RESUMEN
INTRODUCTION: Noise-induced hearing loss is one of the most common forms of sensorineural hearing loss. Nevertheless, the mechanisms of noise-induced hearing loss are still not fully understood. OBJECTIVE: To investigate the dynamics of inflammatory responses in the mammalian cochlea following noise trauma at two different times, once during the light cycle and once during the dark. METHODS: We challenged C57BL/6J mice with moderate, continuous noise trauma at either 9 a.m. or 9 p.m. Auditory function, histological changes in hair cells, and modifications in gene expression levels of inflammatory mediators were assessed at specific time points. Shifts in auditory brainstem response thresholds were measured at 1, 3, 7 and 14 days after noise exposure to measure potential noise-induced hearing loss. Cochlear basilar-membrane immunofluorescent staining was performed at 3 and 14 days after noise exposure. The mRNA levels of several inflammatory mediators were measured via quantitative real-time polymerase chain reaction before (pre) and after (0, 3, 12, 24 and 72â¯h) noise exposure. RESULTS: We found that all noise-exposed mice developed a temporary threshold shift and that there were no significant differences between daytime and nighttime noise exposures in terms of inducing hearing-threshold shifts. Similarly, we did not detect significant histological changes in hair cells between these two groups. However, we discovered an interesting phenomenon in that the peak mRNA levels of IL-1ß, IL-6, CCL2 and TNF-α were higher in day noise-exposed mice compared to those in night noise-exposed mice, and these mRNA levels subsided more slowly in day noise-exposed mice. CONCLUSION: Overall, these observations suggest that the circadian timing of noise exposure has a significant effect on noise-induced inflammatory responses in the mouse cochlea and that a greater inflammatory response might occur after daytime exposure.
Asunto(s)
Pérdida Auditiva Provocada por Ruido , Ratones , Animales , Umbral Auditivo/fisiología , Potenciales Evocados Auditivos del Tronco Encefálico/fisiología , Ratones Endogámicos C57BL , Cóclea/patología , Mediadores de Inflamación/metabolismo , ARN Mensajero/metabolismo , MamíferosRESUMEN
In animal models, prolonged exposure (2 h) to high-level noise causes an irreparable damage to the synapses between the inner hair cells and auditory nerve fibers within the cochlea. Nevertheless, this injury does not necessarily alter the hearing threshold. Similar findings have been observed as part of typical aging in animals. This type of cochlear synaptopathy, popularly called "hidden hearing loss," has been a significant issue in neuroscience research and clinical audiology scientists. The results obtained in different investigations are inconclusive in their diagnosis and suggest new strategies for both prognosis and treatment of cochlear synaptopathy. Here we review the major physiological findings regarding cochlear synaptopathy in animals and humans and discuss mathematical models. We also analyze the potential impact of these results on clinical practice and therapeutic options.
Asunto(s)
Cóclea/patología , Audición/fisiología , Ruido/efectos adversos , Sinapsis/fisiología , Transmisión Sináptica/fisiología , Animales , Modelos Animales de Enfermedad , HumanosRESUMEN
Abstract Introduction Ototoxicity is a health problem appearing after powerful treatments in serious health conditions. It is sometimes inevitable when treatment of the serious disease is required. Cisplatin is an antineoplastic agent which was investigated previously to reveal increased nitrogen and reactive oxygen radicals that damages hair cells, resulting in ototoxicity. N-acetylcysteine, previously shown to decrease ototoxicity caused by different agents, is known to be a powerful in vitro antioxidant. Probably N-acetylcysteine, in addition to its antioxidant effect, blocks a cascade where reactive oxygen species result in apoptosis in the cochlea. Objectives The possible preventive effect of N-acetylcysteine in cisplatin ototoxicity was studied with auditory brain stem responses, otoacoustic emissions, and histopathological investigation of the cochlea in a scanning electron microscopy. Methods This study was conducted on 21 Wistar Albino rats in four groups. 1 mL/kg/day three times in total intraperitoneal (i.p.) Saline (n = 5), 500 mg/kg/day i.p. three times in total N-acetylcysteine (n = 5), i.p. 15 mg/kg cisplatin alone (single dose) (n = 5) and i.p. 15 mg/kg cisplatin plus 500 mg/kg/day N-acetylcysteine (n = 6) were administered. The rats were anesthetized to study the hearing tests before and after the experiment. The rats were sacrificed to investigate the cochleas by scanning electron microscopy. Results Auditory brain stem responses and otoacoustic emissions values were attenuated in the cisplatin group. The group that received N-acetylcysteine in addition to cisplatin had better auditory brain stem responses thresholds and otoacoustic emissions. The samples obtained from the cisplatin group showed surface irregularities, degeneration areas, and total or partial severe stereocilia losses. The changes were milder in the cisplatin + N-acetylcysteine group. Conclusion Cisplatin ototoxicity can be detected by auditory brain stem responses and otoacoustic emissions testing in rats. N-acetylcysteine may protect the cochlear cells from histopathological changes. We concluded that N-acetylcysteine given 4 h after cisplatin injection has a potential otoprotective effect against cisplatin ototoxicity. which suggests it could be used in clinical trials.
Resumo Introdução A ototoxicidade é um problema que pode ocorrer após certos tipos de tratamentos para condições graves de saúde. Às vezes é inevitável quando o tratamento da doença é necessário. A cisplatina é um agente antineoplásico cujo uso em pesquisas anteriores demonstrou aumentar os radicais livres de nitrogênio e espécies reativas de oxigênio que danificam as células ciliadas e resultam em ototoxicidade. Por outro lado, a N-acetilcisteína, que já demonstrou diminuir a ototoxicidade causada por diferentes agentes, é conhecida por ser um potente antioxidante in vitro. Provavelmente a N-acetilcisteína, além de seu efeito antioxidante, bloqueia uma cascata onde espécies reativas de oxigênio resultam em apoptose na cóclea. Objetivos Estudar o possível efeito preventivo da N-acetilcisteína na ototoxicidade por cisplatina por meio de potencial evocado auditivo de tronco encefálico, emissões otoacústicas e investigação histopatológica da cóclea por microscopia eletrônica de varredura. Método Este estudo foi realizado em 21 ratos albinos Wistar, separados em quatro grupos. Foram administrados: 1 mL/kg/dia intraperitoneal (i.p.) de solução salina (n = 5), três vezes no total; 500 mg/kg/dia i.p. de N-acetilcisteína (n = 5), três vezes no total; 15 mg/kg i.p. (dose única) somente de cisplatina (n = 5) e 15 mg/kg i.p. de cisplatina e 500 mg/kg/dia i.p. de N-acetilcisteína (n = 6). Os ratos foram anestesiados para estudo dos testes auditivos antes e depois do experimento. Os ratos foram sacrificados para investigação da cóclea por microscopia eletrônica de varredura. Resultados Os potenciais evocados auditivos de tronco encefálico e os valores das emissões otoacústicas estavam atenuados no grupo cisplatina. O grupo que recebeu N-acetilcisteína além da cisplatina apresentou melhores limiares de respostas auditivas do tronco encefálico e emissões otoacústicas. As amostras obtidas do grupo cisplatina apresentaram irregularidades de superfície, áreas de degeneração, com perdas graves totais ou parciais de estereocílios. As alterações foram mais leves no grupo cisplatina + N-acetilcisteína. Conclusão A ototoxicidade por cisplatina pode ser detectada por meio de potenciais evocados auditivos de tronco encefálico e pelo teste de emissões otoacústicas em ratos. A N-acetilcisteína pode proteger as células cocleares contra alterações histopatológicas. Concluímos que a N-acetilcisteína administrada 4 horas após a injeção de cisplatina tem potencial efeito otoprotetor contra a ototoxicidade por cisplatina e pode ser utilizada em ensaios clínicos.
