Noise-induced hearing loss in chinchillas pre-treated with glutathione monoethylester and R-PIA1
Introduction
Over the last several years, reactive oxygen species (ROS) have been implicated in many injuries and disease processes (Bolli et al., 1988, Braughler and Hall, 1989, Halliwell and Cross, 1994, Stadtman and Berlett, 1998, Wells et al., 1997). The physiological changes that take place in the ear following noise exposure (i.e., mechanical disruption, ischemia/reperfusion, osmotic changes) may generate ROS (Beagley, 1965, Halliwell and Gutteridge, 1984a, Halliwell and Gutteridge, 1984b, Halliwell and Gutteridge, 1999, Hamernik et al., 1980, Hamernik et al., 1984, Henderson et al., 1974, Spoendlin, 1971, Spoendlin, 1976, Spoendlin and Brun, 1973, Yamane et al., 1995b). ROS activity has been identified within the ear following noise exposure (Liu, 1992, Nicotera et al., 1999, Ohlemiller et al., 1999, Yamane et al., 1995a, Yamane et al., 1995b), and several endogenous antioxidants including glutathione (GSH) (Bobbin and Fallon, 1992, Bolli et al., 1988) and GSH-related enzymes (Jacono et al., 1998) show increased activity after a noise exposure.
If noise-induced ROS activity exceeds the capacity of the antioxidant defense system, then supplying supplemental antioxidants may decrease the effects of ROS damage from intense noise exposures (Hight et al., 1999, Hu et al., 1997, Kopke et al., 2000, Liu et al., 1999, Seidman et al., 1993, Yamasoba et al., 1998a). R-phenylisopropyladenosine (R-PIA) has been shown to increase levels of catalase, superoxide dismutase (SOD), and GSH in vitro and in vivo within the cochlea (Ford et al., 1997, Maggirwar et al., 1994). R-PIA has also been shown to improve blood flow, diminishing the harmful effects of ischemia/reperfusion (Yu et al., 1997, Zhao et al., 1993). Further, R-PIA is a glutamate antagonist and could counter increased levels of glutamate production within the cochlea, thereby decreasing damage from excitotoxicity (Ford et al., 1997, Ramkumar et al., 1994). Previous studies have shown that application of R-PIA directly to the round window prior to noise exposure results in less hearing loss and hair cell loss occurring in the treated ears than in the untreated ears (Hu et al., 1997, Liu et al., 1999).
In order to separate the antioxidant process from other potential physiological changes, the decision was made to deliver a substance that would only upregulate an endogenous antioxidant. The best antioxidant to apply appeared to be GSH, which was found in increased levels in the cochlea following noise exposure (Bobbin and Fallon, 1992, Bobbin et al., 1995). GSH, however, is not easily upregulated, because feedback inhibition during the first phase of GSH synthesis maintains it within tightly controlled levels (Meister and Anderson, 1983, Meister et al., 1986). Additionally, it are the biochemical precursors of GSH which are normally taken up for its intracellular synthesis, rather than GSH itself. It is difficult to increase endogenous levels of GSH by delivering it to the cell. Therefore, the esterified analogues of GSH were determined to be the best method of raising intracellular levels of GSH (Anderson and Meister, 1989, Anderson et al., 1985) prior to the noise exposure. Because glutathione monoethylester (GEE) has a lower toxicity than other esterified analogues (Anderson et al., 1994), it was selected for our experiments. Three concentrations of GEE were used in order to determine if there was a best dose for protection. Since R-PIA had previously been found to be effective in protecting against noise exposure, it was also combined with the GEE to see if there was an additive effect.
Section snippets
Subjects
The subjects were 60 adult chinchillas. There were six groups of 10 animals for the different test conditions. Prior to inclusion in an experimental group, all subjects were evaluated using evoked potentials to determine thresholds for each ear. Each subject had one ear treated, leaving the other ear untreated, so that each subject served as its own control. The decision not to treat the opposite ear with saline was based on previous data (Hu et al., 1997) that showed the 30 μl drop of saline
What dose of GEE provides the most protection from impulse noise?
