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

Abstract

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.

Oxygenation inhibits ovarian tumor growth by down-regulating STAT3 and cyclin-D1 expressions

“…35 Aydinoz et al 34 reported significant body-weight loss in cisplatin as well as cisplatin + HBO-treated rats. However, the most dramatic weight loss was observed in the cisplatin only-treated group.…”

“…Atasoyu et al 33 have observed a high mortality rate in rats receiving cisplatin and cisplatin + HBO. Further, Yassuda et al 35 noted that 2 of 5 guinea pigs treated with combination therapy died prior to the completion of the study. Thus far, the evidence suggests that even under differing treatment conditions, combination therapy utilizing cisplatin and HBO should be avoided.…”

The Effects of Hyperbaric Oxygen Therapy Against Streptomycin Ototoxicity

“…Among them, anti-free radical agents are becoming increasingly important [4][5]. Hyperbaric oxygen (HBO) therapy, having an important antioxidant activity, is based on inhalation of 100% oxygen under pressures above 1 atm (pressurized between 1.5 and 3.0 atmosphere absolute) in a pressure chamber [7,8]. Due to its antioxidant property, HBO has been considered to prevent ototoxicity.…”

“…Although the mechanism of HBO therapy in inner ear has not been still fully understood, today, it is an important adjuvant therapy and being increasingly used in a variety of disorders, such as severe anaemia, decompressive diseases, arterial gas embolism, carbon monoxide poisoning, stimulant of wound healing on refractory wounds, gas gangrene, radiation injury, necrotizing infections, and chronic osteomyelitis [7][8][9]. It has been also used in the management of acute ischemia-related disorders like acute sensorineural hearing loss such as sudden deafness, and acute noise trauma [8,[10][11][12][13][14][15]. But to the best of our knowledge, no study to date have investigated the possible protective effect of HBO against to ototoxic effect of aminoglycoside.…”

Normobaric hyperoxia preconditioning ameliorates cisplatin nephrotoxicity

“…21 Interestingly, in an experimental study, HBO therapy results in an otoprotection effect against Cisplatin-induced ototoxicity. 22 In a series of 89 liver transplant patients, donor hyperoxygenation before organ harvest, defined as a PaO 2 value greater than 150 mmHg, was associated with good graft outcome. 23 It could be assumed that the hyperoxia preconditioning of donor has reduced liver ischemic reperfusion injury.…”