title: Curcuma longa (curcumin) decreases in vivo cisplatin-induced ototoxicity through heme oxygenase-1 induction.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery; Institute of Human Physiology, Catholic University of Rome, Rome, Italy.
authors.forename: Anna R
authors.initials: AR
authors.lastname: Fetoni
authors.forename: Sara L M
authors.initials: SL
authors.lastname: Eramo
authors.forename: Fabiola
authors.initials: F
authors.lastname: Paciello
authors.forename: Rolando
authors.initials: R
authors.lastname: Rolesi
authors.forename: Maria Vittoria
authors.initials: MV
authors.lastname: Podda
authors.forename: Diana
authors.initials: D
authors.lastname: Troiani
authors.forename: Gaetano
authors.initials: G
authors.lastname: Paludetti
mesh_terms: D000818:Animals; D002945:Cisplatin; D003474:Curcumin / Q000494:pharmacology / Q000627:therapeutic use*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects*; D034381:Hearing Loss / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D051547:Heme Oxygenase-1; D003474:Curcumin; D002945:Cisplatin