Mitigation of Lung Injury after Accidental Exposure to Radiation

Abstract

There is a serious need to develop effective mitigators against accidental radiation exposures. In radiation accidents, many people may receive nonuniform whole-body or partial-body irradiation. The lung is one of the more radiosensitive organs, demonstrating pneumonitis and fibrosis that are believed to develop at least partially because of radiation-induced chronic inflammation. Here we addressed the crucial questions of how damage to the lung can be mitigated and whether the response is affected by irradiation to the rest of the body. We examined the widely used dietary supplement genistein given at two dietary levels (750 or 3750 mg/kg) to Fischer rats irradiated with 12 Gy to the lung or 8 Gy to the lung + 4 Gy to the whole body excluding the head and tail (whole torso). We found that genistein had promising mitigating effects on oxidative damage, pneumonitis and fibrosis even at late times (36 weeks) when drug treatment was initiated 1 week after irradiation and stopped at 28 weeks postirradiation. The higher dose of genistein showed no greater beneficial effect. Combined lung and whole-torso irradiation caused more lung-related severe morbidity resulting in euthanasia of the animals than lung irradiation alone.

Short-Term Treatment with a SOD/Catalase Mimetic, EUK-207, Mitigates Pneumonitis and Fibrosis after Single-Dose Total-Body or Whole-Thoracic Irradiation

“…Molteni et al described a rat fractionated TBI model in which there was no mortality (3). Mahmood et al reported that genistein had mitigating effects on radiation-induced lung injuries in rats irradiated with either 12 Gy to the lung, or with 8 Gy to the lung and 4 Gy to the whole torso (22), doses that spare the bone marrow and gastrointestinal syndromes. Single-dose TBI (11 Gy) with BMT in our rat model did not induce pulmonary fibrosis before rats were lost to radiation nephropathy starting around 120 days (data not shown).…”

“…Molteni et al (3) described fractionated TBI in a rat model and demonstrated reduction of lung injury by ACE inhibitors started 10 days before radiation. In addition, Mahmood et al (22) reported that genistein mitigated lung injuries caused by combined irradiation of 4 Gy TBI plus an additional 8 Gy to the whole thorax of rats.…”

Mitigation of Radiation-Induced Lung Injury with EUK-207 and Genistein: Effects in Adolescent Rats

“…We and others have previously reported on the use of genistein and other antioxidants as potential protectors or mitigators of radiation-induced lung damage (15–18). In the current study, we extended our previous work (18) studying genistein as a mitigator by altering the administration from a dietary supplement to daily subcutaneous injection to avoid issues with intestinal absorption and reduced food intake.…”

Pre-clinical research in small animals using radiotherapy technology – a bidirectional translational approach

“…Both the intracranial and the skinfold window enable target localisation by confocal or stereoscopic microscopy. Several publications report on irradiation of the whole lung or torso of mice and rats to investigate radiation-induced effects in lung tissue [159][160][161]. For whole lung irradiation, the animal is immobilised in an acrylic jig containing an anaesthetic gas distributor and two lead collimators with respective apertures.…”

“…Irradiation is delivered by single or opposing vertical fixed beams of the X-RAD 225Cx operated at 100 or 225 kV with proper collimation. Additional measurements are reported using radiochromic films in situ [156,158] or in a solid water phantom [159].…”