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

  • Review Article
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

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.

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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

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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.

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The authors declare that they have no conflict of interest.

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  1. Cardiovascular Pharmacology Division, Department of Pharmacology, Rajendra Institute of Technology and Sciences, Sirsa, 125 055, India

    Siddesh Jaiman, Arun Kumar Sharma, Kulwant Singh & Deepa Khanna

  2. Department of Pharmacology, Cardiovascular Pharmacology Division, Institute of Pharmacy, Rajendra Institute of Technology and Sciences (RITS), Sirsa, 125 055, India

    Deepa Khanna

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  1. Siddesh Jaiman
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Jaiman, S., Sharma, A.K., Singh, K. et al. Signalling mechanisms involved in renal pathological changes during cisplatin-induced nephropathy. Eur J Clin Pharmacol 69, 1863–1874 (2013). https://doi.org/10.1007/s00228-013-1568-7

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