[Radiation-induced cutaneo-muscular fibrosis (III): major therapeutic efficacy of liposomal Cu/Zn superoxide dismutase].
Sub-cutaneous and muscular fibrosis are common and irreversible late effect of radiation on normal tissues. An experiment was designed to test the effectiveness of superoxide dismutase in reducing late radiation injury. This study was performed in an experimental porcine model of acute localized gamma irradiation simulating human accidental overexposure: 12 Large White pigs were irradiated on the thigh with a collimated gamma 192Ir source, so that the dose was 160 Gy/skin (100%) and 40 Gy/2 cm depth (25%). In this model, fibrosis appears in 4 to 5 months. The heterogeneous sclerotic tissue is composed of stable fibrotic areas poorly cellularized and active areas with a high density of myofibroblasts and inflammatory perifibrotic part. Lipsod administration modalities were six intramuscular injections during 3 weeks (twice weekly) either 10 mg/inj (five pigs) or of 100 mg/inj (five pigs). A methodic evaluation by two examiners consisted of measurements being taken before and after treatment: sum of the two largest perpendicular measurable dimensions, cutaneous projected surface of palpated fibrotic block, ultrasound fibrosis deepness and extrapolated volume. We conclude that Lipsod is the first drug ever described that reduces radiation-induced fibrosis. Its efficacy in this model was highly significant, with a regression higher than 40% in size and 70% in surface and volume, 12 weeks after the end of treatment. This response was rapid, reproducible without dose-effect or toxicity in the limits studied. This work confirms previously published results in humans.
Lefaix
J L
JL
Département de pathologie et toxicologie expérimentales, CEN Saclay, Gif-sur-Yvette, France.
Delanian
S
S
Leplat
J J
JJ
Tricaud
Y
Y
Martin
M
M
Hoffschir
D
D
Daburon
F
F
Baillet
F
F
D000818:Animals; D004337:Drug Carriers; D005355:Fibrosis / Q000209:etiology / Q000473:pathology / Q000628:therapy; D007273:Injections, Intramuscular; D008081:Liposomes; D009132:Muscles / Q000528:radiation effects; D009135:Muscular Diseases / Q000473:pathology / Q000628:therapy; D011833:Radiation Injuries, Experimental / Q000150:complications*; D011855:Radiodermatitis / Q000473:pathology / Q000628:therapy; D015203:Reproducibility of Results; D012867:Skin / Q000528:radiation effects; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000627:therapeutic use*; D013552:Swine
D004337:Drug Carriers; D008081:Liposomes; D013482:Superoxide Dismutase
La fibrose cutanéo-musculaire radio-induite (III): efficacité thérapeutique majeure de la superoxyde dismutase Cu/Zn liposomiale.