 kHz. The results are discussed in terms of the model of sound perception through the left and right mental foramens. The biological expediency of the asymmetry is emphasized.     

Circadian modulation of starvation-induced hypothermia in sheep and goats

Prolonged food deprivation is known to cause a fall in the core body temperature of homeotherms. In various species of small birds and mammals (body mass up to 2–3 kg), it has been shown that starvation-induced hypothermia is modulated by the circadian system, in the sense that hypothermia is observed primarily during the inactive phase of the daily activity cycle (i.e., during the night for diurnal animals and during the day for nocturnal animals), whereas relatively normal temperatures are recorded during the active phase. To investigate whether this modulation occurs also in larger animals, we investigated the effects of 4d food deprivation on the body temperature rhythm of goats and sheep (body mass 30–40 kg). In goats, the body temperature rhythm was found to have a mean level of 39.0°C with a mean daily range of excursion of 0.42°C. The daily oscillation in body temperature persisted during the first day of fasting, but the rhythm was drastically damped, if not eliminated, over the next 3 d as body temperature descended from the baseline level of 39.0 to 38.2°C. In sheep, the rhythm was found to have a mean level of 39.3°C with a mean daily range of excursion of 0.34°C. The daily oscillation in body temperature persisted through the 4 d of food deprivation, even though the mean level of body temperature gradually fell. Temperature fell more during the third and fourth nights than during the third and fourth days. Thus, circadian modulation of starvation-induced hypothermia was observed in sheep but not in goats.     

Influence of Feeding Schedule on Chronopharmacological Aspects of Gentamicin in Mice

The effects of the time of day of drug administration on the subchronic toxicity and pharmacokinetics of gentamicin, as well as the role of feeding schedule on circadian rhythms, were investigated in mice. ICR male mice were housed in a light-dark (LD) cycle (12:12) with food and water ad libitum (ALF) or under a time-restricted feeding (TRF) schedule (feeding time: 8 h during the light phase) for 1 day or 14 days before drug administration. The animals were given a single subcutaneous dose of gentamicin 180 mg/kg for the kinetic studies and subcutaneous doses of gentamicin 180 mg/kg/day for 14 days or 220 mg/kg/day for 18 days for the subchronic toxicity studies. A significant dosing-time dependency was shown for mortality and body weight loss, with higher values at midlight and lower ones at the middark (p > 0.05). A significant circadian rhythm was also found for gentamicin kinetics in ALF mice, with the highest clearance at middark and the lowest one at midlight (p > 0.01). The kinetic rhythm of gentamicin coincided well with the toxicity rhythm of the drug. The TRF schedule had a marked influence on the rhythms of gentamicin kinetics and toxicity, showing lowest clearance and higher toxicity at middark. The rhythm of subchronic toxicity of gentamicin seems to be due, at least in part, to the rhythm in kinetics and is strongly influenced by the feeding schedule. Thus, the timing of dosing is an important factor in the kinetics and the subchronic toxicity of gentamicin administration in mice, and the manipulation of feeding schedule can modify the rhythm of the toxicity by changing the rhythm of gentamicin kinetics.     

Effects of simultaneous exercise and loud music on hearing acuity and auditory function

Hearing acuity can be reduced temporarily after exposure to loud noise, and the physiological responses that occur with exercise may enhance this effect. Currently, it is not known whether short-term reductions in hearing acuity after noise exposure and exercise are a result of temporary changes in auditory function. Therefore, the purpose of this investigation was to determine the acute effects of simultaneous exercise and loud music on hearing acuity and auditory function in young, healthy women. Nine women (age = 22 +/- 5 years, body mass index = 23.9 +/- 2.2, Vo(2)peak = 30.6 +/- 6.0 ml x kg(-1) x min(-1)) with normal hearing thresholds (<20 dB hearing level) underwent each of 3 conditions in a randomized counterbalanced design: (a) loud music exposure of 90 to 95 dB sound pressure level for 20 minutes, (b) exercise at 60% Vo(2)peak on a cycle ergometer for 20 minutes, and (c) simultaneous exercise and music exposure for 20 minutes. Hearing acuity and auditory function were assessed via pure-tone hearing thresholds and distortion product otoacoustic emission amplitudes, respectively, at frequencies of 2, 3, 4, 6, and 8 kHz presented in random order before and after each condition. Results indicate that hearing acuity and auditory function remained unaltered after exposure to each condition (p > 0.05). These findings provide evidence that hearing acuity and auditory function in young women do not change after short-term exposure to moderate-intensity exercise and loud music. Thus, listening to loud music with earphones during moderate-intensity exercise does not pose acute hearing health concerns for young physically fit adults with normal hearing.     

