Striking regression of subcutaneous fibrosis induced by high doses of gamma rays using a combination of pentoxifylline and alpha-tocopherol: An experimental study
Jl. Lefaix et al., Striking regression of subcutaneous fibrosis induced by high doses of gamma rays using a combination of pentoxifylline and alpha-tocopherol: An experimental study, INT J RAD O, 43(4), 1999, pp. 839-847
Citations number
57
Categorie Soggetti
Radiology ,Nuclear Medicine & Imaging","Onconogenesis & Cancer Research
Journal title
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
Purpose: To establish a successful treatment of subcutaneous fibrosis devel
oping after high doses of gamma rays, suitable for use in clinical practice
.
Methods and Materials: We used an animal model of acute localized gamma irr
adiation simulating accidental overexposure in humans. Three groups of 5 La
rge White pigs were irradiated using a collimated Ir-192 source to deliver
a single dose of 160 Gy onto the skin surface (100%) of the outer side of t
he thigh. A well-defined block of necrosis developed within a few weeks whi
ch had healed after 26 weeks to leave a block of subcutaneous fibrosis invo
lving skin and skeletal muscle. One experimental group of 5 pigs was dosed
orally for 26 weeks starting 26 weeks after irradiation with 1600 mg/120 kg
body weight of pentoxifylline (PTX) included in the reconstituted food dur
ing its fabrication, and another group of 5 was dosed orally for the same p
eriod with a daily dose of 1600 mg/120 kg body weight of PTX combined with
2000 IU/120 kg body weight of alpha-tocopherol. Five irradiated control pig
s were given normal food only. Animals were assessed for changes in the den
sity of the palpated fibrotic block and in the dimensions of the projected
cutaneous surface. Depth of scar tissue was determined by ultrasound. Physi
cal and sonographic findings were confirmed by autopsy 26 weeks after treat
ment started. The density, length, width, and depth of the block of fibroti
c scar tissue, and the areas and volume of its projected cutaneous surface,
were compared before treatment, 6 and 13 weeks thereafter, and at 26 weeks
.
Results: The experimental animals exhibited no change in behavior and no ab
normal clinical or anatomic signs. No modifications were observed in the bl
ock of fibrotic scar tissue of pigs dosed with PTX alone. However, signific
ant softening and shrinking of this block were noted in the pigs dosed with
PTX + alpha-tocopherol 13 weeks after treatment started and at autopsy, wh
en mean regression was similar to 30% for length, similar to 50% for width
and depth, and similar to 70% for area and volume. Histologic examination s
howed completely normal muscle and subcutaneous tissue surrounding the resi
dual scar tissue. The 50% decrease in the linear dimensions of the scar tis
sue, were comparable to the results obtained in our previous clinical studi
es, and were highly significant compared to the clinical and autopsy result
s for the controls. Histologic examination of the residual scar tissue reve
aled tissue which was more homogenous and less cellular and inflammatory th
an in control and PTX-dosed pigs. The tissular and cellular immunolocalizat
ion of tumor necrosis factor alpha (TNF alpha) was similar in the residual
fibrotic tissues of all three groups of pigs, whereas the immunostaining of
transforming growth factor beta-1(TGF beta-1) diminished much more in the
residual fibrotic scar tissue of the PTX + alpha-tocopherol-dosed pigs than
in the two other groups.
Conclusions: The present results showed a striking regression of the subcut
aneous fibrotic scar tissue that develops as a consequence of high doses of
gamma rays. (C) 1999 Elsevier Science Inc.