The Effects of Riluzole on Cisplatin-induced Ototoxicity

Abstract Introduction Riluzole (2-amino-6-trifluoromethoxy benzothiazole) is known as a neuroprotective, antioxidant, antiapoptotic agent. It may have beneficial effects on neuronal cell death due to cisplatin-induced ototoxicity. Objective To evaluate the effect of riluzole on cisplatin-induced ototoxicity in guinea pigs. Methods Twenty-four guinea pigs, studied in three groups, underwent auditory brainstem response evaluation using click and 8 kHz tone burst stimuli. Subsequently, 5 mg/kg of cisplatin were administered to all animals for 3 days intraperitoneally (i.p.) to induce ototoxicity. Half an hour prior to cisplatin, groups 1, 2 and 3 received 2 ml of saline i.p., 6 mg/kg of riluzole hydrochloride i.p., and 8 mg/kg of riluzole hydrochloride i.p., respectively, for 3 days. The auditory brainstem responses were repeated 24 hours after the last drug administration. The cochleae were analyzed by transmission electron microscopy (TEM). Results After drug administiration, for 8,000 Hz stimulus, group 1 had significantly higher threshold shifts when compared with groups 2 (p < 0.05) and 3 (p < 0.05), and there was no significant difference in threshold shifts between groups 2 and 3 (p > 0.05). Transmission electron microscopy findings demonstrated the protective effect of riluzole on the hair cells and the stria vascularis, especially in the group treated with 8 mg/kg of riluzole hydrochloride. Conclusion We can say that riluzolemay have a protective effect on cisplatin- induced ototoxicity. However, additional studies are needed to confirm these results and the mechanisms of action of riluzole.

Relationship between serum ferritin level and amikacin ototoxicity

Aminoglycosides are highly effective against bacteria but have serious side-effects including ototoxicity and nephrotoxicity. One of the theories in aminoglycosides ototoxicity is that Ironaminoglycoside complex causes ototoxicity by creating free radicals. Based on this theory, the relationship between serum iron level and amikacin ototoxicity was studied to determine whether more iron results in more ototoxcity. This prospective cohort study was conducted from August 2005 to October 2008. Patients with amikacin prescription and different serum-ferritin levels were examined. Burned patients with amikacin prescription were divided into Group1 [89 patients; serum-ferritin >150] and Group2 [92 patients, serum-ferritin <150]. Their hearing thresholds and red-blood-cells indices were compared using t- and paired t-test. In comparing the two groups, thresholds of Group1 were higher than Group2 at all frequencies, and the difference was statistically significant [p<0.001]. The maximum threshold shift in Group1 was greater than 20 dB and in Group2, it was less than 10 dB, at 8000Hz. Again, this result was statistically and clinically significant [p<0.001]. Finally, the mean corpuscular volume [MCV] was higher in Group1 than Group2, and [p=0.001]. The results suggest that the level of iron is related to aminoglycoside ototoxicity. More iron can create more ototoxicity, and iron deficiency may inhibit aminoglycoside ototoxicity. An increase in MCV may be due to higher serum ferritin and an indication of more ototoxicity

Mutação mitocondrial C1494T, deficiência auditiva e uso de antibióticos aminoglicosídeos / C1494T mitochondrial dna mutation, hearing loss, and aminoglycosides antibiotics

