The effectiveness of eugenol against cisplatin-induced ototoxicity

Braz J Otorhinolaryngol. Nov-Dec 2019;85(6):766-773. doi: 10.1016/j.bjorl.2018.07.007. Epub 2018 Aug 7.


Introduction: Ototoxicity refers to cellular damage or function impairment developing in the inner ear in association with any therapeutic agent or chemical substance, and still represents the principal side-effect restricting the use of cisplatin.

Objective: The aim of this study was to perform a biochemical, functional and histopathological investigation of the potential protective effect of eugenol against cisplatin-induced ototoxicity.

Methods: The study was performed with 24 female Sprague Dawley rats. Distortion product otoacoustic emissions tests were performed on all animals, which were randomized into four equal groups. A single intraperitoneal dose of 15mg/kg cisplatin was administered to cisplatin group, while the eugenol group received 100mg/kg eugenol intraperitoneal for five consecutive days. 100mg/kg eugenol was administered to cisplatin+eugenol group for 5 days. On the third day, these rats were received a single dose of 15mg/kg cisplatin. The control group was given 8mL/kg/day intraperitoneal saline solution for five days. The distortion product otoacoustic emissions test was repeated 24h after the final drug administration. All animals were sacrificed, and the cochleas were subsequently used for biochemical and histopathological examinations.

Results: Cisplatin caused oxidative stress in the cochlea, impaired the cochlear structure and significantly reduced signal noise ratio levels. Administration of eugenol together with cisplatin reversed these effects and provided functional, biochemical and histopathological protection.

Conclusion: The study findings represent the first indication in the literature that eugenol may protect against ototoxicity by raising levels of antioxidant enzymes and lowering those of oxidant parameters.

Keywords: 8-Hidroxi-2′-deoxiguanosina; 8-Hydroxy-2′-deoxyguanosine; Cisplatin-induced ototoxicity; DPOAE; EOAPD; Estresse oxidativo; Eugenol; Ototoxicidade induzida pela cisplatina; Oxidative stress.

MeSH terms

  • Animals
  • Antineoplastic Agents / toxicity*
  • Antioxidants / therapeutic use*
  • Cisplatin / toxicity*
  • Cochlea / drug effects
  • Cochlea / pathology
  • Disease Models, Animal
  • Eugenol / therapeutic use*
  • Female
  • Hearing Loss / chemically induced
  • Hearing Loss / prevention & control*
  • Otoacoustic Emissions, Spontaneous / drug effects
  • Rats
  • Rats, Sprague-Dawley


  • Antineoplastic Agents
  • Antioxidants
  • Eugenol
  • Cisplatin