Absolute hearing thresholds and critical masking ratios in the European barn owl: a comparison with other owls

Absolute thresholds and critical masking ratios were determined behaviorally for the European barn owl (Tyto alba guttata). It shows an excellent sensitivity throughout its hearing range with a minimum threshold of −14.2 dB sound pressure level at 6.3 kHz, which is similar to the sensitivity found in the American barn owl (Tyto alba pratincola) and some other owls. Both the European and the American barn owl have a high upper-frequency limit of hearing exceeding that in other bird species. Critical masking ratios, that can provide an estimate for the frequency selectivity in the barn owl's hearing system, were determined with a noise of about 0 dB spectrum level. They increased from 19.1 dB at 2 kHz to 29.2 dB at 8 kHz at a rate of 5.1 dB per octave. The corresponding critical ratio bandwidths were 81, 218, 562 and 831 Hz for test-tone frequencies of 2, 4, 6.3 and 8 kHz, respectively. These values indicate, contrary to expectations based on the spatial representation of frequencies on the basilar papilla, increasing bandwidths of auditory filters in the region of the barn owl's auditory fovea. This increase, however, correlates with the increase in the bandwidths of tuning curves in the barn owl's auditory fovea. Accepted: 27 November 1997     

NaHS Protects Cochlear Hair Cells from Gentamicin-Induced Ototoxicity by Inhibiting the Mitochondrial Apoptosis Pathway

Aminoglycoside antibiotics such as gentamicin could cause ototoxicity in mammalians, by inducing oxidative stress and apoptosis in sensory hair cells of the cochlea. Sodium hydrosulfide (NaHS) is reported to alleviate oxidative stress and apoptosis, but its role in protecting aminoglycoside-induced hearing loss is unclear. In this study, we investigated the anti-oxidant and anti-apoptosis effect of NaHS in in vitro cultured House Ear Institute-Organ of Corti 1 (HEI-OC1) cells and isolated mouse cochlea. Results from cultured HEI-OC1 cells and cochlea consistently indicated that NaHS exhibited protective effects from gentamicin-induced ototoxicity, evident by maintained cell viability, hair cell number and cochlear morphology, reduced reactive oxygen species production and mitochondrial depolarization, as well as apoptosis activation of the intrinsic pathway. Moreover, in the isolated cochlear culture, NaHS was also demonstrated to protect the explant from gentamicin-induced mechanotransduction loss. Our study using multiple in vitro models revealed for the first time, the potential of NaHS as a therapeutic agent in protecting against aminoglycoside-induced hearing loss.     

Hearing in Cichlid Fishes under Noise Conditions

Background

Hearing thresholds of fishes are typically acquired under laboratory conditions. This does not reflect the situation in natural habitats, where ambient noise may mask their hearing sensitivities. In the current study we investigate hearing in terms of sound pressure (SPL) and particle acceleration levels (PAL) of two cichlid species within the naturally occurring range of noise levels. This enabled us to determine whether species with and without hearing specializations are differently affected by noise.

