Study Of Molecular And Pathological Mechanism Of Protective Effect On Noise-Induced Hearing Loss (NIHL)by Hydrogen-Saturated Saline

Noise-induced hearing loss (NIHL) is a sensorineural hearing deficit thatis mainly caused by a strong noise stimulus. It’s a major cause of occupationaldeafness both in developed and developing countries. It has been estimated thatworldwide as many as500million individuals might be at risk of developingnoise-induced hearing loss (NIHL). Thus, NIHL not only affects health, but is alsoa major social problem. Direct mechanical damage and indirect metabolic damageare recognized as major causes of noise-induced deafness. The excessiveexpression of free radical after noise trauma in the cochlea is recognized as themost important factor causing cochlear damage. Based on this theory, a series ofantioxidant drugs have been used in the study of preventing NIHL. Recent years,studies demonstrated that hydrogen can selectively reduce hydroxyl andperoxynitrite, the most toxic reactive oxygen species, to inhibit oxidative stress,thus acting as an ideal antioxidant reagent. It has been found thathydrogen-saturated medium could significantly reduce the hair cell damagecaused by oxidative stress in vitro. Oral or intraperitoneal induction ofhydrogen-rich saline can also reduce NIHL and hair cell damage in vivo. In thisstudy, the protective effect and specific mechanism of hydrogen on NIHL werestudied by the method of intraperitoneal injection of hydrogen-saturated saline onguineas.Part one Study of the protective effect on noise caused hearing lossby hydrogen-saturated salineThe purpose of the current study was to evaluate hydrogen-saturated saline protecting intensive narrow band noise-induced hearing loss. Guinea pigs weredivided into three groups: hydrogen-saturated saline group; normal saline group;and control group. For saline administration, the guinea pigs were given dailyabdominal injections (1ml/100g)3days before and1h before narrow band noiseexposure (2.5-3.5kHz130dB SPL,1h). The guinea pigs in the control groupreceived no treatment. The hearing function was assessed by the auditorybrainstem response (ABR) and distortion product otoacoustic emission (DPOAE)recording for two weeks. We found that pre-treatment with hydrogen-saturatedsaline significantly reduced noise-induced hearing loss. Our findings suggest thathydrogen-saturated saline is effective in preventing intensive narrow bandnoise-induced hearing loss.Part two Study of the protective effect on noise caused cochlearpathomorphology damage by hydrogen-saturated salineThe purpose of the current study was to evaluate hydrogen-saturated salineprotecting intensive narrow band noise-induced tissue damage of the cochlear.Guinea pigs were also divided into three groups as part one. The tissue damage ofthe cochlear were detected before and14days after noise exposure. By AgNO3staining, scanning electron microscopy, succinate dehydrogenase staining andimmunohistochemical staining, we found that the function and morphology of thehair cell, especially the stereocilia damage of the hydrogen-saturated saline groupwere significantly better than those of the normal saline group. The resultindicated that pre-treatment with hydrogen-saturated saline significantly reducednoise-induced cochlear damage. Part three Study of the molecular mechanism of protective effecton noise-induced hearing loss by hydrogen-saturated salineIn order to explore the protective mechanism of the hydrogen-saturatedsaline, the changes of free radicals, cytokines and related proteins in the cochleabefore noise exposure, and immediately and7days after noise exposure wereexamined. We found that the cytotoxic free radicals (malondialdehyde, lipidperoxidation, and hydroxyl levels), biomarker of oxidative DNA damage(8-OHdG) and inflammatory mediators (IL-1, IL-6, TNF-αand ICAM-1) weresignificantly lower in the hydrogen-saturated saline group after noise exposure.Expression of phosphorylated-p38MAPK was significantly increased in thecochlear of guinea pigs after noise exposure. But the expression ofphosphorylated-p38MAPK of hydrogen-saturated saline group was significantlyhigher than those of normal saline group immediately after noise exposure. Ourfindings suggest that on the one hand, hydrogen-saturated saline can decrease theamount of cytotoxic free radicals and harmful cytokines, on the other hand, it canregulate the phosphorylation of P38MAPK and affect its downstream signalingpathways to prevent the cochlear damage caused by noise trauma.