Ototoxicity Research Articles

Drug Induced Ototoxicity

Se define ototoxicidad a las perturbaciones transitorias o definitivas de la funcion auditiva, vestibular, o de las dos a la vez, inducidas por sustancias de uso terapeutico1. Son muchos los trabajos de investigacion que se han dedicado ha este tema quedando aun dudas por resolver debido a las complejas consecuencias donde esta envuelto el dano cocleovestibular. El proposito de esta revision, es presentar las ultimas teorias que tratan de explicar desde el punto de vista de la farmacocinetica/farmacodinamia, biologia celular y molecular el mecanismo por el cual actuan los farmacos involucrados. Lo anteriormente senalado tiene como fin que los ultimos adelantos en esta materia, permitan una mejor comprension que nos lleve a una practica clinica mas segura con relacion a la ototoxicidad medicamentosa, dando a conocer los cuidados y precauciones que se deben tomar antes de administrar un farmaco que se reconoce ototoxico, que puede tener graves consecuencias en la calidad de vida de nuestros pacientes. Palabras clave: Ototoxicidad, toxicidad vestibular, toxicidad coclear, medicamentos ototoxicos.

Drug Induced Ototoxicity � Reply

Drug Induced Ototoxicity � Reply

Ototoxicity in tuberculosis treatment in South Africa: Exploring the current status

As a result of the known ototoxic effects of some of the medications used for tuberculosis (TB) treatment, healthcare workers involved in treating TB patients need to be aware of the ototoxic signs and when to refer to an audiologist for hearing monitoring. The main objective of the present paper was to determine the knowledge and management of ototoxicity related to TB treatment by South African healthcare workers. Telephonic interviews using a semi-structured interview schedule consisting of closed- and open-ended questions were conducted on 100 healthcare workers involved in the treatment of patients with TB. Findings were collated and analyzed via thematic analysis and quantitative descriptive statistics procedures. A large percentage of participants were not aware of what ototoxicity is and what the role of the audiologist was in the management of TB patients. All participating public health facilities do not work with an audiologist as a member of the team in the management of TB patients, and a stark lack of ototoxicity monitoring programs exists. Results highlight the need for education of health-care workers as well as patients regarding ototoxicity. Additionally, audiologists need to become more involved in establishing and implementing ototoxicity monitoring programs in facilities where ototoxic medications are prescribed. Key words: Aminoglycosides, ototoxicity, tuberculosis, health care.

Prenatal screening and diagnosis of genetic deafness by microarray

To evaluate a microarray-based mutation screening method for genetic deafness and its application in prenatal diagnosis. Mutation screening of common deafness genes was performed in pregnant women and volunteers spouses. Nine common mutations in four major deafness genes, GJB2, GJB3, SLC26A4 and mitochondrial 12S rRNA, were detected simultaneously by a microarray-based method. Genetic counseling was given based on their testing results. 5.11% of pregnant women carried at least one mutation. Among them, seven carried mutation in the mitochondria 12S rRNA gene and were offered aminoglycoside-induced ototoxicity warning. For other mutation carriers of GJB2 or SLC26A4 genes, additional mutation screening was performed in their husbands by direct sequencing. A total of 20 couples were at risk of giving birth to children with genetic deafness. Of five couples who selected to undergo prenatal diagnostic testing of the fetus, four were diagnosed as wild type or heterozygous for the tested genes and one as p.V37I/c.235delC compound heterozygous for GJB2. DNA microarray is a quick, easy and reliable method to screen mutations in genetic deafness genes. Application of this method in prenatal screening and diagnosis might effectively reduce the occurrence of genetic deafness.

Gentamicin and ototoxicity: why this drug is still in use

Gentamicin and ototoxicity: why this drug is still in use

Inner ear morphological study of guinea pigs with acoustically evoked short latency negative response