Asunto(s)
Animales , Masculino , Acetilcisteína/administración & dosificación , Cisplatino/efectos adversos , Sustancias Protectoras/administración & dosificación , Ototoxicidad/etiología , Antineoplásicos/efectos adversos , Antioxidantes/administración & dosificación , Acetilcisteína/farmacología , Microscopía Electrónica de Rastreo , Potenciales Evocados Auditivos del Tronco Encefálico , Ratas Wistar , Cóclea/patología , Apoptosis , Células Ciliadas Auditivas Externas/efectos de los fármacos , Células Ciliadas Auditivas Externas/patología , Sustancias Protectoras/farmacología , Modelos Animales de Enfermedad , Estereocilios/efectos de los fármacos , Estereocilios/patología , Ototoxicidad/prevención & control , Pruebas Auditivas , Antioxidantes/farmacologíaRESUMEN
INTRODUCTION: Ototoxicity is a health problem appearing after powerful treatments in serious health conditions. It is sometimes inevitable when treatment of the serious disease is required. Cisplatin is an antineoplastic agent which was investigated previously to reveal increased nitrogen and reactive oxygen radicals that damages hair cells, resulting in ototoxicity. N-acetylcysteine, previously shown to decrease ototoxicity caused by different agents, is known to be a powerful in vitro antioxidant. Probably N-acetylcysteine, in addition to its antioxidant effect, blocks a cascade where reactive oxygen species result in apoptosis in the cochlea. OBJECTIVES: The possible preventive effect of N-acetylcysteine in cisplatin ototoxicity was studied with auditory brain stem responses, otoacoustic emissions, and histopathological investigation of the cochlea in a scanning electron microscopy. METHODS: This study was conducted on 21 Wistar Albino rats in four groups. 1mL/kg/day three times in total intraperitoneal (i.p.) Saline (n=5), 500mg/kg/day i.p. three times in total N-acetylcysteine (n=5), i.p. 15mg/kg cisplatin alone (single dose) (n=5) and i.p. 15mg/kg cisplatin plus 500mg/kg/day N-acetylcysteine (n=6) were administered. The rats were anesthetized to study the hearing tests before and after the experiment. The rats were sacrificed to investigate the cochleas by scanning electron microscopy. RESULTS: Auditory brain stem responses and otoacoustic emissions values were attenuated in the cisplatin group. The group that received N-acetylcysteine in addition to cisplatin had better auditory brain stem responses thresholds and otoacoustic emissions. The samples obtained from the cisplatin group showed surface irregularities, degeneration areas, and total or partial severe stereocilia losses. The changes were milder in the cisplatin+N-acetylcysteine group. CONCLUSION: Cisplatin ototoxicity can be detected by auditory brain stem responses and otoacoustic emissions testing in rats. N-acetylcysteine may protect the cochlear cells from histopathological changes. We concluded that N-acetylcysteine given 4h after cisplatin injection has a potential otoprotective effect against cisplatin ototoxicity. which suggests it could be used in clinical trials.
Asunto(s)
Acetilcisteína/administración & dosificación , Antineoplásicos/efectos adversos , Antioxidantes/administración & dosificación , Cisplatino/efectos adversos , Ototoxicidad/etiología , Sustancias Protectoras/administración & dosificación , Acetilcisteína/farmacología , Animales , Antioxidantes/farmacología , Apoptosis , Cóclea/efectos de los fármacos , Cóclea/patología , Modelos Animales de Enfermedad , Potenciales Evocados Auditivos del Tronco Encefálico , Células Ciliadas Auditivas Externas/efectos de los fármacos , Células Ciliadas Auditivas Externas/patología , Pruebas Auditivas , Masculino , Microscopía Electrónica de Rastreo , Ototoxicidad/prevención & control , Sustancias Protectoras/farmacología , Ratas Wistar , Relación Señal-Ruido , Estereocilios/efectos de los fármacos , Estereocilios/patologíaRESUMEN
Abstract Introduction: Ototoxicity refers to cellular damage or function impairment developing in the inner ear in association with any therapeutic agent or chemical substance, and still represents the principal side-effect restricting the use of cisplatin. Objective: The aim of this study was to perform a biochemical, functional and histopathological investigation of the potential protective effect of eugenol against cisplatin-induced ototoxicity. Methods: The study was performed with 24 female Sprague Dawley rats. Distortion product otoacoustic emissions tests were performed on all animals, which were randomized into four equal groups. A single intraperitoneal dose of 15 mg/kg cisplatin was administered to cisplatin group, while the eugenol group received 100 mg/kg eugenol intraperitoneal for five consecutive days. 100 mg/kg eugenol was administered to cisplatin + eugenol group for 5 days. On the third day, these rats were received a single dose of 15 mg/kg cisplatin. The control group was given 8 mL/kg/day intraperitoneal saline solution for five days. The distortion product otoacoustic emissions test was repeated 24 h after the final drug administration. All animals were sacrificed, and the cochleas were subsequently used for biochemical and histopathological examinations. Results: Cisplatin caused oxidative stress in the cochlea, impaired the cochlear structure and significantly reduced signal noise ratio levels. Administration of eugenol together with cisplatin reversed these effects and provided functional, biochemical and histopathological protection. Conclusion: The study findings represent the first indication in the literature that eugenol may protect against ototoxicity by raising levels of antioxidant enzymes and lowering those of oxidant parameters.
