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

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European Archives of Oto-Rhino-Laryngology Aims and scope Submit manuscript

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.

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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

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Authors and Affiliations

  1. Department of Otorhinolaryngology, Otology Research Group, University Hospital of Puerta de Hierro-Majadahonda, Manuel de Falla 1, Majadahonda, 28222, Madrid, Spain

    Celia Casares, Rafael Ramírez-Camacho, Almudena Trinidad, Amaya Roldán & José Ramón García-Berrocal

  2. Department of Biochemistry, University Hospital of Puerta de Hierro-Majadahonda, Majadahonda, 28222, Madrid, Spain

    Eduardo Jorge

Authors
  1. Celia Casares
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  2. Rafael Ramírez-Camacho
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  3. Almudena Trinidad
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  4. Amaya Roldán
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  5. Eduardo Jorge
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  6. José Ramón García-Berrocal
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Correspondence to Almudena Trinidad.

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Casares, C., Ramírez-Camacho, R., Trinidad, A. et al. Reactive oxygen species in apoptosis induced by cisplatin: review of physiopathological mechanisms in animal models. Eur Arch Otorhinolaryngol 269, 2455–2459 (2012). https://doi.org/10.1007/s00405-012-2029-0

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  • DOI: https://doi.org/10.1007/s00405-012-2029-0

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