Studies on pentoxifylline and tocopherol combination for radiation-induced heart disease in rats.
OBJECTIVE
To investigate whether the application of pentoxifylline (PTX) and tocopherol l (Vit. E) could modify the development of radiation-induced heart disease and downregulate the expression of transforming growth factor (TGF)-beta1mRNA in rats.


METHODS
A total of 120 Sprague-Dawley rats were separated into four groups: control group, irradiated group, experimental group 1, and experiment group 2. Supplementation was started 3 days before irradiation; in experimental group 1, injection of PTX (15 mg/kg/d) and Vit. E (5.5 mg/kg/d) continued till the 12th week postirradiation, whereas in experimental group 2 it was continued until the 24th week postirradiation. All rats were administrated a single dose of 20 Gy irradiation to the heart except the control group. Histopathologic evaluation was performed at various time points (Days 1, 2, 4, 8, and 12 and 24th week) up to 24 weeks after irradiation. Changes of levels of TGF-beta1 mRNA expression were also investigated at the same time points using competitive polymerase chain reaction.


RESULTS
Compared with the irradiated group, levels of TGF-beta1 mRNA of the rat hearts were relatively low in the two experimental groups on the 12th week postirradiation. In experimental group 1, there was a rebound expression of TGF-beta1 mRNA on the 24th week postirradiation, whereas that of the experimental group 2 remained low (p < 0.05). The proportions of collagen fibers of the two experimental groups were lower than that of irradiated group (p < 0.05). A rebound could be observed in the experimental group 1.


CONCLUSIONS
PTX and Vit. E downregulated the expression of TGF-beta1 mRNA. The irradiated rat hearts showed a marked pathologic response to the drugs. The withdrawal of drugs in the 12th week postirradiation could cause rebound effects of the development of fibrosis.
Liu
Hui
H
State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, P.R. China.
Xiong
Mai
M
Xia
Yun-Fei
YF
Cui
Nian-Ji
NJ
Lu
Ru-Biao
RB
Deng
Ling
L
Lin
Yue-Hao
YH
Rong
Tie-Hua
TH
D000818:Animals; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004359:Drug Therapy, Combination; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D006321:Heart / Q000187:drug effects / Q000528:radiation effects*; D006331:Heart Diseases; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010431:Pentoxifylline / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D011832:Radiation Injuries / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D024505:Tocopherols / Q000627:therapeutic use*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D012333:RNA, Messenger; D011837:Radiation-Protective Agents; D053773:Transforming Growth Factor beta1; D024505:Tocopherols; D010431:Pentoxifylline