TY  - EJOU
AU  - Bayomi, Hala S. 
AU  - Elsherbiny, Nehal M. 
AU  - El-Gayar, Amal M. 
AU  - Al-Gayyar, Mohammed M. H. 

TI  - Evaluation of renal protective effects of inhibiting TGF-β type I receptor in a cisplatin-induced nephrotoxicity model
T2  - European Cytokine Network

PY  - 2013
VL  - 24
IS  - 4
SN  - 1952-4005

AB  - Purpose: The use of cisplatin, the first of the platinum-containing anti-cancer drugs, is limited by
the development of a myriad of adverse reactions, including nephrotoxicity. We conducted this study therefore
to find out whether SB-431542, potent and specific inhibitor of type I transforming growth factor-beta receptor
(TGF-βR1), could prevent or attenuate kidney damage in rats, and to elucidate its possible mechanism of action.
Methods: Fifty rats were treated with cisplatin (10 mg/kg) in the presence (1 and 3 mg/kg) or absence of SB-431542.
Morphological changes were assessed in kidney sections stained with H/E. Oxidative stress was evaluated in kidney
homogenates by measuring malondialdehyde (MDA) and superoxide dismutase (SOD). Kidney samples were used
for measurements of TGF-βR1, TGF-β1 and sCD93 by ELISA. Kidney tissue apoptosis was assessed by measuring
caspase-3 activity. Results: The renal protective effect of SB-431542 was confirmed by the normal appearance of
renal tissue and the relatively unaffected serum creatinine and urea levels. With SB-431542, there was significantly
lower renal MDA and increased SOD compared with the cisplatin group. Furthermore, in the SB-431542 group,
renal TGF-βR1, TGF-β1, sCD93 and caspase-3 levels were significantly lower. Conclusions: Inhibition of TGF-
βR1 provides protective effects against cisplatin-induced nephrotoxicity through several mechanisms, including
attenuation of oxidative stress, inhibition of pro-inflammatory cytokines, blocking of renal fibrosis markers, and
anti-apoptotic effects.
KW  - caspase-3
KW  -  cisplatin
KW  -  MDA
KW  -  SB-431542
KW  -  sCD93
KW  -  SOD
KW  -  TGF-β1
KW  -  TGF-βR1

DO  - 10.1684/ecn.2014.0344