Hydrogen sulfide: A novel nephroprotectant against cisplatin-induced renal toxicity.
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.
Department of Medicine, Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA; Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands. Electronic address: george_dugbartey@urmc.rochester.edu.
George J
GJ
Dugbartey
Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Hjalmar R
HR
Bouma
Matthew Mailing Center for Translational Transplant Studies, London Health Sciences Center, Western University, London, ON, Canada; Department of Microbiology and Immunology, London Health Sciences Center, Western University, London, ON, Canada.
Ian
I
Lobb
Matthew Mailing Center for Translational Transplant Studies, London Health Sciences Center, Western University, London, ON, Canada; Department of Microbiology and Immunology, London Health Sciences Center, Western University, London, ON, Canada; Department of Surgery, Division of Urology, London Health Sciences Center, Western University, London, ON, Canada; Department of Surgery, Division of Urology, University of Manitoba, Winnepeg, MB, Canada; Multi-Organ Transplant Program, Western University, London Health Sciences Center, Western University, London, ON, Canada.
Alp
A
Sener
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis; D002945:Cisplatin / Q000009:adverse effects*; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism / Q000494:pharmacology*; D007674:Kidney Diseases / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D020011:Protective Agents / Q000378:metabolism / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D000975:Antioxidants; D020011:Protective Agents; D002945:Cisplatin; D006862:Hydrogen Sulfide
Cisplatin; Cisplatin-induced nephrotoxicity; H(2)S donor; Hydrogen sulfide (H(2)S); Molecular mechanism; Reactive oxygen species (ROS)