Resumo Introdução: A ototoxicidade refere-se ao dano celular ou comprometimento da função da orelha interna associado a qualquer agente terapêutico ou substância química e ainda representa o principal efeito colateral que restringe o uso da cisplatina. Objetivo: O objetivo deste estudo foi realizar uma investigação bioquímica, funcional e histopatológica do potencial efeito protetor do eugenol contra a ototoxicidade induzida pela cisplatina. Método: O estudo foi realizado com 24 ratos fêmeas Sprague Dawley. Testes de emissões otoacústicas por produto de distorção foram realizados em todos os animais, os quais foram randomizados em quatro grupos iguais. Uma única dose intraperitoneal de 15 mg/kg de cisplatina foi administrada ao grupo cisplatina, enquanto o grupo eugenol recebeu 100 mg/kg de eugenol intraperitoneal por cinco dias consecutivos. Foram administrados 100 mg/kg de eugenol ao grupo cisplatina + eugenol durante 5 dias. No terceiro dia, estes ratos receberam uma dose única de 15 mg/kg de cisplatina. O grupo controle recebeu 8 mL/kg/dia de solução salina intraperitoneal por cinco dias. O teste de emissões otoacústicas por produto de distorção foi repetido 24 horas após a administração final do medicamento. Todos os animais foram sacrificados e as cócleas foram posteriormente utilizadas para exames bioquímicos e histopatológicos. Resultados: A cisplatina causou estresse oxidativo na cóclea, prejudicou a estrutura coclear e reduziu significativamente os níveis da relação sinal/ruído. A administração de eugenol juntamente com a cisplatina reverteu esses efeitos e forneceu proteção funcional, bioquímica e histopatológica. Conclusão: Os achados do estudo representam a primeira indicação na literatura de que o eugenol pode proteger contra a ototoxicidade, eleva os níveis de enzimas antioxidantes e diminui os níveis dos parâmetros oxidantes.
Asunto(s)
Animales , Femenino , Ratas , Eugenol/uso terapéutico , Cisplatino/toxicidad , Pérdida Auditiva/prevención & control , Antineoplásicos/toxicidad , Antioxidantes/uso terapéutico , Ratas Sprague-Dawley , Emisiones Otoacústicas Espontáneas/efectos de los fármacos , Cóclea/efectos de los fármacos , Cóclea/patología , Modelos Animales de Enfermedad , Pérdida Auditiva/inducido químicamenteRESUMEN
Abstract Introduction: Cisplatin is an antineoplastic agent widely used in the treatment of a variety of cancers. Ototoxicity is one of the main side-effects restricting the use of cisplatin. Objective: The purpose of this study was to investigate the protective efficacy of gallic acid, in biochemical, functional and histopathological terms, against ototoxicity induced by cisplatin. Methods: Twenty-eight female Sprague Dawley rats were included. Rats were randomly assigned into four groups of seven animals each. Cisplatin group received a single intraperitoneal dose of 15 mg/kg cisplatin. Gallic acid group received intraperitoneal gallic acid at 100 mg/kg for five consecutive days. Cisplatin + gallic acid group received intraperitoneal gallic acid at 100 mg/kg for five consecutive days and a single intraperitoneal dose of 15 mg/kg cisplatin at 3rd day. A control group received 1 mL intraperitoneal saline solution for five consecutive days. Prior to drug administration, all rats were exposed to the distortion product otoacoustic emissions test. The test was repeated on the 6th day of the study. All rats were then sacrificed; the cochleas were removed and set aside for biochemical and histopathological analyses. Results: In cisplatin group, Day 6 signal noise ratio values were significantly lower than those of the other groups. Also, malondialdehyde levels in cochlear tissues were significantly higher, superoxide dismutase and glutathione peroxidase activities were significantly lower compared to the control group. Histopathologic evaluation revealed erosion in the stria vascularis, degeneration and edema in the connective tissue layer in endothelial cells, impairment of outer hair cells and a decrease in the number of these calls. In the cisplatin + gallic acid group, this biochemical, histopathological and functional changes were reversed. Conclusion: In the light of our findings, we think that gallic acid may have played a protective role against cisplatin-induced ototoxicity in rats, as indicated by the distortion product otoacoustic emissions test results, biochemical findings and immunohistochemical analyses.
Resumo Introdução: A cisplatina é um agente antineoplásico amplamente usado no tratamento de vários tipos de câncer. A ototoxicidade é um dos principais efeitos colaterais que restringem o uso da cisplatina. Objetivo: O objetivo deste estudo foi investigar a eficácia protetora do ácido gálico, em termos bioquímicos, funcionais e histopatológicos, contra a ototoxicidade induzida por cisplatina. Método: Vinte e oito ratas Sprague-Dawley foram incluídas. As ratas foram distribuídas aleatoriamente em quatro grupos de sete animais cada. O grupo cisplatina recebeu uma única dose intraperitoneal de 15 mg/kg de cisplatina. O grupo ácido gálico recebeu ácido gálico via intraperitoneal a uma dose de 100 mg/kg durante cinco dias consecutivos. O grupo cisplatina + ácido gálico recebeu ácido gálico via intraperitoneal a uma dose de 100 mg/kg durante cinco dias consecutivos e uma única dose intraperitoneal de 15 mg/kg de cisplatina no terceiro dia. O grupo controle recebeu 1 mL de solução salina via intraperitoneal por cinco dias consecutivos. Antes da administração do fármaco, todos os ratos foram expostos ao teste de emissões otoacústicas - produto de distorção. O teste foi repetido no sexto dia do estudo. Todos os ratos foram então sacrificados; as cócleas foram removidas e reservadas para análises bioquímicas e histopatológicas. Resultados: No grupo cisplatina, os valores da relação sinal-ruído do dia 6 foram significativamente mais baixos aos dos outros grupos. Além disso, os níveis de malondialdeído nos tecidos cocleares foram significativamente mais altos, e as atividades de superóxido dismutase e glutatione peroxidase foram significativamente mais baixas em comparação com o grupo controle. A avaliação histopatológica revelou erosão na estria vascular, degeneração e edema na camada de tecido conjuntivo em células endoteliais, comprometimento das células ciliadas externas e diminuição do número dessas células. No grupo cisplatina + ácido gálico, estas alterações bioquímicas, histopatológicas e funcionais foram revertidas. Conclusão: Tendo em vista os nossos achados, consideramos que o ácido gálico pode ter desempenhado um papel protetor contra a ototoxicidade induzida por cisplatina em ratas, conforme indicado pelos resultados do teste emissões otoacústicas - produto de distorção, achados bioquímicos e análises imuno-histoquímicas.
