Oral deferiprone administration ameliorates cisplatin-induced nephrotoxicity in rats

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 5^th 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.

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