European Archives of Oto-Rhino-Laryngology

, Volume 269, Issue 12, pp 2455–2459

Reactive oxygen species in apoptosis induced by cisplatin: review of physiopathological mechanisms in animal models

  • Celia Casares
  • Rafael Ramírez-Camacho
  • Almudena Trinidad
  • Amaya Roldán
  • Eduardo Jorge
  • José Ramón García-Berrocal
Review Article

DOI: 10.1007/s00405-012-2029-0

Cite this article as:
Casares, C., Ramírez-Camacho, R., Trinidad, A. et al. Eur Arch Otorhinolaryngol (2012) 269: 2455. doi:10.1007/s00405-012-2029-0

Abstract

Cisplatin is a highly effective chemotherapeutic agent but displays significant ototoxic side effects. The most prominent change seen in the cochlea after cisplatin administration consists of loss of outer hair cells. Several mechanisms are believed to mediate cisplatin-induced apoptosis: binding of cisplatin to guanine bases on DNA and the formation of inter- and intra-strand chain cross-linking, generation of reactive oxygen species (ROS) with increased lipid peroxidation and Ca2+ influx and, finally, inflammation mediated by cisplatin. The aim of the present review is to analyze the role of ROS in the mechanisms causing cisplatin-mediated apoptosis in the inner ear and the contribution of the different pathways involved, emphasizing the main strategies to blockade events leading to apoptosis of cochlear cells.

Keywords

Cisplatin Cochlea ROS Apoptosis Caspases Inflammation 

Abbreviations

STAT1

Signal transducer and activator of transcription-1

TRPV1

Transient receptor vanilloid-1

siRNA

Short interfering RNA

ROS

Reactive oxygen species

NOX3

NADPH nicotinamide adenine dinucleotide phosphate oxidase isoform, nitro-l-arginine methyl ester

IL-1β

Interleukin-1β

TNF-α

Tumor necrosis factor-α

HSP70

Heat shock protein 70

HSP32

Heat shock protein 32

HO-1

Heme oxygenase-1

iNOS

Inducible nitric oxide synthase

NF-kβ

Nuclear factor-kβ

COX-2

Cyclooxygenase-2

TRAIL

TNF-related apoptosis-inducing ligand

Cyt-c

Cytochrome c

AIF

Apoptosis-inducing factor

PARP

Poly (ADP-ribose) polymerase

JNK-c

Jun N-terminal kinase

RIP1

Kinase receptor interacting protein-1

TRAF2

TNF receptor-associated factor-2

SOD

Superoxide dismutase

GSH

Glutathione

AP1

Transcription activator protein-1

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Celia Casares
    • 1
  • Rafael Ramírez-Camacho
    • 1
  • Almudena Trinidad
    • 1
  • Amaya Roldán
    • 1
  • Eduardo Jorge
    • 2
  • José Ramón García-Berrocal
    • 1
  1. 1.Department of Otorhinolaryngology, Otology Research GroupUniversity Hospital of Puerta de Hierro-MajadahondaMadridSpain
  2. 2.Department of BiochemistryUniversity Hospital of Puerta de Hierro-MajadahondaMadridSpain

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