Auditory effects of noise pollution: Current research and future trends

Kiran Natarajan; S Sudhamaheswari; Sathiya Murali; Amarnath Devarasetty; Mohan Kameswaran

doi:10.4103/aiao.aiao_3_16

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Year : 2017 | Volume : 1 | Issue : 1 | Page : 2-5

Auditory effects of noise pollution: Current research and future trends

Kiran Natarajan, S Sudhamaheswari, Sathiya Murali, Amarnath Devarasetty, Mohan Kameswaran
Madras ENT Research Foundation, Chennai, Tamil Nadu, India

Date of Web Publication

8-Nov-2017

Correspondence Address:
Kiran Natarajan
Madras ENT Research Foundation, 1, 1^st Cross Street, Off 2^nd Main Road, Raja Annamalaipuram, Chennai - 600 041, Tamil Nadu
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/aiao.aiao_3_16

Abstract

Noise pollution is increasingly being recognized as a major health problem in India. An increased incidence of noise-induced hearing loss (NIHL) has been observed in recent years. Several advances have taken place in the understanding of the molecular basis of NIHL. This can help in evolving preventive and treatment strategies. Research in genetics is progressing at a rapid pace, and several genes linked to NIHL have been identified. In the future, gene therapy may be available as a management modality. This paper will focus on the current research and future trends on the auditory effects of noise pollution.

Keywords: Genetics, molecular mechanisms, noise-induced hearing loss

How to cite this article:
Natarajan K, Sudhamaheswari S, Murali S, Devarasetty A, Kameswaran M. Auditory effects of noise pollution: Current research and future trends. Ann Indian Acad Otorhinolaryngol Head Neck Surg 2017;1:2-5

How to cite this URL:
Natarajan K, Sudhamaheswari S, Murali S, Devarasetty A, Kameswaran M. Auditory effects of noise pollution: Current research and future trends. Ann Indian Acad Otorhinolaryngol Head Neck Surg [serial online] 2017 [cited 2023 Mar 26];1:2-5. Available from: https://www.aiaohns.in/text.asp?2017/1/1/2/217839

Introduction

Noise is disharmonic, unwanted sound and its effects, both auditory and nonauditory, have been largely neglected in most countries, including India. Noise-Induced Hearing Loss (NIHL) can be caused by a one-time exposure to an intense impulse sound or more commonly by a long-term sustained exposure with sound pressure levels (SPLs) in excess of 80–85 dBHL. Noise pollution is now increasingly recognized as a public health problem. The WHO estimates that 10% of the world population is exposed to SPLs that could cause NIHL. Road traffic noise is one of the main sources of noise pollution. The noise levels have been monitored across different parts of the city, and ambient noise levels have been found to be above permissible limits. An increased incidence of NIHL has been observed in the population in recent years, emphasizing the need for increasing efforts to prevent and manage NIHL. This article will highlight the current research and future trends in noise pollution.

Pathophysiology of Noise-Induced Hearing Loss

Besides age-related hearing loss, NIHL is the second most frequent form of hearing loss.^[1] However, noise is one of the major preventable causes of hearing loss. The characteristic pathology of NIHL is the loss of hair cells in the Organ of Corti. Since mammals do not have the ability to regenerate hair cells, NIHL can be irreversible. Outer hair cells (OHCs) are more susceptible to noise exposure than inner hair cells. The basal region of the organ of Corti is more vulnerable to noise injury compared to the low-frequency apical region. The findings in NIHL include the destruction of OHCs, floppy stereocilia, fusion and loss of stereocilia, loss of adjacent supporting cells, complete disruption of the organ of Corti, progressive Wallerian degeneration, and loss of primary auditory nerve fibers.

Significant milestones have been reached in the understanding of the cellular and molecular mechanisms of NIHL which can help in developing therapeutic strategies. Cochlear injury due to excessive noise can occur by mechanical and metabolic mechanisms. With exposures of 115–125 dB SPL at the ear, mechanical damage tends to predominate. However, in most scenarios, the level of noise exposure to the ear is <115 dB, and the damage is metabolically driven.^[2] A complex interplay of genetic and environmental factors leads to oxidative stress at a molecular level. Oxidative stress hypothesis for noise-induced cochlear injury states that acoustic overexposure causes generation of reactive oxygen species (ROS) and reactive nitrogen species which oxidize cell membrane lipids, intracellular proteins, and DNA. Production of pro-inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor α, vasoactive lipid peroxidation products such as isoprostanes leading to reduced cochlear blood flow, excessive release of neurotransmitters such as glutamate, and increase in intracellular calcium occurs. An important component of cochlear microcirculation is the diameter of the spiral modiolar artery, a branch of the anterior inferior cerebellar artery, which meets the lateral cochlear wall to form the stria vascularis. The spiral modiolar artery has been shown to constrict during and after noise exposure.^[3] Glutamate excitotoxicity, GSH depletion, excessive increases in intracellular calcium, and ischemia reperfusion can all lead to mitochondrial injury and have been implicated in noise injury to the cochlea.^[2] Mitochondrial membranes become permeable and release respiratory enzyme molecules (e.g., cytochrome c) that activate cell death effector proteins (e.g., caspases). Programmed cell death pathways involve calpain, caspases, and c-Jun N-terminal kinase Jun molecules. Cochlear antioxidant defenses (antioxidant enzymes, heat shock proteins [Hsps], trophic factors, vitamins C and E, and glutathione [GSH]) are overwhelmed. Both inflammatory and immune responses are central mechanisms in the cochlear defensive response to noise and if unregulated, contribute to hearing loss. Transforming growth factor β (TGF-β) is a key regulator of both responses, and high levels of this factor have been associated with cochlear injury in animal models.