To establish a model of ototoxicity in guinea pigs with acoustically evoked short latency negative response (ASNR) and verify the responsible organ of ASNR based on microscopic characteristics of basal membranes, saccules, utricles and ampulla canalis semicircularis of the inner ear. Total of 45 guinea pigs were employed in the experiment, which were randomly divided into the control group (15 subjects, 30 ears) and the deafened group (30 subjects, 60 ears). Each animal experienced auditory brainstem response (ABR). A quick treatment was employed for deafened group consisting of a subcutaneous injection of kanamycin at a dose of 400 mg/kg followed by jugular vein injection of ethacrynic acid at a dose of 40 mg/kg one hour later. The animals were performed ABR test from 7 to 10 days after the drug administration. The deafened group was further divided into ASNR group and non-ASNR group based on the presence of ASNR. All the guinea pigs were sacrificed after ABR tests. The Corti organ, macula sacculi, macula utriculi and crista ampullaris were observed by light microscope. In the deafened group (60 ears), 3 subjects died postoperatively, 27 subjects (54 ears) provided full data. ASNR was elicited in 19 ears (35.2%, 19/54), the thresholds of ASNR were from 110 to 125 dBSPL with average of (121.7 ± 4.5) dBSPL. ASNR latency ranges were 1.80 - 2.08 ms, the average latency of thresholds were (1.93 ± 0.07) ms. The stretched preparation results: overall hair-cell density of macula saccule, macula utriculi and crista ampullaris decreased in order of normal control group, ASNR group and non-ASNR group. There was no difference between the normal group and ASNR group for cell density of macula saccule. Apart from this, statistical differences were found among other groups. The present study evoked ASNR in an ototoxicity guinea pig model which was profound hearing loss with normal saccular function and normal saccular hair cell density. It suggested that ASNR originates from the saccule and have no relation with cochlear, utricle and semicircular canal according to morphological study.

Ephrin A2 protein expression in the regeneration and plasticity of cochlear hair cells in chicken following kanamycin ototoxicity.

The results from this study showed that the thresholds of brainstem auditory-evoked potentials peak following 10 successive days of intramuscular injection of Roman chickens with kanamycin, starting 3 days after birth. Fluorescence immunohistochemistry analysis revealed few ganglion cells positively labeled for Ephrin A2 in the cochlea of experimental chickens from 2 days before until 7 days after the last kanamycin injection. The number of Ephrin A2-positive ganglion cell bodies was increased at 15 days after the last injection and was similar to that in normal chickens at 30 days following the cessation of kanamycin treatment. These experimental findings indicate that Ephrin A2 protein expression in the acoustic ganglia is synchronized with the connection damage and regeneration of cochlear hair cells after kanamycin exposure. Ephrin A2 may play an important role in the regeneration and plasticity of cochlear hair cells in the chick cochlea following kanamycin ototoxicity.

Roles of heme oxygenase 1 in the protection of H2S against cisplatin- induced injuries in auditory cells

Objective To explore the roles of beme oxygenase 1 ( HO-1 ) in the protection of hydrogen sulfide ( H2S ) against cisplatin-induced injuries in auditory cells.Methods Auditory cells were treated with cisplatin to establish a chemotherapeutics-inducel ototoxicity model.Sodium hydrosulfide ( NaHS,a H2S donor )was added into medium for 1 h before cisplatin treatment.To inhibit the role of HO-1,zine protoporphyrin IX ( ZnPPIX )was used at the time of treatment with NaHS and cisplatin.Cell viabihty was tested by using the cell counting kit ( CCK-8 ).Level of intercellular MDA was detected by a commercial kit.The expressions of HO-1 and cleaved caspase-3 were detected by Western blot.Apoptotic rate was determined by propidium iodide staining and flow cytometry.Results Cisplatin at 10～80 μmol/L for 24h significantly induced cytotoxicity,reducing cell viability.Treatment with cisplatin of 40 μmol/L for 24 hincreased the level of intercellular MDA,expression of cleaved caspase-3,and rate of cellular apoptosis.Pretreatment with NaHS at different concentrations dramatically attenuated the decrease in cell viability induced by cisplatin,and also inhibited an increase in intercellular MDA level,expression of cleaved caspse-3,and rate of apoptosis induced by cisplatin.By inhibiting the role of HO-1,ZnPPIX blocked the inhibitory effects of H2S on an increase in intercellular M DA induced by cisplatin,overexpression of cleaved caspase-3,and apoptosis.Conclusions HO-1 may mediate auditory cells protection of H2S via inhibiting oxidative stress and cisplatin- induced apoptosis. Key words: Heme oxygenase 1; Hydrogen sulfide; , Cisplatin; Oxidative stress; Auditory cells

