本研究来自第四军医大学和天津军医大学的研究,发表在International Journal of Pediatric Otorhinolaryngology。

 顺铂是一种广泛应用于临床的抗癌药物， 该药物可以通过诱导活性氧导致耳毒性。该药物不仅有耳毒性，而且也具有肾脏毒性。最近报道氢气作为一种新型的抗氧化物质，选择性中和毒性最强的活性氧——羟基自由基。该研究的目的是探讨氢气对顺铂耳毒性的保护作用。

腹腔注射顺铂16 mg/kg制备动物模型，注射顺铂后1小时和6小时分别给动物呼吸1小时含2%氢气的空气。用听觉脑干诱发电位评价动物听力功能，Phalloidin染色研究听毛细胞的病理变化，并检测血清和内耳组织氧化损伤指标。

脑干诱发电位研究结果发现氢气治疗可以显著降低顺铂诱导的听力降低，组织学研究发现耳蜗听毛细胞损伤明显改善，氧化损伤指标MDA和8-iso-PGF2α含量显著降低。研究结果表明，氢气能通过降低氧化应激对顺铂诱导的耳毒性具有明显改善作用。氢气在降低患者顺铂诱导的耳毒性具有潜在的临床应用价值。

Inhalation of hydrogen gas attenuates cisplatin-induced ototoxicity via reducing oxidative stress

Juan Qu^a, Xu Li^a, Juan Wang^a, Wenjuan Mi^a, Keliang Xie^{b,  ,}  , Jianhua Qiu^{a,  ,  ,} 

Received 26 August 2011; revised 12 October 2011; Accepted 13 October 2011. Available online 3 November 2011.

Conclusion

These results demonstrate that H₂ is beneficial to cisplatin-induced ototoxicity via reducing oxidative stress. Therefore, H₂ has potential for improving the quality of life of patients during chemotherapy by efficiently mitigating the cisplatin ototoxicity.

Abstract

Objective

Cisplatin, an anticancer drug used extensively to treat a broad range of tumors, has strong ototoxic side effects induced by reactive oxygen species (ROS). Recently, it has been reported that hydrogen gas (H₂) is a new antioxidant by selectively reducing hydroxyl radical, the most cytotoxic ROS. The present study was designed to investigate whether H₂ treatment is beneficial to cisplatin-induced ototoxicity via reducing oxidative stress.

Methods

The animals were intraperitoneally given a 30 min infusion of 16 mg/kg cisplatin or the same volume of saline. H₂ treatment was given twice with 2% H₂ inhalation for 60 min starting at 1 h and 6 h after cisplatin or saline injection, respectively. The hearing status of all animals was evaluated by auditory brainstem responses (ABR). The hair cell damage was observed by phalloidin staining. In addition, the levels of oxidative products in serum and cochlear tissue were measured.

Results

We found that H₂ treatment significantly attenuated cisplatin-induced hearing loss evaluated by click-evoked and tone burst ABR threshold. Furthermore, histological analysis revealed that 2% H₂ treatment significantly alleviated cisplatin-induced hair cell damage in the organ of corti. In addition, cisplatin significantly increased the levels of malondialdehyde (MDA) and 8-iso-prostaglandin F2α (8-iso-PGF2α) in serum and cochlear tissue, which was attenuated by H₂ treatment.

Conclusion

These results demonstrate that H₂ is beneficial to cisplatin-induced ototoxicity via reducing oxidative stress. Therefore, H₂ has potential for improving the quality of life of patients during chemotherapy by efficiently mitigating the cisplatin ototoxicity.

Keywords: Cisplatin; Ototoxicity; Hearing loss; Hydrogen gas (H₂); Oxidative stress

Article Outline

1. Introduction

2. Materials and methods

2.1. Animals

2.2. Grouping

2.3. H₂ treatment

2.4. Auditory brainstem responses

2.5. Detection of hair cell damage

2.6. Detection of oxidative products

2.7. Statistical analysis

3. Results

3.1. H₂ treatment attenuated cisplatin-induced hearing loss

3.2. H₂ treatment attenuated cisplatin-induced damage of hair cells

3.3. H₂ treatment attenuated cisplatin-induced oxidative stress in serum and cochlear tissue

4. Discussion

Conflict of interest

Acknowledgements

References