The protective effects of whortleberry extract against cisplatin-induced ototoxicity in rats / Efeitos protetores do extrato de uva-do-monte contra a ototoxicidade induzida por cisplatina em ratos

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.

The Effect of Methylphenidate on the Hearing of Children with Attention Deficit Hyperactivity Disorder

Abstract Introduction There has been a sudden idiopathic hearing loss case presented after methylphenidate treatment in a child with attention deficit hyperactivity disorder (ADHD). Objective This study was performed to reveal the probable ototoxic side effects of methylphenidate use in patients with ADHD. Methods Thirty pediatric patients with ADHD were included in the study. Pure tone audiometry, speech discrimination scores, waves I, III, V absolute latencies and waves IIII, I-V, III-V interpeak latencies at the 80 dB nHL intensity after click stimulus auditory brainstem response (ABR) results were compared before and 3 months after methylphenidate treatment. Results There were no statistically significant difference between pretreatment and posttreatment pure tone and speech audiometry findings and ABR results (p > 0.05 for all parameters). Conclusion Methylphenidate can be regarded as a safe drug regarding ototoxic side effects. Additional studies with a larger sample size and longer follow-up may be needed.

Sequential analysis as a tool for detection of amikacin ototoxicity in the treatment of multidrug-resistant tuberculosis / Análise sequencial como ferramenta na detecção da ototoxicidade da amicacina no tratamento da tuberculose multirresistente

ABSTRACT Objective: To investigate early detection of amikacin-induced ototoxicity in a population treated for multidrug-resistant tuberculosis (MDR-TB), by means of three different tests: pure-tone audiometry (PTA); high-frequency audiometry (HFA); and distortion-product otoacoustic emission (DPOAE) testing. Methods: This was a longitudinal prospective cohort study involving patients aged 18-69 years with a diagnosis of MDR-TB who had to receive amikacin for six months as part of their antituberculosis drug regimen for the first time. Hearing was assessed before treatment initiation and at two and six months after treatment initiation. Sequential statistics were used to analyze the results. Results: We included 61 patients, but the final population consisted of 10 patients (7 men and 3 women) because of sequential analysis. Comparison of the test results obtained at two and six months after treatment initiation with those obtained at baseline revealed that HFA at two months and PTA at six months detected hearing threshold shifts consistent with ototoxicity. However, DPOAE testing did not detect such shifts. Conclusions: The statistical method used in this study makes it possible to conclude that, over the six-month period, amikacin-associated hearing threshold shifts were detected by HFA and PTA, and that DPOAE testing was not efficient in detecting such shifts.

RESUMO Objetivo: Verificar a detecção precoce de ototoxicidade causada pelo uso de amicacina numa população tratada para tuberculose multirresistente (TBMR) por meio da realização de três testes distintos: audiometria tonal liminar (ATL), audiometria de altas frequências (AAF) e pesquisa de emissões otoacústicas por produto de distorção (EOAPD). Métodos: Estudo longitudinal de coorte prospectiva incluindo pacientes de ambos os sexos, com idade entre 18 e 69 anos, com diagnóstico de TBMR pulmonar e que necessitaram utilizar amicacina por seis meses em seu esquema medicamentoso antituberculose pela primeira vez. A avaliação auditiva foi realizada antes do início do tratamento e depois de dois e seis meses do início do tratamento. A análise dos resultados foi realizada por meio de análise estatística sequencial. Resultados: Foram incluídos 61 pacientes, mas a população final foi constituída de 10 pacientes (7 homens e 3 mulheres), em razão da análise sequencial. Ao se comparar os valores das respostas dos testes com aqueles encontrados na avaliação basal, foram verificadas mudanças nos limiares auditivos compatíveis com ototoxicidade após dois meses de tratamento através da AAF e após seis meses de tratamento através da ATL. Entretanto, essas mudanças não foram verificadas através da pesquisa de EOAPD. Conclusões: Ao se considerar o método estatístico utilizado nessa população, é possível concluir que mudanças nos limiares auditivos foram associadas ao uso da amicacina no período de seis meses por meio de AAF e ATL e que a pesquisa de EOAPD não se mostrou eficiente na identificação dessas mudanças.