Asunto(s)
Animales , Femenino , Ratas , Cisplatino/toxicidad , Emisiones Otoacústicas Espontáneas/efectos de los fármacos , Cóclea/efectos de los fármacos , Cóclea/patología , Sustancias Protectoras/administración & dosificación , Ácido Gálico/administración & dosificación , Estimulación Acústica , Inmunohistoquímica , Ratas Sprague-Dawley , Modelos Animales de Enfermedad , Inyecciones IntraperitonealesRESUMEN
Abstract Introduction: In daily life biological systems are usually exposed to magnetic field forces at different intensities and frequencies, either directly or indirectly. Despite negative results, the therapeutic use of the low dose magnetic field has been found in recent studies. The effect of magnetic field forces on cochlear cells is not clear in the literature. Objective: In our study, we first applied in vivo pulsed magnetic fields to laboratory rats to investigate the effects on cochlea with distortion product otoacoustic emission test followed by histopathological examinations. Methods: Twelve rats were included in this study, separated into two groups as study group and control group. The rats in the study group were exposed to 40 Hz pulsed magnetic field for 1 h/day for 30 days; the hearing of the rats was controlled by otoacoustic emission test. Also, their cochleas were removed and histochemical examination was performed by Caspase-3, Caspase-9, and TUNEL methods. Results: A statistically significant difference was determined (p < 0.05) when the hearing thresholds of the groups obtained by using 5714 Hz and 8000 Hz stimuli were compared by Kruskal-Wallis test. A significant reaction was observed in the study group, especially in the outer ciliated cells during immunohistochemical examinations by using Caspase-3 and Caspase-9 methods. A significantly positive difference was determined in the study group, especially at the outer ciliated cells and the support cells of the corti organ, when compared to the control group (p < 0.05) by the TUNEL method. Conclusion: According to the results of our study, the very low dose magnetic field, which is considered to be used for therapeutic purposes recently, can cause both auditory function defects and histopathologic damage in cochlear cells.
Resumo Introdução: Os sistemas biológicos são geralmente expostos a forças de campo magnético em diferentes intensidades e frequências, direta ou indiretamente, na vida diária. Apesar dos resultados negativos, o uso terapêutico do campo magnético de baixa dose tem sido encontrado em estudos recentes. O efeito das forças do campo magnético sobre as células cocleares não está claro na literatura. Objetivo: Em nosso estudo, aplicamos pela primeira vez campos magnéticos pulsados in vivo em ratos de laboratório para investigar os efeitos na cóclea através do teste de emissão otoacústica por produto de distorção e análises histopatológicas. Método: Doze ratos foram incluídos neste estudo, os quais foram separados em dois grupos, grupo de estudo e grupo controle. Os ratos do grupo de estudo foram expostos a campo magnético pulsado de 40 Hz por 1 hora/dia por 30 dias, e a audição dos ratos foi controlada por testes de emissão otoacústica. Além disso, suas cócleas foram colhidas e o exame histoquímico foi feito pelos métodos caspase-3, caspase-9 e TUNEL. Resultados: Foi determinada uma diferença estatisticamente significante (p < 0,05) quando os limiares auditivos dos grupos obtidos por meio dos estímulos de 5714 Hz e 8000 Hz foram comparados pelo teste de Kruskal-Wallis. Uma reação significante foi observada no grupo de estudo, especialmente nas células ciliadas externas nas análises imuno-histoquímicas, com os métodos caspase-3 e caspase-9. Uma diferença significantemente positiva foi determinada no grupo de estudo, especialmente nas células ciliadas externas e nas células de suporte do órgão de Corti, quando comparadas com o grupo controle (p < 0,05) pelo método TUNEL. Conclusão: De acordo com os resultados do nosso estudo, o campo magnético de dose baixa, que tem sido considerado para uso terapêutico recentemente, pode causar defeitos na função auditiva e danos histopatológicos nas células cocleares.
Asunto(s)
Animales , Masculino , Ratas , Cóclea/patología , Células Ciliadas Auditivas Externas/patología , Campos Electromagnéticos/efectos adversos , Inmunohistoquímica , Ratas Wistar , Emisiones Otoacústicas Espontáneas , Estadísticas no ParamétricasRESUMEN
Abstract Introduction: Cisplatin is one of the main chemotherapeutic agents used for the treatment of many types of cancer. However, ototoxicity, one of the most serious side effects of cisplatin, restricts its usage. Objective: We aimed to investigate the protective effects of whortleberry extract against cisplatin-induced ototoxicity by evaluating hearing and histopathological cochlear damage and by measuring the biochemical parameters affected byoxidative stress. Methods: Forty-eight male rats were included in the study after performing Distortion Product Otoacoustic Emission test to confirm that their hearing levels were normal. The rats were randomly divided into six groups: the control group, the sham group, and, which received only whortleberry extract, only cisplatin, cisplatin + 100 mg whortleberry extract, cisplatin + 200 mg whortleberry extract, respectively. Audiologic investigation was performed by performing the Distortion Product Otoacoustic Emission test at the beginning and at the eighth day of the study. Cardiac blood samples were collected for biochemical analysis, and the rats were sacrificed to obtain cochlear histopathological specimens on the eighth day. Results: The results revealed that whortleberry protects hearing against cisplatin-induced ototoxicity independent of the dose. However, high doses of whortleberry extract are needed to prevent histopathological degeneration and oxidative stress. Conclusion: The results obtained in this study show that whortleberry extract has a protective effect against cisplatin-induced ototoxicity.
