Renal Fibrogenesis and Platinum Compounds in a Rat Model: A Novel Pt (II) Complex vs. Cisplatin

Abstract. Background: A new platinum compound, (Pt(O,O’-acac)(γ-acac)(DMS)) (PtAcacDMS), has been shown to possess higher cytotoxic activity than cisplatin on several cancer and chemoresistant cell lines. Aim: To compare the nephrotoxic effects -particularly renal fibrogenesis- of PtAcacDMS and cisplatin in rats after the subcutaneous administration of a single dose (5mg/Kg b.w., s.c.) of either compound to ten-day-old rats. Materials and Methods: Control and treated rats were killed 1 day (PD11), 7 days (PD17), 21 days (PD31) and 40 days (PD50) after the injection. Kidneys were processed for light and electron microscopy, and platinum determination. Antibodies against E- cadherin (E-cad), vimentin (VIM) and α-smooth muscle actin (αSMA) were used to identify epithelial and mesenchymal cells. Results and Conclusion: Cisplatin produced progressive cortical fibrotic lesions displaying a variable number of VIM-positive tubules and interstitial αSMA-positive cells around. By contrast, PtAcacDMS induced a minimal number of histopathological changes, which declined in the adult samples, while the renal platinum content was generally higher after PtAcacDMS than after cisplatin. The present experimental model has proved suitable to investigate the occurrence of epithelialmesenchymal transition (EMT) in renal fibrogenesis induced by the platinum-based compounds.