Attenuation of cisplatin ototoxicity by otoprotective effects of nanoencapsulated curcumin and dexamethasone in a guinea pig model.

OBJECTIVES: Cisplatin, one of the most effective and widely used chemotherapeutic agents in the treatment of head and neck malignancies, has severe dose-limiting side effects including ototoxicity. This study evaluates the effectiveness of nanoencapsulated curcumin and dexamethasone in preventing degenerative changes in inner ear cells caused by cisplatin. STUDY DESIGN: Prospective study, animal experiment. METHODS: Cultured auditory cells [House Ear Institute Organ of Corti-1 (HEI-OC1)] and a guinea pig model were used for in vitro and in vivo experiments, respectively. Cell viability assays were conducted to compare the direct toxicity of cisplatin against auditory cells in the presence or absence of pretreatment with nanoencapsulated curcumin and dexamethasone. To recapitulate these effects in vivo, 68 guinea pigs received cisplatin either alone, or along with dexamethasone, nanoencapsulated curcumin, or the combination of both products. Outcome measures included auditory brainstem response, cochlear morphology under both light and scanning electron microscopy, and antioxidant enzyme assays. RESULTS: Pretreatment of auditory cells with naonoencapsulated curcumin and dexamethasone resulted in significant attenuation of cisplatin toxicity. Similarly, in the corresponding animal model (guinea pig), cisplatin caused an average hearing loss of 50 dB, which was attenuated by nanoencapsulated curcumin and dexamethasone across all of the hearing frequencies. There was also greater preservation of histologic structures in this group. Superoxide dismutase and catalase activities were increased in cisplatin-treated animals, whereas the nanoencapsulated curcumin with dexamethasone led to a diminution of this effect. CONCLUSION: Nanoencapsulated curcumin administered in combination with dexamethasone provides a partial but marked protection against cisplatin-induced hearing loss, likely because of reduced toxic damage to auditory cells.

Histopathologic changes in the cochlea associated with diabetes mellitus--a review.

BACKGROUND: The pathologic changes that occur as a result of diabetic microangiopathy have been well described for the kidneys and the eyes. Although many studies suggest an association between diabetes mellitus and hearing loss, the pathologic changes in the cochlea in association with the diabetic state remain to be clarified. AIM/OBJECTIVE: The aim of this review is to determine the effects of diabetes mellitus on cochlear morphology. METHOD: A comprehensive search for relevant articles was carried out on electronic databases of Ovid Medline, Ovid Medline in Process, PubMed, Ovid Embase,or Biosis Preview, The Cochrane Library, ISI Web of Science, and Scopus. Articles published in English between 1940 and June 2010 were eligible to be reviewed. Using predefined inclusion criteria, published articles on histologic changes occurring in the cochlea due to diabetes mellitus were selected and reviewed, and their findings were synthesized. RESULTS: Changes were observed in the basement membrane of the capillaries of the stria vascularis and in the basilar membrane, which was remarkably thickened, giving rise to diabetic microangiopathy. Loss of spiral ganglion neurons, organ of Corti cells, and atrophic changes in the stria vascularis were varied and infrequent. CONCLUSION: There seems to be variable vulnerability of different cochlear cell types to the DM state. Further studies are required to determine the factors responsible for the differences in the histopathologic observations of cochlear tissues.

Auditory risk of hyperbilirubinemia in term newborns: a systematic review.

OBJECTIVES: High levels of unconjugated bilirubin have been associated with neuronal damage. The auditory brain nuclei and the inferior colliculi are often the first part of the brainstem to be involved, often leading to hearing abnormalities. A systematic review of clinical studies was conducted to evaluate the effect of hyperbilirubinemia on hearing in term newborns, to show the relationship between hearing function and bilirubin levels as well as the effect of treatment. METHODS: Eligible studies were identified through searches of electronic databases Ovid MEDLINE, Ovid MEDLINE In-Process, Embase, PubMed and The Cochrane Library. Articles obtained were independently reviewed by 2 authors using inclusion criteria to identify eligible studies. The search was restricted to articles written in English, French and Spanish and published between 1970 and 2010. Data extracted included study type, number of patients, bilirubin levels, hyperbilirubinemia criteria, hearing assessment methods, time of hearing assessment and outcome measures. RESULTS: The nineteen articles included showed heterogeneity regarding the time of hearing test and hyperbilirubinemia criteria. The incidence of hearing loss at initial testing ranged between 13.2-83.3% and 6.7-14.3% at 3 months follow-up. Five studies showed a rising incidence of hearing loss with increasing levels of serum bilirubin. CONCLUSIONS: Hyperbilirubinemia resulted in abnormal hearing assessment in up to 83.3% of term newborns. Greater hearing abnormalities were observed with rising serum bilirubin levels. Treatment of hyperbilirubinemia led to a considerable decrease in the incidence of hearing loss.