Resumo Introdução: A cisplatina é um dos principais agentes quimioterápicos utilizados para o tratamento de muitos tipos de câncer. No entanto, a ototoxicidade, um dos efeitos colaterais mais graves da cisplatina, restringe seu uso. Objetivo: Nosso objetivo foi investigar os efeitos protetores do extrato de uva-do-monte contra a ototoxicidade induzida por cisplatina, avaliar o dano auditivo e histopatológico coclear e medir os parâmetros bioquímicos afetados pelo estresse oxidativo. Método: Foram incluídos no estudo 48 ratos machos após teste de emissão otoacústica evocada por produto de distorção para confirmar que seus níveis de audição eram normais. Os ratos foram divididos aleatoriamente em seis grupos: o grupo controle, o grupo simulado, o que recebeu apenas extrato de uva-do-monte, o que recebeu apenas cisplatina, o que recebeu cisplatina + 100 mg de extrato de uva-do-monte e o que recebeu cisplatina + 200 mg de extrato de uva-do-monte, respectivamente. A investigação audiológica foi feita através do teste de emissão otoacústica de produto de distorção no início e no oitavo dia do estudo. As amostras de sangue cardíaco foram coletadas para análise bioquímica e os ratos foram sacrificados para obtenção de espécimes histopatológicos cocleares no oitavo dia. Resultados: Os resultados revelaram que o extrato de uva-do-monte protege a audição contra a ototoxicidade induzida por cisplatina, independentemente da dose. No entanto, são necessárias doses elevadas do extrato para evitar a degeneração histopatológica e o estresse oxidativo. Conclusão: Os resultados obtidos neste estudo mostram que o extrato de uva-do-monte tem um efeito protetor contra a ototoxicidade induzida por cisplatina.
Asunto(s)
Animales , Masculino , Cisplatino/toxicidad , Cóclea/efectos de los fármacos , Sustancias Protectoras/uso terapéutico , Audición/efectos de los fármacos , Antocianinas/uso terapéutico , Antineoplásicos/toxicidad , Valores de Referencia , Estimulación Acústica , Distribución Aleatoria , Reproducibilidad de los Resultados , Resultado del Tratamiento , Ratas Wistar , Emisiones Otoacústicas Espontáneas/efectos de los fármacos , Cóclea/patología , Estrés Oxidativo/efectos de los fármacos , Antioxidantes/uso terapéuticoRESUMEN
INTRODUCTION: Cisplatin is one of the main chemotherapeutic agents used for the treatment of many types of cancer. However, ototoxicity, one of the most serious side effects of cisplatin, restricts its usage. OBJECTIVE: We aimed to investigate the protective effects of whortleberry extract against cisplatin-induced ototoxicity by evaluating hearing and histopathological cochlear damage and by measuring the biochemical parameters affected byoxidative stress. METHODS: Forty-eight male rats were included in the study after performing Distortion Product Otoacoustic Emission test to confirm that their hearing levels were normal. The rats were randomly divided into six groups: the control group, the sham group, and, which received only whortleberry extract, only cisplatin, cisplatin+100mg whortleberry extract, cisplatin+200mg whortleberry extract, respectively. Audiologic investigation was performed by performing the Distortion Product Otoacoustic Emission test at the beginning and at the eighth day of the study. Cardiac blood samples were collected for biochemical analysis, and the rats were sacrificed to obtain cochlear histopathological specimens on the eighth day. RESULTS: The results revealed that whortleberry protects hearing against cisplatin-induced ototoxicity independent of the dose. However, high doses of whortleberry extract are needed to prevent histopathological degeneration and oxidative stress. CONCLUSION: The results obtained in this study show that whortleberry extract has a protective effect against cisplatin-induced ototoxicity.
Asunto(s)
Antocianinas/uso terapéutico , Antineoplásicos/toxicidad , Cisplatino/toxicidad , Cóclea/efectos de los fármacos , Audición/efectos de los fármacos , Sustancias Protectoras/uso terapéutico , Estimulación Acústica , Animales , Antioxidantes/uso terapéutico , Cóclea/patología , Masculino , Emisiones Otoacústicas Espontáneas/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales , Distribución Aleatoria , Ratas Wistar , Valores de Referencia , Reproducibilidad de los Resultados , Relación Señal-Ruido , Resultado del Tratamiento , Vaccinium myrtillusRESUMEN
INTRODUCTION: Cisplatin is an antineoplastic agent widely used in the treatment of a variety of cancers. Ototoxicity is one of the main side-effects restricting the use of cisplatin. OBJECTIVE: The purpose of this study was to investigate the protective efficacy of gallic acid, in biochemical, functional and histopathological terms, against ototoxicity induced by cisplatin. METHODS: Twenty-eight female Sprague Dawley rats were included. Rats were randomly assigned into four groups of seven animals each. Cisplatin group received a single intraperitoneal dose of 15mg/kg cisplatin. Gallic acid group received intraperitoneal gallic acid at 100mg/kg for five consecutive days. Cisplatin+gallic acid group received intraperitoneal gallic acid at 100mg/kg for five consecutive days and a single intraperitoneal dose of 15mg/kg cisplatin at 3rd day. A control group received 1mL intraperitoneal saline solution for five consecutive days. Prior to drug administration, all rats were exposed to the distortion product otoacoustic emissions test. The test was repeated on the 6th day of the study. All rats were then sacrificed; the cochleas were removed and set aside for biochemical and histopathological analyses. RESULTS: In cisplatin group, Day 6 signal noise ratio values were significantly lower than those of the other groups. Also, malondialdehyde levels in cochlear tissues were significantly higher, superoxide dismutase and glutathione peroxidase activities were significantly lower compared to the control group. Histopathologic evaluation revealed erosion in the stria vascularis, degeneration and edema in the connective tissue layer in endothelial cells, impairment of outer hair cells and a decrease in the number of these calls. In the cisplatin+gallic acid group, this biochemical, histopathological and functional changes were reversed. CONCLUSION: In the light of our findings, we think that gallic acid may have played a protective role against cisplatin-induced ototoxicity in rats, as indicated by the distortion product otoacoustic emissions test results, biochemical findings and immunohistochemical analyses.
Asunto(s)
Cisplatino/toxicidad , Cóclea/efectos de los fármacos , Cóclea/patología , Ácido Gálico/administración & dosificación , Emisiones Otoacústicas Espontáneas/efectos de los fármacos , Sustancias Protectoras/administración & dosificación , Estimulación Acústica , Animales , Modelos Animales de Enfermedad , Femenino , Inmunohistoquímica , Inyecciones Intraperitoneales , Ratas , Ratas Sprague-DawleyRESUMEN
INTRODUCTION: Ototoxicity refers to cellular damage or function impairment developing in the inner ear in association with any therapeutic agent or chemical substance, and still represents the principal side-effect restricting the use of cisplatin. OBJECTIVE: The aim of this study was to perform a biochemical, functional and histopathological investigation of the potential protective effect of eugenol against cisplatin-induced ototoxicity. METHODS: The study was performed with 24 female Sprague Dawley rats. Distortion product otoacoustic emissions tests were performed on all animals, which were randomized into four equal groups. A single intraperitoneal dose of 15mg/kg cisplatin was administered to cisplatin group, while the eugenol group received 100mg/kg eugenol intraperitoneal for five consecutive days. 100mg/kg eugenol was administered to cisplatin+eugenol group for 5 days. On the third day, these rats were received a single dose of 15mg/kg cisplatin. The control group was given 8mL/kg/day intraperitoneal saline solution for five days. The distortion product otoacoustic emissions test was repeated 24h after the final drug administration. All animals were sacrificed, and the cochleas were subsequently used for biochemical and histopathological examinations. RESULTS: Cisplatin caused oxidative stress in the cochlea, impaired the cochlear structure and significantly reduced signal noise ratio levels. Administration of eugenol together with cisplatin reversed these effects and provided functional, biochemical and histopathological protection. CONCLUSION: The study findings represent the first indication in the literature that eugenol may protect against ototoxicity by raising levels of antioxidant enzymes and lowering those of oxidant parameters.
