allopurinol and Hearing-Loss--Noise-Induced

Noise-induced hearing loss (NIHL) is the leading occupational disease and a major contributor to the development of age-related hearing loss. The pharmacological prevention and treatment of NIHL has been under preclinical investigation for the past 20 years. Promising treatments have now been identified and entered into clinical development. Within the next five years, safe and effective drugs could be approved as the first generation of otoprotectants. This review covers strategies that are under investigation for NIHL. Drugs that effectively prevent and treat NIHL will have a significant impact on medical costs, disability compensation and several issues affecting the quality of life.

Topics: Acetylcysteine; Allopurinol; Azoles; Glutathione Peroxidase; Hearing Loss, Noise-Induced; Humans; Isoindoles; Magnesium; Noise, Occupational; Organoselenium Compounds

Temporary threshold shift (TTS) and permanent threshold shift (PTS) may follow prolonged noise exposure. Several reports suggest that noise-induced damage to the cochlea may be related to the activity of reactive oxygen species (ROS). Drugs that scavenge or block ROS formation also protect the cochlea. Guinea pigs, treated with allopurinol, were exposed to white noise (120 dB SPL) or impulse noise (114 dB SPL) for 2 and 5 h. The protective effect of allopurinol was confirmed, but, at these levels of sound, it was present only after noise exposure up to 2 h. This study also offers evidence suggesting that allopurinol does not influence the establishment of PTS.

Topics: Allopurinol; Animals; Auditory Threshold; Evoked Potentials, Auditory, Brain Stem; Female; Free Radical Scavengers; Guinea Pigs; Hearing Loss, Noise-Induced; Time Factors

To investigate the protective effect of two anti-reactive oxygen species (ROS) substances, copper-zinc superoxide dismutase (CuZn-SOD) and allopurinol, in impulse noise-exposed guinea pigs.. Allopurinol or CuZn-SOD were administered intraperitoneally before exposure to 125 dB SPL noise centered at 2.0-3.0 kHz, with a repetition rate of 4/s, for 1.8 h. Hearing thresholds were tested by means of electrocochleography after implanting the animals with permanent electrodes. The presence of lipoperoxides in the guinea pig cochleae exposed to noise-induced oxidative stress was determined by means of the dosage of malondialdhyde, evaluated by measuring the content of thiobarbituric acid reactive substances in perilymph samples.. Acoustic stress induced ROS formation and both allopurinol and CuZn-SOD exerted a protective effect on the cochlea. Comparison of compound action potential thresholds in different animal groups showed that the temporary threshold shift was significantly lower in treated animals than in those without pharmacological protection.. The protective effect of the antioxidant agents demonstrates that, even at a high level of impulse noise exposure, a metabolic mechanism of cochlear damage may still play an important role in noise-exposed sensorineural hearing loss.

Topics: Allopurinol; Animals; Auditory Threshold; Cochlea; Evoked Potentials, Auditory, Brain Stem; Free Radical Scavengers; Guinea Pigs; Hearing Loss, Noise-Induced; Lipid Peroxides; Malondialdehyde; Noise; Oxidative Stress; Perilymph; Superoxide Dismutase; Thiobarbiturates

Free oxygen radicals cause particularly severe tissues and organ damage. They appear to play an important role in the cochlea, mediating noise-exposure damage. In the present study 16 guinea pigs were implanted with permanent electrodes to record cochlear action potential. Eight animals were exposed to a 2-3 kHz, 125 dB SPL noise pulse, at a rate of 4 stimulations per second for 1.8 hours. Prior to noise exposure four out of eight animals were treated with a known dose of allopurinol. The remaining eight animals were used as controls. Endolymphatic malondialdehyde concentration was used as indicator of the lipid peroxidization processes exerted by the free radicals. No significant difference was found between the variations in hearing threshold and malondialdehyde concentration in the animals treated with allopurinol and then exposed to noise vs. the control group. The electophysiological and biochemical results have, therefore, demonstrated that preventative administration of allopurinol can provide valid protection vs. noise impulse damage.

Topics: Allopurinol; Animals; Free Radical Scavengers; Guinea Pigs; Hearing Loss, Noise-Induced

Several studies have demonstrated that noise exposure may result in local vasoconstriction of cochlear vessels. The subsequent decrease in cochlear blood flow may lead to hypoxia and predispose to the formation of free oxygen radicals (FORs). If hypoxia occurs in response to noise exposure, then drugs that scavenge or block the formation of FORs should protect the cochlea from damage resulting from hypoxic or ischemic events as well as noise trauma. Rats were exposed to 60 hours of continuous broad-band noise (90 dB SPL) and treated with superoxide dismutase-polyethylene glycol (SOD-PEG), allopurinol, or a control vehicle. Exposure to noise resulted in significant threshold shifts at each frequency tested (3, 8, 12, and 18 kHz) as measured by tone burst-evoked compound action potentials and cochlear microphonics recorded from the round window. Both of these thresholds in drug-treated animals were attenuated compared with animals exposed to noise alone. These findings show that SOD-PEG and allopurinol may preserve cochlear sensitivity associated with noise exposure. This suggests that noise-induced damage to the cochlea may be related to the activity of FORs.

Topics: Action Potentials; Allopurinol; Analysis of Variance; Animals; Cochlea; Cochlear Microphonic Potentials; Hearing Loss, Noise-Induced; Male; Noise; Rats; Rats, Inbred WKY; Superoxide Dismutase

Dipyridamol has in addition to a coronardilatating effect an ati-thrombotic one too. Moreover it facilitates the release of O2 from haemoglobin by increase of the concentration of 2,3-diphosphoglycerate in the erythrocytes. Allopurinol causes a potential resynthesis of ATP in the cells by inhibition of the metabolism of uric acid. Both substances therefore seemed to be suitable for a medicamental therapy of the noise-induced cochlear damage. The expected favourable effect of Dipyridamol and Allopurinol on the organ of Corti after sound exposure (RMP-measurement before and after exposure to pure tone 120 dB SPL) however had not been confirmed by experiment on animals (guinea pig).

Topics: Allopurinol; Cochlea; Diphosphoglyceric Acids; Dipyridamole; Erythrocytes; Hearing Loss, Noise-Induced; Humans