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

Abstract

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.

Ouabain Does Not Induce Selective Spiral Ganglion Cell Degeneration in Guinea Pigs

“…The denervatory effect of ouabain was originally observed in the cochlea of Mongolian gerbils by Schmiedt and coworkers [ 8 , 9 ] and corroborated by other authors [ 14 – 16 ]. It was subsequently demonstrated to occur as well in the cochlea of other rodent species, such as mouse [ 17 – 22 ] and rat [ 23 – 25 ], mostly in a dose-dependent way.…”

Protective effect of hydrogen-rich medium against high glucose-induced apoptosis of Schwann cells in vitro

“…Numerous clinical studies have demonstrated that H 2 or HS exhibit antioxidative (9,11,12,38), anti-apoptotic (10) and anti-inflammatory (14,15) effects in several disease models. The protective effects of H 2 or HS on zymosan-induced organ impairment (14), lipopolysaccharide (LPS)-associated lung injuries (39), LPS-associated sepsis (15,38,40) and ouabain-induced auditory neuropathy (41) have also been observed in vivo. The results of the present study indicated that HM significantly inhibited oxidative damage in the SCs by selectively suppressing the production of ONOOand OH -, formation of 8-OHdG and activation of PARP-1, leading to a reduction in SC apoptosis via the caspase-independent and caspase-dependent pathways.…”

The hydrogen molecule as antioxidant therapy: clinical application in hemodialysis and perspectives

“…Thereafter, accumulating evidence from animal studies indicated a protective effect of H 2 pretreatment on the progression of organ damage in various types of disease models , such as ischemia-induced injury and dysfunction of the brain [22,33,39,55,59,[62][63][64], heart [34,45,59,65], liver [30], retina [41], and kidney [59,60]; stress-induced hippocampus dysfunction [38]; cisplatinum nephropathy [37,44]; transplanted intestinal graft [31,47]; corneal alkali burn [51]; ouabain-induced auditory neuropathy [66]; lung injury by oxygen toxicity [43,46]; paraquat [52]; extensive burns [54]; chronic allograft nephropathy [48]; and radiation injuries in various organs [49,50,55,68,69]. In Parkinson's disease [36,40] and Alzheimer's disease models [42], H 2 ameliorates neurodegenerative changes in the brain.…”

“…In previous studies, H 2 was administered by inhalation [22,30,31,34,37,45,46,56,[62][63][64]66] or dissolved in water [22, 32-44, 47-55, 57-61, 65, 67-69]. Irrespective of the administration route, H 2 pretreatment could suppress oxidation, inflammation, and apoptosis while enhancing antioxidant reactions in those models.…”