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


METHODS
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.


CONCLUSIONS
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.
*McGill Auditory Sciences Laboratory, †Montreal Children's Hospital Research Institute, Cancer and Angiogenesis Laboratory, McGill University; and ‡Department of Otolaryngology, The Montreal Children's Hospital, Montreal, Quebec, Canada.
Pezhman
P
Salehi
Olubunmi Victoria
OV
Akinpelu
Sofia
S
Waissbluth
Emilia
E
Peleva
Brian
B
Meehan
Janusz
J
Rak
Sam J
SJ
Daniel
D000818:Animals; D000970:Antineoplastic Agents; D002460:Cell Line; D002945:Cisplatin; D003051:Cochlea / Q000187:drug effects* / Q000473:pathology; D003474:Curcumin / Q000627:therapeutic use*; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects*; D005260:Female; D006168:Guinea Pigs; D006309:Hearing / Q000187:drug effects; D034381:Hearing Loss / Q000188:drug therapy* / Q000473:pathology; D009925:Organ of Corti / Q000187:drug effects / Q000473:pathology; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D003907:Dexamethasone; D003474:Curcumin; D002945:Cisplatin