The first set of experiments explored the effects of three doses of GEE on threshold shifts and hair cell loss caused by impulse noise. Thresholds for the 50 mM GEE group, measured prior to noise exposure and 21 days after the exposure, are shown in Fig. 1. Prior to noise exposure, thresholds of ears assigned to treatment and control conditions were nearly identical. When measured 21 days after exposure, thresholds were significantly elevated compared to pre-exposure values in control ears,
Discussion
R-PIA has been shown to decrease the amount of hearing loss and hair cell loss generated following both impulse and continuous noise exposure (Hu et al., 1997, Liu et al., 1999). R-PIA has several mechanisms that may help to ameliorate the damaging effects of noise. R-PIA upregulates SOD, glutathione peroxidase, catalase, and glutathione reductase, which can be utilized to reduce ROS generated from the exposure (Ford et al., 1997, Maggirwar et al., 1994). As nitric oxide (NO) levels are
Acknowledgements
The authors appreciate the reliable surgery done by X.Y. Zheng and the anatomic assessment done by D. Ding. The experiments were supported by a NIDCD grant (1 P01 DC03600-01A1) to D.H.
References (53)
- et al.
Glutathione monoesters
Anal. Biochem.
(1989) - et al.
Preparation and use of glutathione monoesters
Methods Enzymol.
(1994) - et al.
Glutathione monoethyl ester: preparation, uptake by tissues, and conversion to glutathione
Arch. Biochem. Biophys.
(1985) - et al.
Intense sound increases the level of an unidentified amine found in perilymph
Hear. Res.
(1992) - et al.
Evidence that glutathione is the unidentified amine (Unk 2.5) released by high potassium into cochlear fluids
Hear. Res.
(1995) - et al.
Central nervous system trauma and stroke. I. Biochemical considerations for oxygen radical formation and lipid peroxidation
Free Radic. Biol. Med.
(1989) - et al.
The use of monochlorobimane to determine hepatic GSH levels and synthesis
Anal. Biochem.
(1990) - et al.
Expression and function of adenosine receptors in the chinchilla cochlea
Hear. Res.
(1997) - et al.
Free radicals, lipid peroxidation, and cell damage
Lancet
(1984) - et al.
Lipid peroxidation, oxygen radicals, cell damage, and antioxidant therapy
Lancet
(1984)
Anatomical correlates of impulse noise-induced mechanical damage in the cochlea
Hear. Res.
R-phenylisopropyladenosine attenuates noise-induced hearing loss in the chinchilla
Hear. Res.
Changes in cochlear antioxidant enzyme activity after sound conditioning and noise exposure in the chinchilla
Hear. Res.
Reduction of noise-induced hearing loss using L-NAC and salicylate in the chinchilla
Hear. Res.
Adenosine acts as an endogenous activator of the cellular antioxidant defense system
Biochem. Biophys. Res. Commun.
Age-related decline of auditory function in the chinchilla (Chinchilla laniger)
Hear. Res.
Comparison of psychophysical and evoked-potential tuning curves in the chinchilla
Am. J. Otolaryngol.
Generation of thiol and ascorbyl radicals in the reaction of peroxynitrite with thiols and ascorbate at physiological pH
J. Inorg. Biochem.
Oxidative damage in chemical teratogenesis
Mutat. Res.
Influence of intense sound exposure on glutathione synthesis in the cochlea
Brain Res.
Role of glutathione in protection against noise-induced hearing loss
Brain Res.
Glutathione and glutathione delivery compounds
Adv. Pharmacol.
Acoustic trauma in the guinea pig. II. Electron microscopy including the morphology of cell junctions in the organ of Corti
Acta Otolaryngol.
Demonstration of free radical generation in ‘stunned’ myocardium of intact dogs with the use of the spin trap alpha-phenyl N-tert-butyl nitrone
J. Clin. Invest.
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