Asunto(s)
Antineoplásicos/toxicidad , Antioxidantes/uso terapéutico , Cisplatino/toxicidad , Eugenol/uso terapéutico , Pérdida Auditiva/prevención & control , Animales , Cóclea/efectos de los fármacos , Cóclea/patología , Modelos Animales de Enfermedad , Femenino , Pérdida Auditiva/inducido químicamente , Emisiones Otoacústicas Espontáneas/efectos de los fármacos , Ratas , Ratas Sprague-DawleyRESUMEN
In mammals, the cochlear sensory epithelium becomes quiescent early during development. After the first postnatal week, there is no cell replacement or proliferation, and severe damage leads to permanent deafness. Supporting cells' trans-differentiation has been suggested as a way to regenerate cochlear hair cells after damage. However, they are also needed for proper functionality. Cdkn1b (p27Kip1) participates in the cochlear terminal mitosis state achieved during development. Its expression is maintained in adult supporting cells and its postnatal deletion has induced cochlear proliferation in vitro and in vivo. Therefore, its manipulation has been proposed as a feasible way to induce proliferation of supporting cells after birth. Nevertheless, the literature is scarce regarding feasible methods to directly decrease p27Kip1 in the clinical domain. The effects of p27Kip1 knockdown using viral vectors are not completely elucidated and no pharmacological approaches to decrease p27Kip1 in the cochlea have been tested in vivo before. This study explores the ability of p27Kip1 messenger knockdown and pharmacological transcriptional inhibition to induce proliferation of supporting cells in the P0 neonatal rat cochlea in vivo. Respectively, lentiviral vectors transducing shRNA against p27Kip1 were administered into the scala media or Alsterpaullone 2-Cyanoethyl into the round window niche. Cell markers and gene expression were assessed through immunostaining and qRT-PCR. Despite both methods significantly decreasing p27Kip1 expression in vivo, signs of toxicity in the organ of Corti were not found; however, relevant proliferation was not found either. Finally, cochlear damage was added to increase the response in vitro, achieving only a mild to moderate proliferation induction. We conclude that our approaches were not able to stimulate the recall of supporting cell proliferation despite significantly decreased p27Kip1 levels in vivo. Considering the evaluation of the cochlea at a very responsive stage, we propose that the level of isolated modification of p27Kip1 expression in living mammals achievable through these approaches is insufficient to induce proliferation of supporting cells. Future proliferation induction experiments in the cochlea should study other methods and genes.
Asunto(s)
Proliferación Celular , Cóclea/metabolismo , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Células Laberínticas de Soporte/metabolismo , Animales , Animales Recién Nacidos , Benzazepinas/farmacología , Proliferación Celular/efectos de los fármacos , Cóclea/efectos de los fármacos , Cóclea/patología , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/genética , Regulación hacia Abajo , Indoles/farmacología , Células Laberínticas de Soporte/efectos de los fármacos , Células Laberínticas de Soporte/patología , Interferencia de ARN , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Ratas Sprague-Dawley , Transducción de Señal , Técnicas de Cultivo de TejidosRESUMEN
INTRODUCTION: In daily life biological systems are usually exposed to magnetic field forces at different intensities and frequencies, either directly or indirectly. Despite negative results, the therapeutic use of the low dose magnetic field has been found in recent studies. The effect of magnetic field forces on cochlear cells is not clear in the literature. OBJECTIVE: In our study, we first applied in vivo pulsed magnetic fields to laboratory rats to investigate the effects on cochlea with distortion product otoacoustic emission test followed by histopathological examinations. METHODS: Twelve rats were included in this study, separated into two groups as study group and control group. The rats in the study group were exposed to 40Hz pulsed magnetic field for 1h/day for 30 days; the hearing of the rats was controlled by otoacoustic emission test. Also, their cochleas were removed and histochemical examination was performed by Caspase-3, Caspase-9, and TUNEL methods. RESULTS: A statistically significant difference was determined (p<0.05) when the hearing thresholds of the groups obtained by using 5714Hz and 8000Hz stimuli were compared by Kruskal-Wallis test. A significant reaction was observed in the study group, especially in the outer ciliated cells during immunohistochemical examinations by using Caspase-3 and Caspase-9 methods. A significantly positive difference was determined in the study group, especially at the outer ciliated cells and the support cells of the corti organ, when compared to the control group (p<0.05) by the TUNEL method. CONCLUSION: According to the results of our study, the very low dose magnetic field, which is considered to be used for therapeutic purposes recently, can cause both auditory function defects and histopathologic damage in cochlear cells.
Asunto(s)
Cóclea/patología , Campos Electromagnéticos/efectos adversos , Células Ciliadas Auditivas Externas/patología , Animales , Inmunohistoquímica , Masculino , Emisiones Otoacústicas Espontáneas , Ratas , Ratas Wistar , Estadísticas no ParamétricasRESUMEN
INTRODUCTION: The most common cause of tinnitus is the exposure to noise; in the case of adolescents, music is the main sound source they are exposed to. Currently, one of the hypotheses about the genesis of tinnitus is related to the deterioration in the functioning of the medial olivocochlear system (MOCS). AIM: The aim of this study was to determine the presence or absence of tinnitus in adolescents with normal hearing and to relate it to: (a) the functioning of the MOCS, by the contralateral suppression of the transient evoked otoacoustic emissions (TEOAEs) and (b) the musical general exposure (MGE). MATERIALS AND METHODS: A cross-sectional descriptive correlational study was conducted. The sample was composed by adolescents with ages between 14 and 15. Two questionnaires were administered, one in relation to the subjective report of tinnitus and the other in relation to recreational activities to know the MGE. RESULTS: The results showed that the amplitude of frequencies (1000, 1500, 2000, and 3000 Hz) and global amplitude of TEOAEs, with and without acoustic contralateral stimulation, were higher in the group without tinnitus, with a statistically significant difference (P < 0.05). The suppressive effect was higher in the group without tinnitus; however, there was no statistically significant difference. Contrastingly, a significant association (P < 0.05) between exposure to music and tinnitus was observed; 72.41% of the adolescents with high exposure to music had tinnitus. DISCUSSION AND CONCLUSION: The results of the present investigation provide a contribution to the hypothesis of "the participation of the MOCS." Furthermore, a high MGE can be considered a risk factor for the onset of tinnitus.
