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Curcuma Longa (Curcumin) Decreases In Vivo Cisplatin-Induced Ototoxicity Through Heme Oxygenase-1 Induction

Fetoni, Anna R.; Eramo, Sara L. M.; Paciello, Fabiola; Rolesi, Rolando; Podda, Maria Vittoria; Troiani, Diana; Paludetti, Gaetano

doi: 10.1097/MAO.0000000000000302
Basic Science

Hypothesis: To investigate whether curcumin may have in vivo protective effects against cisplatin ototoxicity by its direct scavenger activity and/or by curcumin-mediated upregulation of HO-1.

Background: Cisplatin-induced ototoxicity is a major dose-limiting side effect in anticancer chemotherapy. A protective approach to decrease cisplatin ototoxicity without compromising its therapeutic efficacy remains a critical goal for anticancer therapy. Recent evidences indicate that curcumin exhibits antioxidant, anti-inflammatory, and chemosensitizer activities.

Methods: In male adult Wistar rats, a curcumin dose of 200 mg/kg, selected from a dose-response curve, was injected 1 hour before cisplatin administration and once daily for the following 3 days. A single dose of cisplatin (16 mg/kg) was administered intraperitoneally. Rats were divided as follows: 1) control, 2) curcumin control, 3) vehicle control, 4) cisplatin, 5) cisplatin+ vehicle, and 6) curcumin+cisplatin. ABRs were measured before and at Days 3 and 5 after cisplatin administration. Rhodamine-phalloidin staining, 4-hydroxy-2-nonenal and heme-oxigenase-1 immunostainings, and Western blot analyses were performed to assess and quantify OHC loss, lipid peroxidation, and the endogenous response to cisplatin-induced damage and to curcumin protection.

Results: Curcumin treatment attenuated hearing loss induced by cisplatin, increased OHC survival, decreased 4-HNE expression, and increased HO-1 expression.

Conclusion: This preclinical study demonstrates that systemic curcumin attenuates ototoxicity and provides molecular evidence for a role of HO-1 as an additional mediator in attenuating cisplatin-induced damage.

Department of Otolaryngology, Head and Neck Surgery; Institute of Human Physiology, Catholic University of Rome, Rome, Italy

Address correspondence and reprint requests to Diana Troiani, M.D., Institute of Human Physiology, Catholic University of Rome, Largo F Vito, 1, 00168 Rome, Italy; E-mail: d.troiani@rm.unicatt.it

The confocal analysis has been performed at Labcemi, UCSC, Rome. The authors disclose any conflict of interest. This work was supported by “Fondi di Ateneo” from the Catholic University of Rome (to A. R. F. and D. T.) and by the National grant (PRIN) sponsored by Italian Department for Research (MIUR).

Copyright © 2014 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company