Influence of Fosfomycin to Aminoglycoside Induced Ototoxicity

Influence of Fosfomycin to Aminoglycoside Induced Ototoxicity

Origin of acoustically evoked short latency negative response in guinea pigs

To establish a model of acoustically evoked short latency negative response (ASNR) in guinea pigs, a model of profound hearing loss with normal saccular functions, and verify the correlation between ASNR and vestibular evoked myogenic potential (VEMP). Thirty-two healthy guinea pigs were employed in the experiment, which were randomly divided into control group (16 subjects) and deafened group (16 subjects). Each animal experienced auditory and vestibular tests including auditory brainstem response (ABR), VEMP and caloric test. A quick treatment was employed for deafened group consisting of a subcutaneous injection of kanamycin at a dose of 400 mg/kg followed by a jugular vein injection of ethacrynic acid at a dose of 40 mg/kg one hour later. The animals were received ABR, VEMP and caloric test 7 - 10 days following the drug administration. The deafened group was further divided into ASNR group and non-ASNR group, based on the presence of ASNR. In deafened group, five subjects died postoperatively, 11 subjects (22 ears) provided full data, ASNR was elicited in eight ears (36.4%), the threshold was 120 - 130 dB SPL with mean of (124.4 ± 4.96) dB SPL. Its latency range was 1.75 - 2.60 ms with mean of (2.15 ± 0.27) ms. The mean latency of threshold was (2.34 ± 0.18) ms. All eight ASNR ears presented with VEMP. The VEMP threshold, positive and negative potential latencies proved no statistical difference (P > 0.05) between ASNR group and control group. Significant difference was detected between the VEMP presence of ASNR group and non-ASNR group (P = 0.002). There was no statistically significant correlation between VEMP and caloric test neither between ASNR and caloric test in deafened group. This study evoked ASNR in an ototoxicity guinea pig model which has profound hearing loss with normal saccular functions. The presence of ASNR correlated with VEMP, however, not correlated with caloric test, suggesting that ASNR and VEMP are both originated from the saccule.

Is There an Association Between 5‐Azacitidine and Ototoxicity?

Is There an Association Between 5‐Azacitidine and Ototoxicity?

Protection of cochlear function from aminoglycosides ototoxicity by manganese superoxide dismutase gene in aging rat

determine the feasibility of manganese superoxide dismutase (MnSOD) gene therapy for protecting the cochlear function against aminoglycoside-induced oxidative stress in aging rats. The aging model of SD rats were obtained with 8 weeks daily of D-gal (150 mg/kg per day) hypodermic injection. In the 9th week, amikacin (500 mg/kg per day) were injected intramuscularly into some aging SD rats. The viral particles of recombinant adeno-associated viral vector II/MnSOD (6 microl, 5 x 10(11) vector genomes/ml) were injected into the perilymph through the round window membrane (RWM). The feasibility of MnSOD gene therapy against aminoglycoside-induced oxidative stress in aging rats was evaluated with the methods of caspase-3 protein analysis, apoptosis detection with immunohistochemical, the detection of MnSOD concentration, stretched preparation of basilar membrane and evaluation of hearing threshold with ABR-click. Compared with the control group, the concentration of MnSOD of cochlear tissue was increased (P < 0.05), and the active fragment expression of caspase-3, the numbers of apoptosis bodies and the hearing threshold were decreased (P < 0.05). MnSOD could play a partly role to treat cochlear aminoglycoside-induced oxidative damage in aging rats.

Assessment of the occupational ototoxicity of n-hexane

Assessment of the occupational ototoxicity of n-hexane

The ototoxicity of intratympanic injection gentamycin and the protection effect of ciwujia

目的 探讨豚鼠局部应用用庆大霉素的耳蜗毒性作用,以及刺五加有无减轻庆大霉素耳蜗毒性的作用.方法 选择健康豚鼠44只,随机分为三组:Ⅰ为庆大霉素组,Ⅱ为庆大霉素+刺五加组,Ⅲ为生理盐水组;采用鼓膜穿刺法向豚鼠鼓室内注射药物,Ⅱ组同时腹腔注射刺五加注射液;给药2周后检测三组动物的脑干诱发电位(ABR)的阈值变化,并取三组动物耳蜗底周标本行耳蜗铺片及切片,扫描及透射电镜检查.结果 给药后Ⅰ组ABR阈值与Ⅱ组差异有显著性(P<0.01),耳蜗形态学观察示Ⅱ组毛细胞受损程度较Ⅰ组为轻.结论 豚鼠鼓室内注射庆大霉素具有明显的耳蜗毒性,联合应用中药刺五加具有对抗庆大霉素耳毒性的作用。

Aminoglycosides: ototoxicity more severe with m.1555A&gt;G mutation

Aminoglycosides: ototoxicity more severe with m.1555A&gt;G mutation

Aminoglycosides: ototoxicity more severe with m.1555A&gt;G mutation

Aminoglycosides: ototoxicity more severe with m.1555A&gt;G mutation

Vancomycin-Induced Thrombocytopenia

Red man syndrome, hypersensitivity reactions, neutropenia, nephrotoxicity, and ototoxicity are well-recognized side effects of vancomycin. Now,

