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Cascella, Vincenza (2012) STUDIO DEL DANNO UDITIVO CAUSATO DA RUMORE O DA CISPLATINO: EFFETTO PROTETTIVO DI ACUVAL400 ED N-QTER. Tesi di Dottorato , Università degli studi di Ferrara.

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    Hearing is one of the key functions in communication, making us capable to develop our ability to interact with others. The partial or total loss of this function leads to deafness causing significant social problems. Hearing impairment is called hypoacusis and is one of the most common pathologies in our society. Its prevalence varies from about 0.2% in children under 5 years of age to more than 40% in adults over 75 years. Several factors are responsible for hearing loss through oxidative stress, the process by which the cochlear hair cells and neuronal cells of spiral ganglion go toward apoptosis or necrosis (sensorineural hypoacusis). Recently, there have been elucidated many aspects of mechanical and metabolic damage induced by noise (noise-induced hearing loss, NIHL) and by treatment with a potent chemotherapy drug, cisplatin (CDDP). The ototoxicity induced by noise exposure and use of CDDP is characterised by sensory hair cell death subsequent to overproduction of reactive oxygen species (ROS) (super-oxide anion, hydrogen peroxide, hydroxyl radicals), responsible of lipid peroxidation, protein and DNA damage. In particular, the accumulation of ROS determines an increment or a modulation of the activity of endogenous antioxidant enzymes such as glutathione (GSH) and superoxide dismutase (SOD). Several studies report that by increasing the levels of antioxidants (for example through the use of drugs or genetic manipulation) it is possible to promote survival of sensory hair cells and to protect them from acoustic trauma and ototoxic agents. Various papers report the use of different antioxidants (vitamins A, C, E, polyphenols, flavonoids and organosulfur compounds) to treat either noise- or CDDP-induced hearing loss, due to their ability to reduce oxidative stress. Recent studies show how coenzyme Q10 (CoQ10), or ubiquinone, besides being an electron carrier in the complexes I, II and III of the mitochondrial respiratory chain, is an ubiquitous scavenger of free radicals, capable of preventing cochlear lipid peroxidation caused by acoustic trauma and treatment with CDDP. CoQ10 is particularly liposoluble therefore very difficult to be absorbed, so recently it has been developed in a new soluble form, terclatrate CoQ10 (n-QTER). Fetoni et al. used n-QTER and discovered that it could protect sensory cells from apoptosis. Conklin et al. demonstrated how the CoQ10 is able to suppress the lipid-peroxidation, because it is able to increase GSH and SOD levels. Based on the antioxidant properties of CoQ10, we hypothesized that this molecule may protect the cochlea from acoustic trauma and from ototoxicity of CDDP. In particular, it was evaluated the effect of an antioxidant dietary supplement, ACUVAL ® 400, which contains n-QTER (0.32 mg) and an extract of Ginkgo biloba (Ginkgoselect ®), both known for their functions of radical scavenging as well as many other healing properties. From the data analysis obtained by administering different concentrations of n-QTER at different times, before and after the damage induced by noise and by CDDP, it was found that in both cases the protective effect was achieved with an additional dose of n-QTER (500 mg/ kg) in the ACUVAL ® 400 (100 mg/kg).

    Tipologia del documento:Tesi di Dottorato (Tesi di Dottorato)
    Data:3 Aprile 2012
    Relatore:Granieri, Enrico
    Coordinatore ciclo:Capitani, Silvano
    Istituzione:Università degli studi di Ferrara
    Dottorato:XXIV Anno 2009 > SCIENZE BIOMEDICHE
    Struttura:Dipartimento > Morfologia, chirurgia e medicina sperimentale
    Soggetti:Area 06 - Scienze mediche > MED/32 Audiologia
    Parole chiave:cisplatino, coenzima Q10, rumore, sordità, cisplatin, coenzime Q10, noise, deafness
    Depositato il:13 Feb 2013 15:10


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