Effect of melatonin on otoprotection in rodents: a systematic review with meta-analysis

Abstract Objectives: To determinate the otoprotective efficacy of melatonin.in experimental models of rodents through a systematic review of the literature. Methods: Altogether, 154 articles were found in four databases. The PICOS strategy (Population, Intervention, Comparison, and Outcome) was used to define the eligibility criteria. Studies that met the inclusion criteria for the second step were included in a qualitative synthesis. Each study type was analyzed with the CAMARADES quality of assessment's checklist and the SYRCLE RoBS risk of bias. Results: Seven articles were selected, and four were included in the meta-analysis. It was possible to obtain seven outcomes according to the standard auditory frequencies presented among the studies, considering a minimum of three standard frequencies. The outcomes analyzed were for the frequencies of 1500, 2000, 3000, 4000, 5000, 6000, and 8000 Hz. Conclusion: Melatonin can provide protection against the ototoxic effects of cisplatin and aminoglycosides at 5000 Hz, 6000 Hz, and 8000 Hz, thereby minimizing the reduction in Otoacustic Emissions (OAE) amplitude. The same effect was not observed in the lower frequencies. Despite the limited number of studies that were evaluated, the results appeared consistent in higher frequencies. However, the methodology of the available studies did not meet the necessary methodological rigor that promotes the safe replicability of these studies.

Progress in the mechanisms and preventive measures of cisplatin-induced ototoxicity / 国际儿科学杂志

Cisplatin is a broad-spectrum and highly effective chemotherapeutic agent, with a dose-dependent therapeutic effect.Unfortunately, high-does therapy is limited by ototoxicity, nephrotoxicity and neurotoxicity.Ototoxicity is a common and serious complication after cisplatin chemotherapy, which has greatly debilitating effect on patients′ quality of life.Currently, there are no FDA-approved drugs available to prevent cisplatin-induced hearing loss.In recent years, domestic and international studies on cisplatin-induced ototoxicity have revealed many new mechanisms and therapeutic targets.Many candidate agents have shown good hearing protection.Moreover, local drug delivery methods are being optimized, promising for further translations to clinical applications.

Ototoxicidad inducida por quimio-radioterapia basada en platinos: una revisión / Ototoxicity induced by platinum compounds-based chemoradiotherapy: a review

RESUMEN Los análogos del platino, como el cisplatino, y la radioterapia son usados de forma individual y en conjunto para el tratamiento de diversas neoplasias en población adulta y pediátrica. Sin embargo, el uso de estos tratamientos puede generar ototoxicidad, especialmente cuando son usados de forma combinada para neoplasias que comprometen cabeza y cuello, manifestándose principalmente como una hipoacusia progresiva e irreversible que compromete la calidad de vida. Diversos mecanismos han sido propuestos para explicar el daño en las estructuras auditivas generado por estos tratamientos, incluyendo la producción de especies reactivas del oxígeno y la inflamación, desencadenando muerte celular. Si bien distintas estrategias otoprotectoras han sido probadas en humanos, es aún incierta su efectividad y seguridad en combinación con los tratamientos oncológicos. El objetivo de la siguiente revisión es proporcionar una visión general y actualizada de la ototoxicidad inducida por quimio-radioterapia basada en platinos, discutiendo sus bases, características clínicas, potenciales tratamientos y estrategias preventivas que se han desarrollado en los últimos años.

ABSTRACT Platinum analogues, such as cisplatin, and radiotherapy are used separately or in combination to treat several neoplasms in pediatric and adult populations. Nonetheless, the use of these treatments may lead to ototoxicity, especially when these treatments are concomitantly used to treat head and neck cancers, which can manifest as progressive and irreversible hearing loss that decreases quality of life. Several mechanisms have been proposed in order to explain the damage to the auditory structures induced by these treatment modalities, including: reactive oxygen species production and inflammation, leading to cell death. Although several otoprotective strategies have been attempted in humans, their effectiveness and security are unclear. The objective of this review is to provide an updated and general overview on platinum-based chemoradio-therapy induced ototoxicity, discussing its basis, clinical features, potential treatments and preventive strategies developed in recent years.

Medio militar y trastornos auditivos inducidos por ruido / The military environment and noise-induced hearing impairments

En el medio militar el personal se ve sometido a los más altos niveles de ruido; se considera que las detonaciones de las armas de fuego superan en intensidad a todos los ruidos industriales. Este trabajo pretende abordar los factores de riesgo y vulnerabilidad asociados a la exposición al ruido en el ambiente militar, los aspectos más actuales relacionados con la lesión auditiva inducida por ruido y su protección. Se realizó una revisión de los artículos más representativos mediante la base de datos Medline e Hinari, se empleó para la búsqueda y creación de la bibliografía el gestor personal de referencias bibliográficas Procite, referencias al tema en revistas, tesis y referencias en Internet mediante el buscador Google. Los resultados reafirman la vulnerabilidad del personal militar a padecer algún tipo de lesión del aparato auditivo inducida por ruido, originado por los niveles de ruido elevado que se producen en el medio militar, la necesidad de enfocar de forma multidisciplinaria este tipo de lesiones y la importancia de implementar sistemas de protección auditiva eficientes, con el fin de elevar la calidad de vida de los expuestos a ruido y evitar que se produzca la discapacidad auditiva, considerando que la mejor opción es su prevención.

