Dose-dependent effect of 8-day cisplatin administration upon the morphology of the albino guinea pig cochlea

Cardinaal, Remco M; Groot, John C.M.J. de; Huizing, Egbert H.; Veldman, Jan E.; Smoorenburg, Guido F.

doi:10.1016/s0378-5955(00)00059-9

Cited by 79 publications

(81 citation statements)

References 25 publications

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“…Confirming observations by Cardinaal et al 12 , this study showed that cisplatin induces dose-dependent cochlear alterations. High drug dosages in short periods of time (8mg/kg/day, three days) led to cellular lesions and significant hair damage in outer hair cells.…”

Section: Discussionsupporting

confidence: 91%

“…Concomitant use of cisplatin and Hyperbaric Oxygen Therapy is contra-indicated but in this case cisplatin was used as an efficient lesion producer in cochlea outer hair cells in a short time 12 and the hyperbaric therapy only started 48 hours after the last drug dose.…”

Section: Discussionmentioning

confidence: 99%

“…It was shown that levels of glutathione (GSH) and antioxidant enzymes as superoxide dismutase (SOD), catalase, GSH peroxidase and GSH reductase are reduced in these tissues leading to lipid peroxidation, thus, to cellular toxicity. 3,12,15,17,18 Anti-oxidant effects of Hyperbaric Oxygen Therapy have been observed through decrease in neutrophils adhesion 22 and increased NO production, which combine with superoxide anions blocking their effects. 23 In experimental pancreatitis in rats, it was demonstrated that HOT promotes an elevation in levels of super oxide dismutase (SOD) with metabolization of oxidant radicals.…”

Section: Discussionmentioning

confidence: 99%

“…The possible lesion producing mechanisms include calcium channel blockades in outer hair cells, supporting cells, stria vascularis as well as in the spiral ganglion. [7][8][9][10][11][12][13] The last decade has seen studies aiming at a better understanding of the anti-oxidant mechanisms of outer hair cells, compromised by ototoxic drugs like aminoglycosides and cisplatin. Several potential oto protective drugs, which act blocking lesion producing mechanisms to the antioxidant system of the outer hair cells have been tested.…”

Section: Introductionmentioning

confidence: 99%

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The role of hyperbaric oxygen therapy (HOT) as an otoprotection agent against cisplatin ototoxicity

et al. 2008

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Purpose: Hyperbaric oxygen therapy (HOT) consists of intermittent inhalations of 100% 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.Key words: Hyperbaric Oxygen Therapy. Ototoxicity. Otoprotection. Cisplatin. RESUMOIntrodução: A Oxigenoterapia hiperbárica (OHB) envolve a inalação de oxigênio a 100% 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.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The role of hyperbaric oxygen therapy (HOT) as an otoprotection agent against cisplatin ototoxicity

et al. 2008

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“…Alguns autores sugerem a ocorrência de um bloqueio na transdução dos canais de cálcio destas células, outros estudos mostram lesões às células ciliadas internas, às células suportes e "stria vascularis", bem como o gânglio espiral. [10][11][12][13][14][15][16][17] A cisplatina causa uma perda auditiva bilateral e irreversível em humanos, com zumbido associado e comprometendo as altas freqüências (4.000 Hz a 8.000 Hz). 1,2,4,8,18 As formas de se estudar os efeitos da toxicidade coclear têm se dirigido às alterações eletrofisiológicas detectadas pelo Potencial Evocado de Tronco Cerebral (BERA) e Potencial Endococlear.…”

Section: Introductionunclassified

Ototoxicidade da cisplatina e otoproteção pelo extrato de ginkgo biloba às células ciliadas externas: estudo anatômico e eletrofisiológico

Hyppolito¹,

Oliveira²,

Rossato³

et al. 2003

Rev. Bras. Otorrinolaringol.

