Protective effects of amifostine, curcumin, and melatonin against cisplatin-induced acute kidney injury
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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.
KeywordsAmifostine Cisplatin Curcumin Melatonin Nephrotoxicity
TM and FM conceived and designed the research. TM conducted the experiments. AY contributed new reagents or analytical tools. TM, FM, AY, AT, and LT analyzed the data. TM, FM, and AT wrote the manuscript. All authors read and approved the manuscript.
This work was supported by the Scientific Research Projects Unit of Recep Tayyip Erdogan University [TSA-2016-652, 2016].
Compliance with ethical standards
The study was approved by the Institutional Ethics committee and observed the ethical principles of the Declaration of Helsinki.
Conflict of interest
The authors declare that they have no conflicts of interest.
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