Extremely high noise levels are characteristic of the military environment. Firearm detonations are considered to exceed the intensity of any industrial noise. The paper approaches the risk factors and vulnerabilities associated with exposure to noise in the military environment, as well as the most recent notions about noise-induced hearing injury and hearing protection. A review was conducted of the most representative papers on the topic using databases Medline and Hinari. Bibliography lists were searched for and created using Procite personal bibliographic reference manager. Google search engine was used to find references to the topic in journals, theses and Internet references. Results confirm the vulnerability of military personnel to suffer from noise-induced hearing injuries resulting from the high noise levels occurring in the military environment, the need to approach such injuries in a multidisciplinary manner, and the importance of implementing efficient hearing protection systems, with a view to improving the quality of life of persons exposed to noise and preventing hearing impairment, based on the certainty that prevention is always the best option.

The role of hyperbaric oxygen therapy (HOT) as an otoprotection agent against cisplatin ototoxicity / Efeito otoprotetor da oxigenoterapia hiperbárica na toxicidade causada pela cisplatina

PURPOSE: Hyperbaric oxygen therapy (HOT) consists of intermittent inhalations of 100 percent oxygen at a pressure higher than 1 atm. It is an important adjuvant therapy in pathological processes like soft tissue infections, radiation injury, gas gangrene, osteomyelitis and decompressive diseases. Cisplatin, a potent antineoplastic drug, widely used in cancer therapy is highly ototoxic causing bilateral, irreversible damage to the hearing of high frequency sounds (4-8 KHz). OBJECTIVE:This experimental study conducted at the Faculty of Medicine of Ribeirao Preto, University of Sao Paulo aims to evaluate Hyperbaric Oxygen Therapy as an otoprotection agent against drug toxicity. METHODS: Albino guinea pigs were divided into two groups: in Group A, 5 animals (10 cochlea) received cisplatin, i. p., 8.0 mg/kg/day during three days and afterwards were submitted to HOT; in Group B, 3 animals (6cochlea) received cisplatin, i. p. 8.0mg/kg/day during three days. Guinea pigs were evaluated by acoustic otoemissions (AOE) and scanning electron microscopy (SEM). RESULTS: Group B animals showed loss of auditory functions as measured by AOE and distorted outer hair cells by SEM. In Group A, outer hair cells shown by SEM images were mostly preserved. CONCLUSION: It is presumed that Hyperbaric Oxygen Therapy has a protector effect against cisplatin ototoxicity.

INTRODUÇÃO: A Oxigenoterapia hiperbárica (OHB) envolve a inalação de oxigênio a 100 por cento sob uma pressão maior que 1 atm. E um importante modo de terapia adjuvante para processos patológicos, tais como: infecção de partes moles, lesões actínicas, gangrena gasosa, osteomielite e doença descompressiva. A cisplatina e uma potente droga antineoplásica largamente utilizada para o tratamento de câncer. A ototoxicidade e um importante efeito colateral desta droga, causando dano irreversível, bilateral, na capacidade de ouvir sons de alta freqüência (4 - 8 KHz). Este estudo experimental, realizado na Faculdade de Medicina de Ribeirao Preto da Universidade de São Paulo nos anos de 2005 e 2006. Objetivo: Avaliar o papel da Oxigenoterapia Hiperbárica como agente otoprotector contra a toxicidade de drogas. MÉTODOS: Cobaias albinas divididas em 2 grupos Grupo A: com 5 cobaias (10 cócleas) que receberam cisplatina 8,0 mg/kg/dia, via intraperitoneal por 3 dias, submetidas posteriormente a OHB. Grupo B: com 3 cobaias (6 cócleas) que receberam cisplatina 8,0 mg/kg/dia, via intraperitoneal por 3 dias. As cobaias foram avaliadas através de otoemissões acústicas (OEA) e por microscopia eletrônica de varredura (MEV). Resultados: Encontramos no grupo B perda da função auditiva medida pela OEA e distorção das células ciliares externas a MEV. No grupo A, a MEV as células ciliares externas foram preservadas em sua grande maioria. CONCLUSÃO: Assim podemos supor que a Oxigenoterapia Hiperbárica tem um efeito otoprotetor contra a ototoxicidade induzida pela cisplatina.