Successful mitigation of delayed intestinal radiation injury using pravastatin is not associated with acute injury improvement or tumor protection.

Details

Serval ID
serval:BIB_9D918D402FE9
Type
Article: article from journal or magazin.
Collection
Publications
Title
Successful mitigation of delayed intestinal radiation injury using pravastatin is not associated with acute injury improvement or tumor protection.
Journal
International Journal of Radiation Oncology, Biology, Physics
Author(s)
Haydont V., Gilliot O., Rivera S., Bourgier C., François A., Aigueperse J., Bourhis J., Vozenin-Brotons M.C.
ISSN
0360-3016 (Print)
ISSN-L
0360-3016
Publication state
Published
Issued date
2007
Peer-reviewed
Oui
Volume
68
Number
5
Pages
1471-1482
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Abstract
PURPOSE: To investigate whether pravastatin mitigates delayed radiation-induced enteropathy in rats, by focusing on the effects of pravastatin on acute cell death and fibrosis according to connective tissue growth factor (CTGF) expression and collagen inhibition.
METHODS AND MATERIALS: Mitigation of delayed radiation-induced enteropathy was investigated in rats using pravastatin administered in drinking water (30 mg/kg/day) 3 days before and 14 days after irradiation. The ileum was irradiated locally after surgical exteriorization (X-rays, 19 Gy). Acute apoptosis, acute and late histologic alterations, and late CTGF and collagen deposition were monitored by semiquantitative immunohistochemistry and colorimetric staining (6 h, 3 days, 14 days, 15 weeks, and 26 weeks after irradiation). Pravastatin antitumor action was studied in HT-29, HeLa, and PC-3 cells by clonogenic cell survival assays and tumor growth delay experiments.
RESULTS: Pravastatin improved delayed radiation enteropathy in rats, whereas its benefit in acute and subacute injury remained limited (6 h, 3 days, and 14 days after irradiation). Delayed structural improvement was associated with decreased CTGF and collagen deposition but seemed unrelated to acute damage. Indeed, the early apoptotic index increased, and severe subacute structural damage occurred. Pravastatin elicited a differential effect, protecting normal intestine but not tumors from radiation injury.
CONCLUSION: Pravastatin provides effective protection against delayed radiation enteropathy without interfering with the primary antitumor action of radiotherapy, suggesting that clinical transfer is feasible.
Keywords
Animals, Apoptosis, Cell Line, Tumor, Collagen/metabolism, Collagen/radiation effects, Connective Tissue Growth Factor, Drug Evaluation, Preclinical, Female, Fibrosis, HT29 Cells, HeLa Cells, Humans, Ileum/pathology, Ileum/radiation effects, Immediate-Early Proteins/metabolism, Intercellular Signaling Peptides and Proteins/metabolism, Male, Mice, Mice, Nude, Pravastatin/therapeutic use, Radiation Injuries, Experimental/pathology, Radiation Injuries, Experimental/prevention & control, Radiation-Protective Agents/therapeutic use, Rats, Rats, Wistar
Pubmed
Create date
01/12/2014 17:28
Last modification date
20/08/2019 15:03
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