title: Renal fibrogenesis and platinum compounds in a rat model: a novel Pt (II) complex vs. cisplatin.
abstract: OBJECTIVE
  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. The aim of the present study was to compare the nephrotoxic effects - particularly renal fibrogenesis- of PtAcacDMS and cisplatin in rats after the subcutaneous administration of a single dose (5 mg/Kg b.w., s.c.) of either compound to ten-day-old rats.
  
  
  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.
  
  
  CONCLUSIONS
  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 was proven suitable to investigate the occurrence of epithelial-mesenchymal transition (EMT) in renal fibrogenesis induced by the platinum-based compounds.
authors: Department of Biology and Biotechnology, University of Pavia, Pavia, Italy fenoglio@unipv.it.
authors: Carla
authors: C
authors: Fenoglio
authors: Department of Biology and Biotechnology, University of Pavia, Pavia, Italy.
authors: Federica
authors: F
authors: Albicini
authors: Department of Biotechnology and Environmental Science, University of Salento, Lecce, Italy.
authors: Sandra Angelica
authors: SA
authors: De Pascali
authors: Department of Biology and Biotechnology, University of Pavia, Pavia, Italy.
authors: Gloria
authors: G
authors: Milanesi
authors: Department of Biology and Biotechnology, University of Pavia, Pavia, Italy.
authors: Marco
authors: M
authors: Fumagalli
authors: Department of Biotechnology and Environmental Science, University of Salento, Lecce, Italy.
authors: Danilo
authors: D
authors: Migoni
authors: Department of Biotechnology and Environmental Science, University of Salento, Lecce, Italy.
authors: Francesco Paolo
authors: FP
authors: Fanizzi
authors: Department of Biology and Biotechnology, University of Pavia, Pavia, Italy.
authors: Graziella
authors: G
authors: Bernocchi
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis / Q000139:chemically induced*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008823:Micelles; D017671:Platinum Compounds / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D008823:Micelles; D017671:Platinum Compounds; D002945:Cisplatin
keywords: (Pt(O,O’-acac)(γ-acac)(DMS)); Cisplatin; epithelial-mesenchymal transition; renal fibrogenesis