Antioxidants efficacy in the prevention of sensorineural hearing loss Drd.Buzescu Mdlina Cond.tiinific: Prof.dr.

Draoveanu Constantin Sensorineural hearing losses are auditory impairments caused by pathologic alterations of the inner ear, auditory nerve or auditory cortex. Chronic sensorineural hearing loss is, usually, considered cureless. As consequence, the therapeutic means capable to conserve the function of the inner ear would be the only way to preserve hearing (except hearing aids). As data from the literature prove the implication of reactive oxygen species (ROS) in the pathogenesis of acoustic trauma, ototoxicity and presbicusis, the use of antioxydants in preventing these diseases is a logical approach. An important argument to begin this research was a clinical case of a lady (M.E., 59 years old) with diabetes mellitus and a sensorineural hearing loss of 55,7 dB in average (125 8000 Hz), who received a therapy (600 mg alpha-lipoic acid/day p.o.) for her peripheric neuropathy caused by diabetes. Surprisingly, after 3 months of antioxydant therapy, a new audiogram showed a hearing threshold of 33,4 dB, which means an average improvement of 22,3 dB. The first chapters of the thesis remind some anatomical, physiological and pathophysiological data regarding the inner ear, the auditory cells and the main pathological entities studied: chronic acoustic trauma, ototoxicity and presbicusis. There also is a short presentation of the latest results of research regarding the therapy of sensorineural hearing loss. There are two main directions followed: preservation of the existing auditory hair cells (with antioxidants, inhibitors of intracellular stress pathways that cause apoptosis, inhibitors of the apoptotic mechanism and neurotrophic factors) and generation of new cochlear auditory hair cells (by mitosis from supporting cells, transformation of supporting cells in hair cells and implantation in the cochlea of cells capable to become hair cells stem cells). The present research on sensorineural hearing loss is focused on two main directions: - - Prevalence and correlation of in adulthood acquired sensorineural hearing loss to several risk factors; - Efficacy of antioxydant therapy in the prevention of sensorineural hearing loss . The study group included 981 patients with sensorineural hearing loss, analyzed in a prospective, longitudinal, clinical and statistical research carried on between October 1999 and October 2004. Among this group of patients, 512 were diagnosed with noise induced hearing loss, 154 patients presented ototoxicity and 315 patients had an age related hearing loss (presbycusis). The clinical and complementary investigations performed in this groups of patients included: Anamnesis, ENT clinical examination; Complementary investigations - routine and specific to the diagnosed conditions; Routine pure tone audiometry Self-evaluation hearing questionnaires for elderly Standard pure tone audiometry, vocal audiometry

Establishment of the noise levels in the working environments by a Norsonic NOR 116 sonodosimeter Statistical analysis statistical significance tests (X2, p, t tests), informatically computed with help of Analyse-it (version 1.71 for Microsoft Excel) software. The results of audiometric measurements in the study group leaded to a hearing loss prevalence of 14%, superior to the national mean value of around 10%, due to the fact that the screening was performed on a population with risk factors for hearing loss. According to the present study, the hearing loss is occuring sooner, progresses faster and becomes more important in men than in women, up to the nineth decade of life, when these values become equal. The evaluation of risk factors favoring the occurance of sensorineural hearing loss showed diabetes mellitus (p=0,0046, OR=1,49, RA=33%) and important smoking habits, TI>50 (p=0,046, OR=1,15, RA=13,5%) as statistically significant risk factors for hearing loss. Concerning the risk factors for noise induced hearing loss, we found a statistically very significant influence of age (p< 0,0001, OR = 2,2, RA = 54,8%), and significant influences of high blood pressure (p=0,0083, OR=1,3, RA=23,2% ) and intensive smoking habits (p=0,008, OR=1,28, RA=22,2%). The prevalence of ototoxicity was 19,46% in this study, with the most important hearing loss found for kanamycin. The statistically significant risk factor for ototoxicity was intensive smoking (p=0,0038, OR=1,69, RA=41%). Aspirin (in antiinflamatory dosis) was, in this study, no additive risk factor for ototoxicity, showing a rather protective (not statistically significant) effect on ototoxic exposed cochleas, result confirmed by a recent, complex, chinese study. The prevalence of presbicusis in people over 50 was 33,7% and the significant risk factors for it were previous exposure to noise (p<0,0001, OR=2,48, RA=59,7%) and intensive smoking (p=0,0085, OR=1,65, RA=39,4%). A factor with borderline statistic significance was the male sex (p=0,0496, OR=1,31, RA=23,9%). Further, some recent data on the characters and effects of alpha-lipoic acid are described. The study on the efficacy of antioxidants in prevention of different types of sensorineural hearing loss compared the effects of alpha-lipoic acid, an antioxidant complex composed of vitamin A, C, E and Selenium and placebo. After using previously established specific inclusion and exclusion criteria, there were randomly selected three study groups (A-alpha-lipoic acid, B ACESe and C control) for each of the three types of sensorineural hearing loss (noise induced hearing loss, ototoxicity and presbicusis). The results of this study showed for noise induced hearing loss a statistically significant hearing improvement in the alpha-lipoic acid group, no significant result in the ACESe group and a statistically significant hearing loss in the control group. For ototoxicity, the hearing loss in the alpha-lipoic acid group was significantly lower than in the B and C groups (with no significant difference between these last two). Presbicusis showed a stationary pattern in the two antioxidant treated groups, while in the control group, there was a statistically significant age related hearing loss. The conclusions of the thesis are: - a significant protection by alpha-lipoic acid of the cochlea exposed to noise, with a limited protective effect of the ACESe complex - a significant protection by ALA in ototoxicity and no significant protection of the ACESe complex; - age related hearing loss had no significant progression under antioxidant therapy (ALA or ACESe) but a significant progression in 6 month without any antioxidant protection.