Abstract
Background/Aim: 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. 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 was proven suitable to investigate the occurrence of epithelial-mesenchymal transition (EMT) in renal fibrogenesis induced by the platinum-based compounds.
| Original language | English |
|---|---|
| Pages (from-to) | 739-751 |
| Number of pages | 13 |
| Journal | Anticancer Research |
| Volume | 35 |
| Issue number | 2 |
| Publication status | Published - Feb 1 2015 |
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Keywords
- (Pt(O,O′-acac)(γ-acac)(DMS))
- Cisplatin
- Epithelial-mesenchymal transition
- Renal fibrogenesis
ASJC Scopus subject areas
- Cancer Research
- Oncology
- Medicine(all)
Cite this
Renal fibrogenesis and platinum compounds in a rat model : A novel Pt (II) complex vs. cisplatin. / Fenoglio, Carla; Albicini, Federica; De Pascali, Sandra Angelica; Milanesi, Gloria; Fumagalli, Marco; Migoni, Danilo; Fanizzi, Francesco Paolo; Bernocchi, Graziella.
In: Anticancer Research, Vol. 35, No. 2, 01.02.2015, p. 739-751.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Renal fibrogenesis and platinum compounds in a rat model
T2 - A novel Pt (II) complex vs. cisplatin
AU - Fenoglio, Carla
AU - Albicini, Federica
AU - De Pascali, Sandra Angelica
AU - Milanesi, Gloria
AU - Fumagalli, Marco
AU - Migoni, Danilo
AU - Fanizzi, Francesco Paolo
AU - Bernocchi, Graziella
PY - 2015/2/1
Y1 - 2015/2/1
N2 - Background/Aim: 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. 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 was proven suitable to investigate the occurrence of epithelial-mesenchymal transition (EMT) in renal fibrogenesis induced by the platinum-based compounds.
AB - Background/Aim: 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. 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 was proven suitable to investigate the occurrence of epithelial-mesenchymal transition (EMT) in renal fibrogenesis induced by the platinum-based compounds.
KW - (Pt(O,O′-acac)(γ-acac)(DMS))
KW - Cisplatin
KW - Epithelial-mesenchymal transition
KW - Renal fibrogenesis
UR - http://www.scopus.com/inward/record.url?scp=84923649395&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84923649395&partnerID=8YFLogxK
M3 - Article
C2 - 25667453
AN - SCOPUS:84923649395
VL - 35
SP - 739
EP - 751
JO - Anticancer Research
JF - Anticancer Research
SN - 0250-7005
IS - 2
ER -