顺铂是以二价铂同两个氯原子和两个氨分子结合的重金属络合物，类似于双功能烷化剂，可抑制DNA的复制过程。DDP细胞最敏感，高浓度时抑制RNA及蛋白质合成。本品对乏氧细胞作用，进入人体后可扩散通过带电的细胞膜。目前认为，DDP主要作用部位在DNA的嘌呤和嘧啶碱基。作用与用途：本品属细胞周期非特异性药物，具有细胞毒性，可抑制癌细胞的DNA复制过程，并损伤其细胞膜上结构，有较强的广谱抗癌作用。临床用于卵巢癌、前列腺癌、睾丸癌、肺癌、鼻咽癌、食道癌、恶性淋巴瘤、头颈部鳞癌、甲状腺癌及成骨肉瘤等多种实体肿瘤均能显示疗效。

顺铂是临床常用的化疗药物之一，具有抗癌谱广、疗效确切等特点，但其副作用大。如何减少这种药物的副作用一直是学术上十分关心的问题。氢气选择性抗氧化效应后不久，就有学者考虑到这个问题，因为顺铂的毒性作用核心问题就是氧化损伤或者自由基增加，那么氢气能减少这种药物的毒性在逻辑上就十分自然了。但是研究这个问题必须考虑到，一是这种保护作用是否明确，另一个重要问题是会不会影响肿瘤治疗效果。由于顺铂最常见的毒性作用表现在肾脏，所以最早研究这个问题的学者就针对这个问题开展，已经证明氢气不影响化疗药物治疗肿瘤的效果，并可以降低其肾脏毒性。

最新研究是针对顺铂的耳毒性，关于耳损伤，比较常用的方式有噪声和庆大霉素诱导，上海长海医院周义德教授和北京301医院于宁教授分别证明氢水能对抗噪声性耳聋。也属于该研究的前期线索，说明氢气对耳损伤具有保护作用。

本研究采用体外耳蜗培养，证明氢气溶解于培养基能有效对抗顺铂的耳毒性，下一步需要用动物模型证明是否具有同样效应，然后应该开展临床研究，确定氢气是否能对抗肿瘤化疗引起耳损伤。

许多患者在进行治疗过早期都会有一定信心，影响这种信心的重要因素是治疗，如果因为治疗导致身体无法耐受，患者可能会对自己身体缺乏足够信心。本来肿瘤本身并没有那么可怕，患者会想到竟然治疗都不能继续，治疗的严重副作用有时候成为患者快速死亡的主要诱因。氢气对肿瘤治疗如放射和化学药物治疗的副作用，应该成为氢气临床医学研究的重点。如果在不影响肿瘤治疗效果的基础上减少副作用，将使患者能坚持更长时间的治疗，这对于建立患者战胜疾病的信心十分重要。

NeurosciLett. 2014 Jul 23. pii: S0304-3940(14)00598-9. doi:10.1016/j.neulet.2014.07.025. Hydrogen protects auditory hair cells fromcisplatin-induced free radicals.

KikkawaYS1, Nakagawa T2, Taniguchi M3, Ito J3.

1Departmentof Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, KyotoUniversity, Kyoto, Japan; Department of Otolaryngology-Head and Neck Surgery,Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Cisplatinis a widely used chemotherapeutic agent for the treatment of variousmalignancies. However, its maximum dose is often limited by severe ototoxicity.Cisplatin ototoxicity may require the production of reactive oxygen species(ROS) in the inner ear by activating enzymes specific to the cochlea. Molecularhydrogen was recently established as an antioxidant that selectively reducesROS, and has been reported to protect the central nervous system, liver, kidneyand cochlea from oxidative stress. The purpose of this study was to evaluatethe potential of molecular hydrogen to protect cochleae against cisplatin. Wecultured mouse cochlear explants in medium containing various concentrations ofcisplatin and examined the effects of hydrogen gas dissolved directly into themedia. Following 48-h incubation, the presence of intact auditory hair cellswas assayed by phalloidin staining. Cisplatin caused hair cell loss in adose-dependent manner, whereas the addition of hydrogen gas significantlyincreased the numbers of remaining auditory hair cells. Additionally,hydroxyphenyl fluorescein (HPF) staining of the spiral ganglion showed thatformation of hydroxyl radicals was successfully reduced in hydrogen-treated cochleae.These data suggest that molecular hydrogen can protect auditory tissues againstcisplatin toxicity, thus providing an additional strategy to protect againstdrug-induced inner ear damage.