Methodology/Principal Findings

We investigated auditory sensitivities in the orange chromide Etroplus maculatus, which possesses anterior swim bladder extensions, and the slender lionhead cichlid Steatocranus tinanti, in which the swim bladder is much smaller and lacks extensions. E. maculatus was tested between 0.2 and 3kHz and S. tinanti between 0.1 and 0.5 kHz using the auditory evoked potential (AEP) recording technique. In both species, SPL and PAL audiograms were determined in the presence of quiet laboratory conditions (baseline) and continuous white noise of 110 and 130 dB RMS. Baseline thresholds showed greatest hearing sensitivity around 0.5 kHz (SPL) and 0.2 kHz (PAL) in E. maculatus and 0.2 kHz in S. tinanti. White noise of 110 dB elevated the thresholds by 0–11 dB (SPL) and 7–11 dB (PAL) in E. maculatus and by 1–2 dB (SPL) and by 1–4 dB (PAL) in S. tinanti. White noise of 130 dB elevated hearing thresholds by 13–29 dB (SPL) and 26–32 dB (PAL) in E. maculatus and 6–16 dB (SPL) and 6–19 dB (PAL) in S. tinanti.

Conclusions

Our data showed for the first time for SPL and PAL thresholds that the specialized species was masked by different noise regimes at almost all frequencies, whereas the non-specialized species was much less affected. This indicates that noise can limit sound detection and acoustic orientation differently within a single fish family.     

EGb 761 (Ginkgo biloba) protects cochlear hair cells against ototoxicity induced by gentamicin via reducing reactive oxygen species and nitric oxide-related apoptosis

Gentamicin is an effective and powerful antibiotic. Extended use or excessive dosages of which can result in irreversible damage to the inner ear. The development of otoprotective strategies is a primary and urgent goal in research of gentamicin ototoxicity. Ginkgo biloba leaves and their extracts are among the most widely used herbal products and/or dietary supplements in the world. We investigated the protection of EGb 761 (a standardized preparation of EGb) on gentamicin ototoxicity and the involvement of reactive oxygen species (ROS) and nitric oxide (NO)-related mechanisms using in vitro organ cultures and an in vivo animal model. Gentamicin induced hair cell damage in cochlear cultures that could be prevented by EGb 761. EGb 761 also significantly reduced gentamicin-induced ROS and NO production. Furthermore, EGb 761 inhibited cellular apoptosis in cultured cochleae treated with gentamicin. In guinea pigs with gentamicin application onto the round window membrane, the mean auditory brain stem response threshold, ratio of cochlear hair cell damage and apoptosis were significantly elevated compared with those in the control group, and this could be prevented by oral administration of EGb 761. Individual EGb 761 components quercetin, bilobalide, ginkgolide A and ginkgolide B, but not kaempferol, significantly prevented gentamicin-induced hair cell damage. These results indicate that EGb 761 has a protective effect against gentamicin ototoxicity through a reduction in the formation of ROS and NO and subsequent inhibition of hair cell apoptosis in the cochlea.     

Circadian modulation of starvation-induced hypothermia in sheep and goats

Prolonged food deprivation is known to cause a fall in the core body temperature of homeotherms. In various species of small birds and mammals (body mass up to 2-3 kg), it has been shown that starvation-induced hypothermia is modulated by the circadian system, in the sense that hypothermia is observed primarily during the inactive phase of the daily activity cycle (i.e., during the night for diurnal animals and during the day for nocturnal animals), whereas relatively normal temperatures are recorded during the active phase. To investigate whether this modulation occurs also in larger animals, we investigated the effects of 4d food deprivation on the body temperature rhythm of goats and sheep (body mass 30-40 kg). In goats, the body temperature rhythm was found to have a mean level of 39.0°C with a mean daily range of excursion of 0.42°C. The daily oscillation in body temperature persisted during the first day of fasting, but the rhythm was drastically damped, if not eliminated, over the next 3 d as body temperature descended from the baseline level of 39.0 to 38.2°C. In sheep, the rhythm was found to have a mean level of 39.3°C with a mean daily range of excursion of 0.34°C. The daily oscillation in body temperature persisted through the 4 d of food deprivation, even though the mean level of body temperature gradually fell. Temperature fell more during the third and fourth nights than during the third and fourth days. Thus, circadian modulation of starvation-induced hypothermia was observed in sheep but not in goats.