Tendo em vista a complexidade do mecanismo da audição, não é difícil compreender que a deficiência auditiva possa resultar de ampla variedade de anomalias geneticamente determinadas, bem como de diversos fatores ambientais. Mutações específicas no gene 12S rRNA em DNA mitocondrial são responsáveis por perda da audição não-sindrômica de herança materna, e pelo aumento da susceptibilidade ototóxica dos antibióticos aminoglicosídeos. Objetivo: Neste trabalho, nós avaliamos a presença da mutação C1494T entre os indivíduos ouvintes e com deficiência auditiva que utilizaram aminoglicosídeos e os que não tiveram contato com o antibiótico. Material e método: Foram estudados 20 pacientes com deficiência auditiva neurossensorial não-sindrômica sem histórico de sensibilização aos aminoglicosídeos e 40 recém-nascidos, prematuros e de alto-risco que utilizaram a droga ototóxica, dos quais 20 eram ouvintes e 20 com perda auditiva. As amostras foram analisadas por PCR-RFLP com a enzima de restrição Hph I. Forma de estudo: Experimental. Resultados: A mutação mitocondrial C1494T no gene 12S rRNA não foi detectada em nenhuma das amostras analisadas. Conclusão: Nossos dados sugerem que a deficiência auditiva dos indivíduos analisados não está relacionada com a ototoxicidade da mutação C1494T, demonstrando que esta mutação não é frequente em nossa população.

In view of the complex mechanism of hearing, it is not difficult to understand that hearing impairment may result from a wide variety of genetically determined anomalies and various environmental factors. Specific mutations in the mitochondrial DNA 12S rRNA gene are responsible for maternally inherited non-syndromic hearing loss, and for increased susceptibility to the ototoxicity of aminoglycoside antibiotics. AIM: To asses the presence of C1494T mutation among individuals with normal hearing and hearing impairment who used aminoglycosides and those who had not had contact with the antibiotic. Material and method: The study was composed of 20 patients with nonsyndromic sensorineural hearing loss without prior use of aminoglycosides and 40 premature and high-risk newborns who used ototoxic drugs, of whom 20 had good hearing and 20 had hearing loss. The samples were analyzed by PCR-RFLP with the restriction enzyme Hph I. Study design: Experimental. Results: The mitochondrial 12S rRNA C1494T mutation was not detected in any of the samples analyzed. Conclusion: Our data suggest that the hearing loss of the individuals we analyzed was not related to the ototoxicity of mutation C1494T, showing that this mutation is not frequent in our population.

Estudo da ototoxicidade em trabalhadores expostos a organofosforados / Ototoxicity study in workers exposed to organophosphate

A exposição ocupacional e ambiental aos agrotóxicos evidencia-se como um grave problema de Saúde Pública em nosso país. Entre os sintomas apresentados, a tonteira se destaca, em decorrência de uma provável ação tóxica. OBJETIVO: O objetivo do estudo é caracterizar os resultados do exame vestibular de trabalhadores rurais expostos ocupacionalmente e ambientalmente aos agrotóxicos organofosforados. MATERIAL E MÉTODO: Foi realizado um estudo de coorte com corte transversal em 18 trabalhadores rurais de Teresópolis, RJ. A faixa etária variou de 16 a 59 anos com uma média de 39,6 anos, sendo 5 trabalhadores do sexo masculino e 13 do sexo feminino. Foram utilizados três questionários com perguntas relacionadas à saúde geral e auditiva e perguntas específicas à tonteira e suas relações com o trabalho. Todos os trabalhadores passaram por uma avaliação clínica e realizaram os exames vectoeletronistagmografia e audiometria. RESULTADOS: Os resultados mostraram que 16 trabalhadores apresentaram alterações do equilíbrio corporal de tipo periférico irritativo e 7 trabalhadores apresentaram perdas auditivas do tipo neurossensorial, sugerindo que os agrotóxicos induzem alterações do sistema vestibular através de uma intoxicação lenta e silenciosa. CONCLUSÕES: O olhar clínico sobre esta população exposta a substâncias neuro-ototóxicas requer uma abordagem interdisciplinar, assegurando uma intervenção terapêutica e preventiva eficaz.