Another new avenue of research in this field has opened yet another dimension– that of genetic predisposition to NIHL. Rick A Friedman identified the Nox3, which is almost exclusively expressed in the inner ear, as a key gene for susceptibility to NIHL.^[4] An increased susceptibility to NIHL may rely on the SNPs of several other genes, including the groups of oxidative stress genes, K + ions recycling genes, monogenic deafness genes, as well as mitochondrial genes.^[5] Another study by Kowalski et al. identified one of the most interesting candidate genes CDH23 encoding Cadherin 23 which is a component of stereocilia tip links in patients with high susceptibility to noise confirming this CDH-23 genetic variant may modify the susceptibility to NIHL development in humans.^[6] Cadherins are calcium-dependent proteins that hold cells together at adherens junctions to form tissues and organs. The cadherin of interest named otocadherin or CDH23 is localized to the stereocilia of the OHCs. Reduction of or missing otocadherin weakens the cell and may allow stereocilia to be more easily physically damaged by loud sounds and by aging.^[7],[8]

Severe noise exposure can induce Hsps, and exposure to moderate noise has been reported to confer protection against noise-induced damage to hearing. Some haplotypes of the hsp70 genes may be associated with a higher susceptibility to NIHL.^[9] In the inner ear, P2X2 receptors are thought to regulate sound transduction and auditory neurotransmission, OHC electromotility, inner ear gap junctions, and K + recycling.^[10] The absence or mutation of P2X2 receptor increases susceptibility to NIHL. Apoptosis may be executed by a family of cysteine proteases called caspases.^[11] X-linked inhibitor of apoptosis suppresses caspase-3 activity and may reduce NIHL. Proteins of the Bcl2 family have been implicated in regulating sensory cell survival and control of apoptotic pathways modulating neuronal cell death, including NIHL.^[12] The Bcl2 family consists of a group of proapoptotic and antiapoptotic molecules that regulate caspase activation. The mechanisms of sensory hair cell degeneration in response to different ototoxic stimuli share a final common pathway: caspase activation. Inhibition of caspases prevents or delays hair cell death and may preserve hearing/balance function. Inhibition of mitogen-activated protein kinases (MAPK) protects against noise-induced hair cell death.^[13] BclxL plays an essential role in the prevention of sensory cell death following TTS levels of noise, and PTS exposure provokes the expression of Bak and with that, cell death.^[12]

Glutathione-S-transferase (GST) enzymes are vital for antioxidant protection. Genetic variability in GST enzymes increases susceptibility to damage from oxidation. It has been suggested that an individual with a null genotype is more likely than his peers to develop NIHL when exposed to excessive noise.^[3] There are also genetic mutations that reduce susceptibility to NIHL. A1555G or other mitochondrial variants in the MTRNR1 and MTTS1 have been suggested as factors that lessen susceptibility to NIHL.^[3] The additional research on the genetic susceptibility to NIHL has focused on human 8-oxoG DNA glycosylase1 (hOGG1), a key enzyme in the human base excision repair pathway. This DNA repair has been shown to be essential in maintaining hearing after noise exposure. The hOGG1 Cys/Cys genotype may have a lesser capacity for restoring 8-oxoG damage, and thus a higher susceptibility for NIHL.^[3]

Atoh1 (also known as math1) has been shown to be essential for neurogenesis in the central and peripheral nervous system, and for the formation of several nonneural cell types. In the auditory system, Atoh1 plays a critical role for hair cell differentiation during development. The hallmark of mechanosensory hair cells is the stereocilia, where mechanical stimuli are converted into electrical signals. While hair cells in lower vertebrates and the mammalian vestibular system can spontaneously regenerate lost stereocilia, mammalian cochlear hair cells no longer retain this capability. Atoh1 may be a gene critical for promoting repair/regeneration of stereocilia and maintaining injured hair cells in the adult mammal cochlea.^[14]

