Hydrogen sulfide: A novel nephroprotectant against cisplatin-induced renal toxicity

George J. Dugbartey*, Hjalmar R. Bouma, Ian Lobb, Alp Sener

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

25 Citations (Scopus)

Abstract

Cisplatin is a potent chemotherapeutic agent for the treatment of various solid-organ cancers. However, a plethora of evidence indicates that nephrotoxicity is a major side effect of cisplatin therapy. While the antineoplastic action of cisplatin is due to formation of cisplatin-DNA cross-links, which damage rapidly dividing cancer cells upon binding to DNA, its nephrotoxic effect results from metabolic conversion of cisplatin into a nephrotoxin and production of reactive oxygen species, causing oxidative stress leading to renal tissue injury and potentially, kidney failure. Despite therapeutic targets in several pre-clinical and clinical studies, there is still incomplete protection against cisplatin-induced nephrotoxicity. Hydrogen sulfide (H2S), the third discovered gasotransmitter next to nitric oxide and carbon monoxide, has recently been identified in several in vitro and in vivo studies to possess specific antioxidant, anti-inflammatory and anti-apoptotic properties that modulate several pathogenic pathways involved in cisplatin-induced nephrotoxicity. The current article reviews the molecular mechanisms underlying cisplatin-induced nephrotoxicity and displays recent findings in the H2S field that could disrupt such mechanisms to ameliorate cisplatin-induced renal injury. (C) 2016 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)15-20
Number of pages6
JournalNitric oxide-Biology and chemistry
Volume57
DOIs
Publication statusPublished - 1-Jul-2016

Keywords

  • Cisplatin
  • Cisplatin-induced nephrotoxicity
  • Molecular mechanism
  • Reactive oxygen species (ROS)
  • Hydrogen sulfide (H2S)
  • H2S donor
  • INDUCED NEPHROTOXICITY
  • 3-MERCAPTOPYRUVATE SULFURTRANSFERASE
  • DIALLYL DISULFIDE
  • OXIDATIVE STRESS
  • TUBULAR CELLS
  • RATS
  • INJURY
  • INHIBITION
  • APOPTOSIS
  • DAMAGE

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