Signalling mechanisms involved in renal pathological changes during cisplatin-induced nephropathy.
BACKGROUND
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.
Cardiovascular Pharmacology Division, Department of Pharmacology, Rajendra Institute of Technology and Sciences, Sirsa, 125 055, India.
Siddesh
S
Jaiman
Arun Kumar
AK
Sharma
Kulwant
K
Singh
Deepa
D
Khanna
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D051745:Protein Kinase C-delta / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D051745:Protein Kinase C-delta; D020928:Mitogen-Activated Protein Kinases; D005978:Glutathione; D002945:Cisplatin