Management of Noise-Induced Hearing Loss

One-third of permanent hearing loss is preventable with proper hearing loss prevention strategies. Hearing protection devices and environmental engineering solutions to abate noise are a critical part of prevention.^[2] Hearing aids and cochlear implants are the currently available management strategies. Considering the oxidative stress hypothesis for NIHL, many different therapeutic approaches may be available for managing NIHL by enhancing the cellular oxidative stress defense pathways in the cochlea.^[15] Antioxidants that have been studied include N-acetylcysteine, magnesium, salicylate, vitamin E and Ebselen.^[16],[17] Glucocorticoid receptors are expressed in the human cochlea. Glucocorticoids, such as cortisol, may modulate hearing sensitivity (Canlon et al. 2007) and also shows some protective effects.^[18] Calcium channel blockers or agents that improve cochlear blood flow are potential treatment modalities. TGF-β is a key regulator of both inflammatory and immune responses. This opens the intriguing possibility of targeting TGF-β as a therapeutic strategy for preventing or ameliorating NIHL.^[19] TGF– b 1 peptidic inhibitors P17 and P144 just before or immediately after noise insult significantly improved hearing thresholds and the degenerative changes in lateral wall structures.^[19] Similarly, another study by Martínez-Vega et al. has shown that long-term omega-3 fatty acid supplementation prevented expression changes in homocysteine metabolism and ameliorates progressive hearing loss in mice.^[20] A mitochondrial metabolite known as acetyl-L-carnitine restore mitochondrial membrane integrity and reduce mitochondrial free radical formation, preventing mitochondrial-induced apoptosis. Cytochrome c release from damaged mitochondria can be prevented by preventing pore formation (e.g., overexpression of Bcl-2 or Bclxl though a gene therapy vector).^[2] Reducing glutamate excitotoxicity include countering the damaging ionic fluxes nonspecifically through magnesium supplementation, or more specifically, through the application of an antagonism of glutamate receptor–associated ionic channels. Maintaining, enhancing, and restoring cochlear GSH levels which is a key intracellular antioxidant and inhibitor of stress-induced apoptosis has several potential advantages as a treatment strategy to reduce NIHL. GSH can counter the harmful effects of glutamate excitotoxicity, mitochondrial injury, and excessive intracellular calcium fluxes. A variety of GSH or cysteine precursors and cell-permeable forms (esters) of GSH such as NAC, methionine, GSH esters, and thiazolidine-related drugs, such as 2-oxothiazolidine-4-carboxylate have been shown to reduce NIHL in laboratory studies.^[2] Other more specific apoptotic pathway inhibitors, for example, leupeptin, a calpain inhibitor, inhibiting steps in the MAPK signaling pathway of apoptosis has been found to be somewhat effective in reducing noise injury to the cochlea. In addition, specific programmed cell death pathway inhibitors (e.g., round window membrane application of c-Jun antisense oligonucleotide therapy or D-JNKI-1 treatment) may prove to be useful clinically.^[2] The olivocochlear system may help protect against acoustic trauma. Sound conditioning involves moderate-level sound exposures daily and may help reduce injury from a subsequent high-level noise exposure.

The ability to initiate auditory sensory cell regeneration through gene therapy to restore NIHL looms in the future. Mammals have not been shown to form new hair cells after injury in mature animals. This may be explained in part by the presence of cell proliferation inhibitors found to be active in the cells of the mature mammalian cochlea. Nevertheless, in the future, it may be possible to override this block on proliferative regeneration through the use of trophic factors alone or in combination with inhibitors of cell proliferation inhibitors. Genes important for the genesis of hair cells in mammals, including Notch, Math 1, Brn3.1 have been discovered.^[2] The possibility of regenerating stereocilia in the noise deafened guinea pig cochlea by cochlear inoculation of a viral vector carrying Atoh1, a gene critical for hair cell differentiation, promoting repair or regeneration of stereocilia and maintaining injured hair cells in the adult mammal cochlea has been explored. Atoh1-based gene therapy, therefore, has the potential to treat noise-induced hearing loss if the treatment is carried out before hair cells die.^[14] Research at Massachusetts Eye and Ear and Harvard Medical School showed that hair cells can be regenerated using a drug which inhibits an enzyme called gamma secretase. This inhibits a signal generated by a protein called Notch on supporting cells. Supporting cells are stimulated to become new hair cells resulting in partial recovery of hearing in mouse ears damaged by noise trauma.^[21]

Conclusion

Noise-induced hearing loss remains a major cause of deafness and a huge public health issue in our country. Insights into the molecular mechanisms of noise-induced cochlear injury may result in the development of new treatment strategies that render the cochlea more resistant to noise as well as enhance the recovery of noise-injured cochleae. Advances in decoding the genetic predisposition for NIHL will facilitate early screening and aid in developing prevention and treatment strategies. Gene therapy may be available in the future to manage noise-induced hearing loss.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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