Asunto(s)
Cóclea/patología , Música , Núcleo Olivar/patología , Acúfeno/etiología , Adolescente , Argentina , Estudios Transversales , Femenino , Humanos , Masculino , Emisiones Otoacústicas Espontáneas , Factores de RiesgoRESUMEN
ABSTRACT INTRODUCTION: The vestibular system is responsible for body balance. There are substances that damage it, causing dizziness; these are termed vestibulotoxic substances. Agrochemicals have been investigated for ototoxicity because of studies that identified dizziness as a recurrent symptom among rural workers' complaints. OBJECTIVE: To histopathologically evaluate the vestibular system in guinea pigs exposed to an organophosphate, and to identify the drug's effects on this system. METHODS: Experimental clinical study. Eighteen guinea pigs were used; six of them poisoned with the organophosphate chlorpyrifos at doses of 0.5 mg/kg/day and seven of them at 1 mg/kg/day; and a control group of five guinea pigs was exposed to distilled water, all for 10 consecutive days. Later, ciliary tufts of saccule and utricle maculae were counted by scanning electron microscopy. RESULTS: Comparing the groups, a one-way ANOVA test for the variable "saccule" ( p = 0.0569) and a Kruskal-Wallis test for the variable "utricle" ( p = 0.8958) were performed, revealing no difference among groups in both variables. CONCLUSION: The histopathologic analysis of the vestibular system of guinea pigs exposed to an organophosphate showed no difference in the amount of ciliary tufts of saccule and utricle maculae at the doses tested, although the result for the variable "saccule" was considered borderline, showing a trend for significance.
RESUMO INTRODUÇÃO: O sistema vestibular é responsável pelo equilíbrio corporal. Existem substâncias que o danificam, causando tontura; são chamadas vestibulotóxicas. Agrotóxicos tornaram-se objeto de investigação da ototoxicidade a partir de pesquisas que apontaram tontura como sintoma recorrente entre as queixas de trabalhadores rurais. OBJETIVO: Constitui-se em avaliar a histopatologia do sistema vestibular de cobaias expostas a organofosforados, identificando os efeitos nesse sistema. MÉTODO: É um estudo clínico experimental, que utilizou 18 cobaias, sendo seis intoxicadas com organofosforadoclorpirifós na dose de 0,5 mg/kg/dia; sete na dose de 1 mg/kg/dia, e grupo controle com cinco cobaias expostas a água destilada, durante 10 dias consecutivos. Posteriormente realizou-se a contagem dos tufos ciliares nas máculas dos sáculos e utrículos através microscopia eletrônica de varredura. RESULTADOS: Na comparação intergrupos, para a variável sáculo realizou-se o teste ANOVA one-way (p = 0,0569); para a variável utrículo, utilizou-se o teste Kruskal-Wallis (p = 0,8958), revelando não haver diferença entre os grupos em ambas as variáveis. CONCLUSÃO: Análise histopatológica do sistema vestibular de cobaias expostas a organofosforado não demonstrou diferença na quantidade de tufos ciliares nas máculas dos sáculos e utrículos nas doses testadas, apesar do resultado para a variável sáculo ser considerado limítrofe mostrando uma tendência a significância.
Asunto(s)
Animales , Cobayas , Masculino , Cóclea/efectos de los fármacos , Insecticidas/toxicidad , Compuestos Organotiofosforados/toxicidad , Vestíbulo del Laberinto/efectos de los fármacos , Cóclea/patología , Modelos Animales de Enfermedad , Vestíbulo del Laberinto/patologíaRESUMEN
INTRODUCTION: The vestibular system is responsible for body balance. There are substances that damage it, causing dizziness; these are termed vestibulotoxic substances. Agrochemicals have been investigated for ototoxicity because of studies that identified dizziness as a recurrent symptom among rural workers' complaints. OBJECTIVE: To histopathologically evaluate the vestibular system in guinea pigs exposed to an organophosphate, and to identify the drug's effects on this system. METHODS: Experimental clinical study. Eighteen guinea pigs were used; six of them poisoned with the organophosphate chlorpyrifos at doses of 0.5mg/kg/day and seven of them at 1mg/kg/day; and a control group of five guinea pigs was exposed to distilled water, all for 10 consecutive days. Later, ciliary tufts of saccule and utricle maculae were counted by scanning electron microscopy. RESULTS: Comparing the groups, a one-way ANOVA test for the variable "saccule" (p=0.0569) and a Kruskal-Wallis test for the variable "utricle" (p=0.8958) were performed, revealing no difference among groups in both variables. CONCLUSION: The histopathologic analysis of the vestibular system of guinea pigs exposed to an organophosphate showed no difference in the amount of ciliary tufts of saccule and utricle maculae at the doses tested, although the result for the variable "saccule" was considered borderline, showing a trend for significance.
Asunto(s)
Cóclea/efectos de los fármacos , Insecticidas/toxicidad , Compuestos Organotiofosforados/toxicidad , Vestíbulo del Laberinto/efectos de los fármacos , Animales , Cóclea/patología , Modelos Animales de Enfermedad , Cobayas , Masculino , Vestíbulo del Laberinto/patologíaRESUMEN
UNLABELLED: To understand how the DNA answers to external agents such as cisplatin may be relevant to the diagnosis and treatment of hearing disorders caused by the administration of such drug. OBJECTIVES: To investigate the cisplatin influence on the cochlea and DNA of guinea pigs. MATERIAL AND METHODS: Experimental study carried out with 12 guinea pigs (Cavia porcellus). The inclusion criterion was the presence of Preyer's reflex and distortion-product otoacoustic emissions. Guinea pigs were divided into two groups: Control Group (CG)--made up of six guinea pigs, to which we administrated saline solution during six consecutive days, intraperitoneally; and a Study Group (SG)--made up of six guinea pigs, to which we administrated cisplatin during six consecutive doses of 3mg/kg/day intraperitoneally. Twenty-four hours after the last administration of cisplatin the guinea pigs were slaughtered, blood samples were collected and the cochleae were removed. RESULTS: The administration of cisplatin did not cause identifiable changes to the DNA. Histological analysis showed changes in the organ of Corti and spiral ganglion. CONCLUSION: Cisplatin causes changes in cochlear histology, such as the loss of the normal micro-cytoarchitecture of the organ of Corti, and reduction of neurons of the spiral ganglion with cell alterations, however, DNA damage was not detected.