Effect of interferon treatment on hearing of patients with chronic hepatitis C

Some reports in the literature have linked interferon therapy for the treatment of hepatitis C [HCV] with hearing loss. The aim of this study has been to examine the effects of interferon therapy on hearing of patients treated for HCV. Patients were recruited according to preset inclusion criteria from two centers. All patients received standard dose pegylated interferon [PEG-IFN alpha-2b or alpha-2a] plus ribavirin [RBV]. All patients had pure-tone audiometry [PTA], tympanogram and distortion-product otoacoustic emission [DPOAE] before treatment, three months after initiation of treatment, and three months after completion of treatment. Twenty one patients were prospectively recruited. The mean age was 45.7 years. The male to female ratio was 1.1:1. The mean PTA was 15.9 +/- 5.3 before treatment, 17.4 +/- 6.1 during treatment and 16.5 +/- 5.1 after treatment. The differences between pre and mid, pre and post, as well as mid and post were not significantly different [P>0.05] in all audiological assessments. Our results indicate that PEG-IFN/RBV therapy does not have any impact on the hearing thresholds of patients with HCV

Hearing profile in children with bacterial meningitis treated with dexamethasone

Thirty children with proved bacterial meningitis were included in this prospective clinical study aiming at assessment of the role of dexamethasone therapy in reducing the incidence of hearing impairment as a complication of bacterial meningitis. The patients were divided into two equal groups, the first group received antibiotics alone while the second group received dexamethasone for 4 days beside the appropriate antibiotics. Hearing evaluation was done for all patients within 4-6 weeks after discharge. Hearing evaluation included basic audiologic evaluation namely pure tone audiometry, speech audiometry and tympanometry as well as brainstem audiometry some patients. Hearing evaluation revealed that dexamethasone reduces the incidence of hearing impairment particularly in children with meningitis due to hemophilus influenzae. The overall incidence of sensorineural hearing loss and conductive hearing loss in the first group was 6.7% and 23.3% respectively compared to an incidence of 24% and 43.4% respectively in the second group. Our study recommends the use of dexamethasone in all cases of bacterial meningitis to reduce the incidence of hearing loss

Vitiligo: an added risk factor to aminoglycosides ototoxicity

Hearing assessment in 30 vitiligo patients revealed the presence of mild to moderate subclinical high tone sensorineural deafness in 11 patients [36.7%]. Auditory brain stem response [ABR] was done for patients with moderate affection. In these patients, there was a significant decrease of the latency of the peak of wave 1 indicating a numerical decrease of melanocytes in the inner ear which may result in cochlear sensorineural hearing loss. There was also a significant increase of the interpeak latency of waves I-III. This can be explained by the presence of abnormal synaptic activity from the auditory nerve to the superior olivary nucleus. The present work suggests that destruction of the melanocytes in the inner ear of vitiligo patients is responsible for disturbance of the auditory function. This finding might warrant tagging vitiligo patients against further auditory damage by the use of ototoxic drugs like aminoglycosides

effects of treatment with praziquantel on hearing

Praziquantel is a commonly used broad spectrum antihelminthic drug. It has totally replaced the antimonial compounds in the treatment of schistosomiasis. In this work 109 patients were included to study the audiometric changes produced by the drug in the routine treatment regimen for schistosomiasis. Pretreatment pure tone audiograms were obtained for all patients on air and bone conduction. They were then repeated after 24 hours of treatment, one week and one month after treatment. Eight patients out of 109 developed marked significant changes in their audiogram, defined as more than 15 dB from previous readings. The results concluded that praziquantel treatment can cause mild audiometric changes mainly in the higher frequencies for a transient period which was followed by a return to normal hearing. Full audiological assessment to all patients undergoing treatment with praziquantel is highly recommended