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A Cisplatina é uma potente droga antineoplásica, largamente utilizada para o tratamento do câncer, tanto em adultos quanto em crianças. Dentre seus efeitos colaterais, a ototoxicidade se apresenta como um dos mais importantes e leva à perda auditiva irreversível, bilateral, para as altas freqüências (4KHz#8KHz). Estudos têm tentado identificar drogas que, associadas à cisplatina possam atuar como otoprotetores. Sabe-se que o mecanismo da ototoxicidade pela cisplatina está relacionado a alterações nos mecanismos antioxidantes das células ciliadas, principalmente as células ciliadas externas da cóclea. Objetivo: Nossa proposta foi de avaliar através de emissões otoacústicas, por produtos de distorção (EOAPD) e por microscopia eletrônica de superfície (ME), a ação do extrato de ginkgo biloba (EGB 761), que tem conhecida ação antioxidante, como possível otoprotetor, utilizando como modelo experimental cobaias albinas. Forma de estudo: Experimental. Material e método: Observamos EOAPD presentes pré e pós tratamento no grupo EGB (100 mg/Kg/dia via oral) e 90 minutos após cisplatina (80 mg/Kg/dia via intraperitoneal) por 8 dias. Resultado: Houve também manutenção da arquitetura ciliar nas células ciliadas externas em todas as espiras da cóclea, enquanto que no grupo tratado somente com cisplatina (80 mg/ Kg/dia via intraperitoneal) por 8 dias, houve desaparecimento das EOAPD pós tratamento, com desaparecimento dos cilios das células ciliadas externas e distorção na arquitetura dos cílios remanescentes à ME. Conclusão: Concluímos que a EGB, por sua ação antioxidante, atua como fator otoprotetor à ototoxicidade pela cisplatina, devendo ser testada tal ação na prática clínica em pacientes que utilizam a cisplatina, pois o uso do EGB está extremamente difundido no tratamento de diferentes doenças. ci splatin is an antineoplastic drug for cancer treatment in children and adults. The side effects of cisplatin ototoxycity are important with irreversible auditory and bilateral damage to high frequencies (4kHz -8 kHz). Reports recognize some drugs that are associated with cisplatin to obtain an otoprotector effect. The ototoxycity mechanisms of cisplatin are related to injury of conduct the hair cell oxidation mechanism, with particular injury to outer hair cells. Aim: We intend to studies using otoacoustic emissions -distortion products (DPOEA) and scanning microscopy to verify the action of ginkgo biloba (GBE-761) that has well known antoxidizing characteristics, that can function like otoprotector effects. Study design: Experimental. Material and method: We use an experimental guinea pig model. We found DPOEA positive before and after treatment in the GBE group (100 mg/ Kg/ day -oral) and after 90 minutes cisplatin (8,0 mg/ Kg/ day -intraperitoneal -8 consecutive days). Results: The normal cilium architecture of outer hair cells was supported in all cochlear spirals and in the group treated only with cisplatin (8,0 mg/ Kg/ day -intraperitoneal -8 consecutive days), the DPOEA was not present and strong injury to cilium of out...

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Review: Ototoxic Characteristics of Platinum Antitumor Drugs

Ding

Allman

Salvi

2012

The Anatomical Record

119

104

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Cisplatin, carboplatin, nedaplatin, and oxaliplatin are widely used in contemporary oncology; however, their ototoxic and neurotoxic side effects are quite different as discussed in this review. Cisplatin is considered the most ototoxic, but despite its reputation, the magnitude of hair cell loss that occurs with a single, large drug bolus is limited and confined to the base of the cochlea. For all of these platinum compounds, a major factor limiting damage is drug uptake from stria vascularis into the cochlear fluids. Disrupting the blood-labyrinth barrier with diuretics or noise exposure enhances drug uptake and significantly increases the amount of damage. Combined treatment with ethacrynic acid (a loop diuretic) and cisplatin results in rapid apoptotic hair cell death characterized by upregulation of initiator caspase-8 and membrane death receptor, TRADD, followed by downstream executioners, caspase-3 and caspase-6. Unlike cisplatin, nedaplatin and oxaliplatin are highly neurotoxic when applied to cochlear cultures preferentially damaging auditory nerve fibers at low concentrations and hair cells at high concentrations. Carboplatin, considered far less ototoxic than cisplatin, is paradoxically highly toxic to chinchilla inner hair cells and type I spiral ganglion neurons; however, at high doses it also damages outer hair cells. Hair cell death from cisplatin and carboplatin is characterized in its early stages by upregulation of p53; blocking p53 expression with pifithrin-a prevents hair cell death. Major differences in the toxicity of these four platinum compounds may arise from several different metal transporters that selectively regulate the influx, efflux, and sequestration of these drugs.

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Dose-dependent effect of 8-day cisplatin administration upon the morphology of the albino guinea pig cochlea

Cited by 79 publications

References 25 publications

The role of hyperbaric oxygen therapy (HOT) as an otoprotection agent against cisplatin ototoxicity

The role of hyperbaric oxygen therapy (HOT) as an otoprotection agent against cisplatin ototoxicity

Ototoxicidade da cisplatina e otoproteção pelo extrato de ginkgo biloba às células ciliadas externas: estudo anatômico e eletrofisiológico

Review: Ototoxic Characteristics of Platinum Antitumor Drugs

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