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

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 (H(2)) is a new antioxidant by selectively reducing hydroxyl radical, the most cytotoxic ROS. The present study was designed to investigate whether H(2) treatment is beneficial to cisplatin-induced ototoxicity via reducing oxidative stress. The animals were intraperitoneally given a 30 min infusion of 16 mg/kg cisplatin or the same volume of saline. H(2) treatment was given twice with 2% H(2) inhalation for 60 min starting at 1h and 6h 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. We found that H(2) treatment significantly attenuated cisplatin-induced hearing loss evaluated by click-evoked and tone burst ABR threshold. Furthermore, histological analysis revealed that 2% H(2) 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 H(2) treatment. These results demonstrate that H(2) is beneficial to cisplatin-induced ototoxicity via reducing oxidative stress. Therefore, H(2) has potential for improving the quality of life of patients during chemotherapy by efficiently mitigating the cisplatin ototoxicity.

Inhalation of hydrogen gas attenuates ouabain-induced auditory neuropathy in gerbils

Aim: Auditory neuropathy (AN) is a hearing disorder characterized by abnormal auditory nerve function with preservation of normal cochlear hair cells. This study was designed to investigate whether treatment with molecular hydrogen (H(2)), which can remedy damage in various organs via reducing oxidative stress, inflammation and apoptosis, is beneficial to ouabain-induced AN in gerbils. Methods: AN model was made by local application of ouabain (1 mmol/L, 20 mL) to the round window membrane in male Mongolian gerbils. H(2) treatment was given twice by exposing the animals to H(2) (1%, 2%, and 4%) for 60 min at 1 h and 6 h after ouabain application. Before and 7 d after ouabain application, the hearing status of the animals was evaluated using the auditory brainstem response (ABR) approach, the hear cell function was evaluated with distortion product otoacoustic emissions (DPOAE). Seven days after ouabain application, the changes in the cochleae, especially the spiral ganglion neurons (SGNs), were morphologically studied. TUNEL staining and immunofluorescent staining for activated caspase-3 were used to assess the apoptosis of SGNs. Results: Treatment with H(2) (2% and 4%) markedly attenuated the click and tone burst-evoked ABR threshold shift at 4, 8, and 16 kHz in ouabain-exposed animals. Neither local ouabain application, nor H(2) treatment changed the amplitude of DPOAE at 4, 8, and 16 kHz. Morphological study showed that treatment with H(2) (2%) significantly alleviated SGN damage and attenuated the loss of SGN density for each turn of cochlea in ouabain-exposed animals. Furthermore, ouabain caused significantly higher numbers of apoptotic SGNs in the cochlea, which was significantly attenuated by the H(2) treatment. However, ouabain did not change the morphology of cochlear hair cells. Conclusion: The results demonstrate that H(2) treatment is beneficial to ouabain-induced AN via reducing apoptosis. Thus, H(2) might be a potential agent for treating hearing impairment in AN patients.