Protective effects of amifostine, curcumin, and melatonin against cisplatin-induced acute kidney injury

Naunyn Schmiedebergs Arch Pharmacol. 2018 Sep;391(9):915-931. doi: 10.1007/s00210-018-1514-4. Epub 2018 Jun 2.

Abstract

Despite the enormous advances made in the field of oncology, no solution to the side effect of nephrotoxicity caused by cisplatin used as an antineoplastic agent for approximately 40 years has yet been discovered. This study investigated the effects of cisplatin on the kidney, the damage mechanism involved, and the potential capacity of agents such as amifostine, curcumin, and melatonin to elicit a future therapeutic protocol in cisplatin-induced nephrotoxicity at the ultrastructural and molecular levels. Our study consisted of five groups: control (saline solution only; group 1), cisplatin (cisplatin only; group 2), cisplatin + amifostine (group 3), cisplatin + curcumin (group 4), and cisplatin + melatonin (group 5). Rats in all groups except the control group were administered a single intraperitoneal dose of 7.5 mg/kg cisplatin. All animals were sacrificed under anesthesia on the sixth day after cisplatin administration. Cisplatin increased serum urea and serum creatinine levels and caused an increase in tubular necrosis scores (TNS), HPS, NF-κB/p65, 8-OHdG, and caspase-3 expressions (p < 0.05). Additionally, we observed basal membrane thickening in glomerules, intense electron deposition in the subendothelial region, and atypical folds in podocyte pedicels. Amifostine, curcumin, and melatonin reduced the increases in serum urea and serum creatinine levels following cisplatin administration and reduced the levels of TNS, HPS, NF-κB/p65, 8-OHdG, and caspase-3 expressions (p < 0.05). ROS-scavenging antioxidants may be a promising means of preventing acute kidney disease in patients using cisplatin in the treatment of malignant tumors.

Keywords: Amifostine; Cisplatin; Curcumin; Melatonin; Nephrotoxicity.

MeSH terms

  • Acute Kidney Injury / chemically induced
  • Acute Kidney Injury / drug therapy*
  • Acute Kidney Injury / pathology
  • Amifostine / therapeutic use*
  • Animals
  • Antineoplastic Agents
  • Antioxidants / therapeutic use*
  • Cisplatin
  • Curcumin / therapeutic use*
  • Male
  • Melatonin / therapeutic use*
  • Rats, Sprague-Dawley

Substances

  • Antineoplastic Agents
  • Antioxidants
  • Curcumin
  • Melatonin
  • Amifostine
  • Cisplatin