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European Journal of Clinical Pharmacology

, Volume 69, Issue 11, pp 1863–1874 | Cite as

Signalling mechanisms involved in renal pathological changes during cisplatin-induced nephropathy

  • Siddesh Jaiman
  • Arun Kumar Sharma
  • Kulwant Singh
  • Deepa KhannaEmail author
Review Article

Abstract

Context

Cisplatin, a coordination platinum complex, is used as a potential anti-neoplastic agent, having well recognized DNA-damaging property that triggers cell-cycle arrest and cell death in cancer therapy. Beneficial chemotherapeutic actions of cisplatin can be detrimental for kidneys.

Background

Unbound cisplatin gets accumulated in renal tubular cells, leading to cell injury and death. This liable action of cisplatin on kidneys is mediated by altered intracellular signalling pathways such as mitogen-activated protein kinase (MAPK), extracellular regulated kinase (ERK), or C- Jun N terminal kinase/stress-activated protein kinase (JNK/SAPK). Further, these signalling alterations are responsible for release and activation of tumour necrosis factor (TNF-α), mitochondrial dysfunction, and apoptosis, which ultimately cause the renal pathogenic process. Cisplatin itself enhances the generation of reactive oxygen species (ROS) and activation of nuclear factor-κB (NF-κB), inflammation, and mitochondrial dysfunction, which further leads to renal apoptosis. Cisplatin-induced nephropathy is also mediated through the p53 and protein kinase-Cδ (PKCδ) signalling pathways.

Objective

This review explores these signalling alterations and their possible role in the pathogenesis of cisplatin-induced renal injury.

Keywords

Cisplatin MAPKs family p53 PKCδ ROS Renal injury 

Abbreviations

MAPKs

Mitogen activated protein kinases

ERK

Extracellular regulated kinase

JNK

Jun N terminal kinase

SAPKs

Stress-activated protein kinases

PKCδ

Protein kinase-Cδ

ROS

Reactive oxygen species

ATF3

Activating transcription factor 3

GPCRs

G protein coupled receptors

RTKs

Receptor tyrosine kinases

iNOS

Inducible nitric oxide synthase

TNF-α

Tumour necrosis factor

NF-κB

Nuclear factor- κB

PIDD

p53-inducible death domain

PUMA

p53-upregulated modulator of apoptosis

H2O2

Hydrogen peroxide

Notes

Acknowledgments

We express our gratefulness to Dr. Pitchai Balakumar forhis expertise, suggestions and review; gratitude is extended to Dr. Rajendar Singh, Chairman, and Shri Om Parkash, Director, Mr. Sanjeev Kalra, Administrator, Rajendra Institute of Technology and Sciences, Sirsa, India, for their inspiration and constant support.

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Siddesh Jaiman
    • 1
  • Arun Kumar Sharma
    • 1
  • Kulwant Singh
    • 1
  • Deepa Khanna
    • 1
    • 2
    Email author
  1. 1.Cardiovascular Pharmacology Division, Department of PharmacologyRajendra Institute of Technology and SciencesSirsaIndia
  2. 2.Department of Pharmacology, Cardiovascular Pharmacology DivisionInstitute of Pharmacy, Rajendra Institute of Technology and Sciences (RITS)SirsaIndia

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