Oral deferiprone administration ameliorates cisplatin-induced nephrotoxicity in rats

  • J Pharm Pharmacol. 2018 Oct;70(10):1357-1368. doi: 10.1111/jphp.12990.
Pouran Makhdoumi  1  2 ,  Khalil Abnous  3 ,  Soghra Mehri  4  3 ,  Leila Etemad  3 ,  Mohsen Imenshahidi  4  3 ,  Gholamreza Karimi  4  3
Affiliations
  • 1. Student Research Committee, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad, Iran.
  • 2. Pharmaceutical Research Center, Mashhad, Iran.
  • 3. Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
  • 4. Department of Pharmacodynamics and Toxicology, Pharmacy School, Mashhad University of Medical Sciences, Mashhad, Iran.
PMID: 30051477 DOI: 10.1111/jphp.12990
Abstract

Objectives: Cisplatin is one of the widely used antitumour agents with major clinical side effect, nephrotoxicity. We showed the role of iron in cisplatin-induced nephrotoxicity that entrance to the cell via Transferrin Receptor (TfR) as a gatekeeper for iron uptake. We also examined the effect of iron chelator deferiprone against this toxicity.

Methods: Thirty male Wistar rats were randomly divided into six groups. Group I (saline orally for 10 days); group II (saline orally for 10 days plus single injection of cisplatin 7 mg/kg, intraperitoneally on 5th day); groups III, IV and V (deferiprone 50, 100 and 200 mg/kg orally for 10 days, respectively, plus cisplatin on 5th day). Group VI (deferiprone, orally).

Results: Deferiprone provided functional and significant histological-proven protection in group IV. Deferiprone attenuated the increased creatinine, BUN, malondialdehyde and iron concentrations in cisplatin-injected Animals. The increased amounts of TfR and decreased levels of HIF-1α and related anti-apoptotic genes expression in cisplatin-treated Animals were improved by deferiprone.

Conclusions: The results supported a role for iron in cisplatin-induced nephrotoxicity and TfR may serve as an important source of iron. Based on these findings, deferiprone pretreatment may play a role in preventing cisplatin-induced nephropathy in Cancer patient.

Keywords
HIF-1α; Iron; cisplatin; deferiprone; nephrotoxicity; transferrin.
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