Radiation-induced enteropathy: molecular basis of pentoxifylline-vitamin E anti-fibrotic effect involved TGF-β1 cascade inhibition.

Details

Serval ID
serval:BIB_34B87A4C3B48
Type
Article: article from journal or magazin.
Collection
Publications
Title
Radiation-induced enteropathy: molecular basis of pentoxifylline-vitamin E anti-fibrotic effect involved TGF-β1 cascade inhibition.
Journal
Radiotherapy and oncology
Author(s)
Hamama S., Gilbert-Sirieix M., Vozenin M.C., Delanian S.
ISSN
1879-0887 (Electronic)
ISSN-L
0167-8140
Publication state
Published
Issued date
12/2012
Peer-reviewed
Oui
Volume
105
Number
3
Pages
305-312
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Radiation-induced fibrosis is a serious late complication of radiotherapy. Pentoxifylline-vitamin E has proven effective and safe in clinical trials in the treatment of fibrosis, while the molecular mechanism of its activity is yet unexplored.
Ten patients suffering from radiation-induced enteropathy were treated with pentoxifylline-vitamin E combination with SOMA score as the primary endpoint. In parallel, primary smooth muscle cells isolated from intestinal samples isolated from humans with radiation enteropathy were incubated with pentoxifylline, trolox (vit. E hydrophilic analogous) or their combination. Activation of the TGF-β1/Smad and Rho/ROCK pathways was subsequently investigated using Q-RT-PCR, gene reporter, Western-blot, ELISA and immunohistochemistry.
Pentoxifylline-vitamin E combination induces regression of symptoms (SOMA) by -41% and -80% at 6 and 18months. In vitro, pentoxifylline and trolox synergize to inhibit TGF-β1 protein and mRNA expression. This inhibitory action is mediated at the transcriptional level and leads to subsequent inhibition of TGF-β1/Smad targets (Col Iα1, FN1, PAI-1, CTGF), while it has no effect on the Rho/ROCK pathway.
The anti-fibrotic effect of combined pentoxifylline-vitamin E is at least in part mediated by inhibition of the TGF-β1 cascade. It strengthens previous clinical data showing pentoxifylline-vitamin E synergy and supports its use as a first-line treatment of radiation-induced fibrosis.

Keywords
Adult, Aged, Algorithms, Antioxidants/pharmacology, Antioxidants/therapeutic use, Blotting, Western, Clinical Trials as Topic, Enzyme-Linked Immunosorbent Assay, Female, Fibrosis/drug therapy, Fibrosis/etiology, Fibrosis/prevention & control, Humans, Immunohistochemistry, Intestinal Diseases/drug therapy, Intestinal Diseases/etiology, Intestinal Diseases/prevention & control, Male, Middle Aged, Pentoxifylline/pharmacology, Pentoxifylline/therapeutic use, Radiation-Protective Agents/pharmacology, Radiation-Protective Agents/therapeutic use, Radiotherapy/adverse effects, Reverse Transcriptase Polymerase Chain Reaction, Transforming Growth Factor beta1/drug effects, Treatment Outcome, Vitamin E/pharmacology, Vitamin E/therapeutic use
Pubmed
Web of science
Create date
17/04/2018 9:13
Last modification date
20/08/2019 13:21
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