Treating Radiation Induced Skin Injury and Fibrosis Using Small Molecule Thiol Modifying Agents
Technical Report,30 Sep 2015,29 Sep 2016
THOMAS JEFFERSON UNIV PHILADELPHIA PA PHILADELPHIA United States
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Two separate experiments where used to explore the effects of RTA 408 and metformin in mitigating the effects of radiation. In our first experiment we used a combined injurysimultaneous radiation model whereby a 2X2 cm wound was created on the abdomen of the rat with immediate radiation of 20Gy being delivered. They were then followed out 6 weeks and photos were taken weekly to determine if the study drugs where having an effect. No significant effects were found by administering RTA-408 or metformin. A trend towards faster wound healing was observed. The second experiment was designed to look at the delayed effects of radiation. Animals were subjected to 40 Gy of radiation in 4 fractions of 10 gy over the course of a week. During this radiation they received DMSO vehicle control or RTA408. The animals were allowed to go through acute healing from the radiation and at 6 weeks they were challenged with a surgical insult of a rotational flap designed on the abdomen. The heartiness of the flap was measured by degree of necrosis after the animals were sacrificed 1 week postop. Findings confirmed RTA-408 when delivered during radiation resulted in significant improvement in flap survival. This is consistent with the conclusion that the benefit of RTA408 is less relevant in the acute wound healing setting but affects mechanisms relevant to resolution of radiation damage and, potentially chronic inflammation.
- Medicine and Medical Research
- Radioactivity, Radioactive Wastes and Fission Products