Evolução da perda auditiva no decorrer do envelhecimento

A perda auditiva associada ao envelhecimento refere-se à soma de perdas auditivas resultantes da degeneração fisiológica causada por exposição ao ruído, agentes ototóxicos e prejuízos causados por desordens e tratamentos médicos. Afeta cerca de 60% de todas as pessoas com idade acima de 65 anos. OBJETIVO: Verificar a degeneração do sistema auditivo no decorrer da idade através de medidas supraliminares e de sensibilidade auditiva. MATERIAL E MÉTODO: Estudo de coorte contemporânea com corte transversal. Foram avaliados 211 idosos, com idade média de 75,24 anos, sendo 61 do sexo masculino e 150 do sexo feminino. Os indivíduos foram submetidos a uma anamnese e à avaliação audiológica básica e divididos em quatro grupos, de acordo com a faixa etária. RESULTADOS: Declínio significativo do limiar nas 4 faixas etárias estabelecidas, diminuição do índice percentual de reconhecimento de fala, diferença significante com relação ao gênero. CONCLUSÃO: Com o avanço da idade, ocorreu um aumento gradual no grau da perda auditiva, os homens apresentaram limiares mais rebaixados na freqüência de 4000Hz em comparação com as mulheres e na inteligibilidade de fala observou-se decréscimo gradativo com o aumento da idade.

Detection of late ototoxic side effect of cisplatin by distortion otoacoustic emission (DPOAE)

Cisplatin-based chemotherapy results in high cure rate in testicular cancer. The issue of toxicity is of special concern in young men with a probability of cure of at least 70-80% even in disseminated disease. As the literature shows, the ototoxic side effects of cisplatin have been studied mostly by conventional method. The authors used distortion product otoacoustic emission to detect the long-term ototoxic effect of cisplatin in 223 patients with a median follow-up time of 4.27 years (range 0.5-20 years) and a median age of 37 years (range 18-55 years). Cisplatin (20 mg/m(2) body surface) was administered for five days per cycle, in combination with other antitumor drugs. The control group consisted of 40 testicular cancer patients who did not receive chemotherapy, with a median age of 35 years (range 16-54 years). A detailed medical history based on a standardized questionnaire evaluated hearing complaints and audiological risk factors, such as head injuries, chronic otitis media, previous noise exposure and familial hearing loss. DPOAE was measured at 8 frequencies from 750 to 8000 Hz. No amplitude changes were detected in patients receiving =300 mg/m(2) cisplatin. At higher doses, contrary to the literature, not only high frequencies were affected: our method could detect significant hearing impairment at lower frequencies important for speech perception in patients receiving at least 400 mg/m(2) cisplatin. The lower frequencies where significant amplitude changes were detected were 3000 Hz at 400 mg/m(2), and 1500, 2000 and 3000 Hz at 500-600 mg/m(2). We detected the worst hearing in the case of patients who had symptomatic ototoxicity. Age and the cumulative dose of cisplatin proved statistically significant risk factors, while smoking or noise exposure did not have predictive value. As a conclusion, DPOAE is a fast, noninvasive and reliable method for the detection of late ototoxicity in testicular cancer patients. In our study hearing loss correlated with the cumulative dose of cisplatin. Hearing impairment contributes to the already compromised situation of cancer patients.

Large-scale screening of mtDNA A1555G mutation in China and its significance in prevention of aminoglycoside antibiotic induced deafness

To explore the necessity of large-scale screening of mtDNA A1555G mutation in prevention of aminoglycoside antibiotic induced deafness (AAID) and to develop a feasible method to prevent AAID. A total of 1836 patients with non-syndromic hearing impairment (NSHI), 1352 students of schools for deaf-mutes in 11 provinces and municipality in China, 413 out-patients, and 71 persons from the families with maternal relatives suffering from AAID, underwent questionnaire survey and/or PCR for A-to-G mutation at nucleotide 1555 of the mitochondrial genome. Sixty three patients with mtDNA A1555G mutation were found among the 1836 NSHI patients. Fifty-two maternal pedigrees were identified. 536 cases with normal hearing from these pedigrees were informed to avoid using aminoglycoside antibiotics (AmAn). Large-scale screening of mtDNA A1555G mutation and relevant health education to avoid use of AmAn are effective to prevent ototoxicity in the A1555G carriers and their maternal relatives.