Occupational and environmental exposure to agricultural pesticides represent an important health care problem in our country. Among the symptoms presented, dizziness stands out, because of a probable toxic action. AIM: The goal of our study was to characterize vestibular test results from rural workers occupationally and environmentally exposed to organophosphates used in agricultural pesticides. MATERIALS AND METHODS: We carried out a cohort cross-sectional study with 18 rural workers from Teresópolis, RJ. Age ranged between 16 and 59 years, with a mean value of 39.6 years, 5 were males and 13 females. We used three questionnaires with questions associated with general and auditory health, and more specific questions about dizziness and its association with work. All workers underwent clinical evaluation, audiometry and vectoelectronystagmography. RESULTS: results showed that 16 workers had irritative peripheral body balance disorder and 7 workers had sensorineural hearing loss, thus suggesting that agricultural pesticides cause vestibular alterations through a slow and silent intoxication. CONCLUSIONS: medical care for this population exposed to neurotoxic substances require an interdisciplinary approach, to guarantee efficient preventive and therapeutic measures.

Rastreamento da mutação mitocondrial A1555G em pacientes com deficiência auditiva sensorioneural / Screening of the mitochondrial A1555G mutation in patients with sensorineural hearing loss

A mutação mitocondrial A1555G é a principal alteração associada à surdez ocasionada pelo uso de aminoglicosídeos. OBJETIVO: Investigar a prevalência da mutação A1555G em pacientes com deficiência auditiva sensorioneural com e sem uso de antibióticos aminoglicosídeos. MATERIAL E MÉTODO: Estudo em amostras de 27 pacientes com surdez, como casos, e em 100 neonatos, com audição normal, como grupo controle. O DNA foi extraído de leucócitos de amostras de sangue e "primers" específicos foram utilizados para amplificar o gene do citocromo b e a região que abrange a mutação A1555G do DNA mitocondrial, usando as técnicas da Reação em Cadeia da Polimerase e do Polimorfismo no Comprimento de Fragmentos de Restrição. DESENHO CIENTÍFICO: Estudo de casos em corte transversal. RESULTADOS: A região do gene do citocromo b foi amplificada, sendo confirmada a presença do DNA mitocondrial em todas as 127 amostras do estudo. A mutação A1555G não foi identificada nos 27 pacientes com deficiência auditiva e no grupo controle (100 neonatos). CONCLUSÕES: Os resultados são concordantes com estudos que relatam que a mutação A1555G não é prevalente nas Américas. Há interesse na determinação da real prevalência dessa mutação e na investigação de outras mutações que possam ocasionar deficiência auditiva associada ou não ao uso de aminoglicosídeos na população brasileira.

The A1555G mitochondrial mutation is the main alteration associated with aminoglycoside-induced deafness. AIM: to investigate the prevalence of the A1555G mutation in patients sensorineural hearing loss patients with and without aminoglycosides antibiotic use. MATERIAL AND METHOD: a study of 27 cases with deafness as the sample, and 100 neonates with normal hearing as the control group. DNA was extracted from blood leukocyte samples, and specific oligonucleotide primers were designed to amplify the cytochrome b gene and the region which encloses the A1555G mutation of the mitocondrial DNA using the polymerase chain reaction and restriction fragment length polymorphism. DESIGN: a cross-sectional case study. RESULTS: a region of the cytochrome b gene was amplified and the presence of the mtDNA was confirmed in all of the 127 cases. The A1555G mutation was not found in any of the 27 patients with hearing loss or the control group with 100 neonates. CONCLUSION: the results agree with studies stating that the A1555G mutation is not prevalent in the Americas. There is interest in establishing the real prevalence of this mutation and to investigate other mutations that may cause hearing loss, associated or not with the use of aminoglycosides, in the Brazilian population.

Audiological findings in individuals exposed to organic solvents: case studies.

