184.108.40.206. Biological processes involved in noise effects
Many research studies have been performed over more than 50
years to understand physiological dysfunctions induced by
excessive noise exposure.
Over the last five years or so, new and promising data have
uncovered several series of factors having a determinant role.
The main results are presented below, schematically divided into
In some circumstances an acquired resistance to
noise exposure can happen.
Exposure to a previous non traumatizing
sound may prevent acoustic
trauma by a later noise exposure this is known as sound
conditioning (Canlon et al. 1988). Liu et al. (2000) further
extended earlier findings by showing that
sounds could protect from low and middle frequency noise damage.
Niu and Canlon (2002) revealed an up-regulation of
neurotransmitter release in
cochlear efferents in the
process of sound conditioning. Cochlear toughening refers to the
increased resistance happening over repeated noise exposure in
some conditions, in recent experiments Hamernik et al. (2003)
further characterized acoustic parameters influencing this
The very long term effects of
noise as possibly emerging
only at an old age have received contradictory support from
several epidemiologic studies (Ferrite and Santana 2005, Lee et
al. 2005, Rosenhall 2003, Gates et al. 2000). Very recent
experimental data (Kujawa and Liberman 2006) suggest that early
noise exposure can render the
inner ear more
vulnerable to aging.
Unnoticeable effects can also occur over years as indicated by
small instabilities in
cochlear functioning which
were observed in students exposed to noise in their
leisure-times (Rosanowski et al. 2006).
During the post noise
exposure period the presence of loud sounds influences the
amount of recovery. Very few studies were devoted to these
influences the effective parameters of which are poorly known
(Niu et al. 2004, Norena and Eggermont 2005). The beneficial
effects of these post-trauma
environmental sounds can
be quite large and as they are easy to control in humans they
have very high potential clinical implications. Epidemiologic
data also point to similar significant effects in humans (Abbate
et al. 2005).
Environmental factors other than acoustics
Exposure to several chemicals and lowered levels of breathed
oxygen were found to increase NIHL. It was observed that
chemical asphyxiants potentiated NIHL (Fechter et al. 2000) such
as Hydrogen cyanide (Fechter et al. 2002), acrylonitrile (one of
the 50 most commonly produced industrial chemicals) (Fechter et
al. 2003). Hypoxia, the low oxygen breathing, was found to
extend NIHL to all
frequencies above those of
the noise (Chen and Liu
2005). Smoking was also found a significant risk factor
potentiating NIHL in epidemiologic surveys (Burr et al. 2005,
Ferrite and Santana 2005, Wild et al. 2005).
Efferent and sympathetic innervations
The efferent and sympathetic innervations of the
cochlea (a retrocontrol
from the brain to the cochlea) seem to have almost no influence
upon the normal functioning of the cochlea as their suppression
does not lead to noticeable changes. However, they do influence
cochlear reactivity in
adverse conditions, and this has been particularly well observed
with NIHL. A protective role of the efferent system upon NHIL
was uncovered many years ago (Cody and Johnstone 1982). Over the
last years significant progress was made regarding exposure
parameters leading or not leading to protection (Rajan 2001,
Rajan 2003). The predictive value of an efferent response to
assess susceptibility to NHIL remains controversial (Maison et
al. 2002, Luebke et Foster 2002, Wagner et al. 2005), its
involvement in sound
conditioning was shown by Niu and Canlon (2002). An influence of
the sympathetic cochlear innervation on NIHL was uncovered
several years ago (Borg 1982), and later studied. Some
experiments (Horner et al. 2001, Giraudet et al. 2002) further
extended such observations and pointed to an interaction with
the efferent innervation, they also showed modification of
cochlear sensitivity to acoustic trauma by anaesthesia or even
Several newly tested drugs have been proven experimentally to
provide protective or reparative properties with regard to NIHL.
The pharmacological actions of the drugs are only partly known
and many have several metabolic effects and it is difficult to
know which of its metabolic properties is involved in NIHL.
While recognizing this complexity it is fruitful both for
presentation and reasoning to use main pharmacologic categories.
Thus drugs are presented here below into five main categories.
Both steroidal and non steroidal
were found to provide protection against NIHL. Salicylate was
found to facilitate recovery from acoustic trauma (Yu et al.
1999), in a later study salicylate in combination with trolox
(an anti-NOoxidant) it was shown to decrease NIHL (Yamashita et
al. 2005). Corticoids when combined with hyperbaric oxygenation
were shown to provide rescue post-trauma in animal experiments
(d’Aldin et al. 1999, Lamm and Arnold 1999), this was confirmed
and extended by experiments last year in our group (Fakhry et
al. 2007. A role of stress and corticosterone in protecting
against NIHL was observed (Wang and Liberman 2002). Three recent
studies indicate the beneficial action of dexamethasone on NIHL
(Takemura et al. 2004, Tahera et al. 2006, Sendowski et al.
2006a) the last publication comes from a laboratory involved in
Over the last three years about twenty publications documented
the protective effects of drugs with anti-oxidant properties
upon NIHL. These drugs are further somehow differentiated by the
authors with regards to their anti-ROS or anti-NOS properties,
drugs of both classes were found effective. Approximately 12
different drugs were tested. Some were found repeatedly
protective: - N-acetylcysteine (Ohinata et al. 2003, Duan et al.
2004, Kopke et al. 2005), - allopurinol (Franze et al. 2003,
Cassandro et al. 2003), - ebselen (Pourbakht and Yamasoba 2003,
Lynch et al. 2004), - edaravone (Takemoto et al. 2004, Tanaka et
al. 2005) among these at least two are already clinically
accepted drugs at least in some countries. Other drugs already
clinically accepted as salicylate,
vitamin c or vitamin e were
also found protective.
Once NIHL cochlear
damage has started as through
oxidative or other processes apoptotic processes can be
triggered and lead to sensory and neural cochlear cell
disparition. Five different drugs were reported to be protective
aginst NIHL : riluzole (Wang et al. 2002), a peptide inhibitor
of c-Jun N-terminal kinase (Wang et al. 2003), calcineurin
inhibitors (Minami et al. 2004), all-trans retinoic acid, an
active metabolite of
vitamin a (Ahn et al. 2005)
and, Src-PTK inhibitors (Harris et al. 2005). The potential use
of these drugs seems far away at present because of high dose
levels needed and low bioavailability with clinical routes of
Administration of several neurotrophic factors was found
protective against NIHL: - ciliary neurotrophic factor (Zhou et
al. 1999), - GDNF and/or NT3 (Yang et al. 2001, Chen et al.
2002), basic fibroblast growth factor (Zhai et al. 2002, Zhai et
al. 2004). Modulators of neurotransmission were also found
protective: noradrenergic related compounds (Horner et al. 1998,
Giraudet et al. 2002), and NMDA blocking agents (Chen et al.
2003, Diao et al. 2005, Ruel et al. 2005).
Hypothermia (Henry 2003), prior heat acclimatation (Paz et al.
2004) and a heat shock protein inducer (Mikuriya et al. 2005)
were reported to protect from NIHL, as were also ATP (Sugahara
et al. 2004), NO inhibitors (Xiong et al. 2002, Ohinata et al.
2003) and a calcium pump activator (Liu et al. 2002). A special
reference must be made to magnesium treatment which was found
repeatedly protective (Scheibe et al. 2001, Scheibe et al 2002,
Haupt et al. 2003, Attias et al. 2003 , Sendowski et al.