Asunto(s)
Antineoplásicos/toxicidad , Cisplatino/toxicidad , Cóclea/efectos de los fármacos , Daño del ADN , ADN/efectos de los fármacos , Animales , Cóclea/patología , Cobayas , Pruebas de MutagenicidadRESUMEN
Conhecer as respostas do DNA aos agentes externos como a cisplatina pode ser relevante para o diagnóstico e tratamento das alterações auditivas causadas pela administração deste fármaco. OBJETIVOS: Verificar a influência da cisplatina sobre a cóclea e o DNA de cobaias. MATERIAL E MÉTODO: Estudo experimental executado com 12 cobaias (Cavia porcellus). O critério de inclusão de cobaias na amostra foi a presença de reflexo de Preyer e emissões otoacústicas produto de distorção (EOAPDs). As cobaias foram dividas em dois grupos: Grupo controle (GC) - composto de seis cobaias, às quais foi administrada solução fisiológica por seis dias consecutivos, via intraperitoneal; Grupo estudo (GE) - composto por seis cobaias, às quais foi administrada cisplatina em seis doses consecutivas de 3mg/kg/dia via intraperitoneal. Vinte e quatro horas após a última aplicação de cisplatina as cobaias foram sacrificadas, foi coletada amostra sanguínea e as cócleas foram removidas. RESULTADOS: Administração de cisplatina não provocou alterações genotóxicas. A análise histológica mostrou alterações no órgão de Corti e gânglio espiral. CONCLUSÃO: A cisplatina provoca alterações na histologia coclear como perda da microcitoarquitetura normal do órgão de Corti e redução dos neurônios do gânglio espiral com alterações celulares. No entanto, não foram detectados danos genotóxicos.
To understand how the DNA answers to external agents such as cisplatin may be relevant to the diagnosis and treatment of hearing disorders caused by the administration of such drug. OBJECTIVES: To investigate the cisplatin influence on the cochlea and DNA of guinea pigs. MATERIAL AND METHODS: Experimental study carried out with 12 guinea pigs (Cavia porcellus). The inclusion criterion was the presence of Preyer's reflex and distortion-product otoacoustic emissions. Guinea pigs were divided into two groups: Control Group (CG) - made up of six guinea pigs, to which we administrated saline solution during six consecutive days, intraperitoneally; and a Study Group (SG) - made up of six guinea pigs, to which we administrated cisplatin during six consecutive doses of 3mg/kg/day intraperitoneally. Twenty-four hours after the last administration of cisplatin the guinea pigs were slaughtered, blood samples were collected and the cochleae were removed. RESULTS: The administration of cisplatin did not cause identifiable changes to the DNA. Histological analysis showed changes in the organ of Corti and spiral ganglion. CONCLUSION: Cisplatin causes changes in cochlear histology, such as the loss of the normal micro-cytoarchitecture of the organ of Corti, and reduction of neurons of the spiral ganglion with cell alterations, however, DNA damage was not detected.
Asunto(s)
Animales , Cobayas , Antineoplásicos/toxicidad , Cisplatino/toxicidad , Cóclea/efectos de los fármacos , ADN , Daño del ADN , Cóclea/patología , Pruebas de MutagenicidadRESUMEN
OBJECTIVE: To analyze temporal bones of deaf Dalmatian dogs from 5 days after birth to adulthood to better understand the pathogenesis of cochleosaccular dysplasia. METHODS: This is an experimental animal histopathological temporal bone study that included two groups of temporal bones. Group I consisted of 41 temporal bones from deaf Dalmatian dogs and group II of 25 temporal bones from 15 "normal" aged-matched, hearing Black Labradors. Morphometric analysis included: stria vascularis and spiral ligament area measurements, and cell counts of spiral ganglion, Scarpa's ganglion, and hair cells of saccular macula. RESULTS: The following findings were significantly less in deaf Dalmatian group compared to hearing Labradors: (1) cellular area of the stria vascularis in all cochlear turns; (2) cellular area of spiral ligament in the inferior part of the basal turn; (3) cellular density of spiral ganglion cells within segments III and IV; (4) number of Scarpa's ganglion cells; and (5) density of saccular hair cells types I and II. A borderline negative correlation was found between average density of spiral ganglion cells of segments III and IV and age in group I. Young deaf animals showed some cochlear hair cells, however in adult dogs all hair cells were replaced by supporting cells. CONCLUSION: General pattern of cochleosaccular dysplasia is variable, even when only one etiology, the genetic one, is involved. The gradual degeneration of inner ear elements in the cochleosaccular degeneration might indicate that early intervention might be crucial to stop the progression of cochleosaccular dysplasia.
Asunto(s)
Cóclea/patología , Sordera/congénito , Hueso Temporal/patología , Animales , Perros , Células Ciliadas Auditivas Internas/patología , Órgano Espiral/patología , Sáculo y Utrículo/patología , Ganglio Espiral de la Cóclea/patología , Estría Vascular/patologíaRESUMEN
UNLABELLED: Cisplatin is a chemotherapy agent frequently used to treat different types of neoplasia. Ototoxicity is one of the side-effects which cause significant morbidity and limits its use. This study aimed at assessing the role of apoptosis in cisplatin-induced ototoxicity. DESIGN: experimental study. MATERIALS AND METHODS: male Wistar rats were treated with intraperitoneal cisplatin, in the doses of 24 and 16 mg/kg. The animals were assessed by means of distortion product evoked otoacoustic emissions (DPEOAE) or brainstem evoked auditory potentials (BEAP) in the third (D3) and fourth (D4) days after drug infusion onset. Following that, their cochleas were removed for immunohistochemical studies of apoptosis - TUNEL method. RESULTS: the group treated with 24 mg/kg showed a significant reduction in DPEOAE amplitude, and such fact was not seen with the 16 mg/kg. Both doses caused an increase in BEAP electrophysiological threshold in D3 and D4. Apoptosis was the injury mechanism responsible for the cisplatin-induced ototoxicity - 16 mg/kg dose, when the animals were assessed on D3. CONCLUSION: apoptosis may be involved in the cisplatin-induced ototoxicity, depending on the dose and time of injury assessment.