Millions of people around the world are exposed to industrial organic solvents such as toluene and xylene in the manufacturing sectors. Solvents are neurotoxic substances that are detrimental to the functioning of the nervous system, including the central auditory nervous system (CANS). This study investigated hearing and auditory processing in seven individuals with a history of exposure to industrial solvents. A battery of audiological tests was administered to all subjects: pure tone, speech, and impedance audiometry, otoacoustic emissions tests, auditory brainstem responses, middle latency responses, as well as the SCAN-A and R-SPIN tests with low predictability sentence lists. All individuals in this study exhibited findings consistent with retrocochlear and/or central abnormality. Two of the seven subjects in this study had normal pure tone thresholds at all frequencies bilaterally, yet showed abnormal retrocochlear/central results on one or more tests. The auditory test battery approach used in this study appears to be valuable in evaluating the pathological conditions of the CANS in solvent-exposed individuals.

A woman with sudden bilateral sensorineural hearing loss after treatment psoriasis with acitretin.

A case of psoriasis presented with sudden simultaneous bilateral sudden sensorineural hearing loss after taking oral acitretin. Audiogram showed bilateral symmetrical sensorineural hearing loss. Her symptom improved after a short course of prednisolone. It is suggested that acitretin may affect hearing acuity.

Hipoacusia neurosensorial reversible por intoxicación con monóxido de carbono / Reversible neurosensorial hearing loss of intoxication with carbon monoxide

Se presenta el caso de una paciente de 35 años que sufrió una intoxicación crónica por monóxido de carbono (CO), con una sobreexposición final de tipo agudo, por lo cual requirió un tratamiento médico de urgencia y que desarrolló un compromiso otológico bilateral fundamentalmente neurosensorial, de tipo reversible y con compromiso principalmente de los tonos agudos. La intoxicación por CO, es una patología que rara vez se relaciona con alteraciones a nivel del oído. Las intoxicaciones agudas, que son las más frecuentemente diagnosticadas debido a lo evidente y dramático de su sintomatología, no presentan daño coclear presuntamente por el corto tiempo de exposición al CO. Distinto es el caso de la intoxicación de tipo crónica, en la cual la sintomatología es tan inespecífica y solapada que no se sospecha su presencia, unido a las características del gas el cual es inodoro, incoloro e insípido y no irritativo, por lo que ingresa en grandes cantidades al organismo por las vías respiratorias sin que la persona se percate de ello. Por este motivo generalmente es subdiagnosticada. Los estudios realizados en ratas, cobayos y las experiencias de intoxicaciones en humanos han demostrado que produce alteraciones cocleares reversibles

Regeneraçäo de Células após Ototoxicidade com Aminoglicosídeo na Cóclea de Aves / Hair Cell Regeneration in the Avian Cochlea after Ototoxicity with Aminoglycoside

Introduçäo: As células ciliadas podem ser lesada por inúmeros agentes, incluindo os antibióticos aminoglicosídeos. Na cóclea das aves, a perda das células ciliadas pode ser reposta por regeneraçäo. Objetivos: Os objetivos da pesquisa foram estudar o processo de regeneraçäo em aves e a progressäo temporal das lesöes provocadas pela gentamicina. Material e método: No estudo, foi administrada gentamicina em dose única subcutânea de 125 e 250 mg/kg respectivamente, em um e outro grupos de pintos de três dias. As cócleas foram processadas, para anáIise em microscopia eletrônica de varredura, no 1§, 3§, 5§ e 20§ dias após a injeçäo. A sequência celular de degeneraçäo e regeneraçäo foi estudada. No 20§ dia, a maior parte da área cóclear lesada havia sido reposta por células ciliadas e de suporte regeneradas. Estereocílios e microvilos foram observados na superfície apical das células ciliadas regeneradas

Ototoxicidade após o uso tópico de neomicina em pacientes com queimaduras / Ototoxicity after the topic use of neomycin in burned patients

Os utores relatam quatro casos de queimaduras extensas que, após utilizaçäo de creme de neomicina nas áreas cruentas, apresentaram ototoxicidade com graus variáveis de perda auditiva. Discutem o diagnóstico diferencial e alertam para o perigo da absorçäo de medicamentos usados por via tópica