Effect Of Icaritin On Mitigating Radiation Injury Of Soft Tissue

Background and objective With the development of radiotherapytechnology and extensive application of multidisciplinary treatmentmodalities, radiation therapy has become one of the three anti-tumortherapy methods. Because patient’s skin and soft tissue is a necessaryway of external irradiation, tumor patients with radiotherapy almostsuffer the radiation injury of soft tissue. Radiation induced soft tissueinjury, especially fibrosis, seriously affects the patient’s quality oflife, and even lead to death. There is no clinical effective and safedrug on prevention and treatment of radiation induced soft tissue injury.In recent years, people turn to study the radiation protection effectof cheap traditional Chinese herbal medicine with non-toxic or lowtoxicity. In this study, we hope to investigate the effect of icaritin(ICT)on radiation-induced soft tissue injury and its related mechanism.Materials and methods①Twenty-fourth C57BL/6mice with radiationinduced soft tissue injury were divided into3groups, control group(none irradiated), model group (right hind limb received single dose of30Gy irradiation) and ICT treatment group (irradiation plus ICT5mg/kg).Then the acute dermatitis and chronic soft tissue fibrosis ofright hind limb were compared among three groups. Radiation induceddermatitis of mice was evaluated by skin score according to the area ofhair removal and the degree of skin damage. Degree of soft tissue fibrosiswas evaluated with the degree of right hind limb contracture which wasdefined as the difference of length from hip joint and knee joint betweenthe irradiated right hind limb and normal left hind limb.②RAW264.7cells seeded at cell culture plate were divided into3groups, controlgroup (none irradiated), solvent control group (irradiation with4Gy)and ICT group (irradiation plus ICT10ug/ml). IL-1β、IL-6、TNF-αand TGF-βl concentration was measured by ELISA, Reactive Oxygen Species (ROS)production and Nicotinamide Adenine Dinucleotide Phosphate(NADPH)oxidase activity by flow cytometry, NADPH oxidase RNA expression levelby RT-PCR24h and48h after irradiation respectively. Results①ICTsignificantly reduced the radiation dermatitis scores of the irradiatedright hind limbs of mice at28th days after irradiation(U=-3.049,P=0.002), and significantly reduced the differences of two lengthsbetween the irradiated right hind limb and normal left hind limb of miceat90th days after irradiation(U=-3.251, P=0.001).②ICT reduced thesecretion level of IL-1β, IL-6, the TNF-α and TGF-βl (P=0.001,0.003,＜0.001and＜0.001,respectively), ROS production (P＜0.001),theactivity of NADPH oxidase (P=0.002) and the RNA expression level of NADPHoxidase (P=0.026) of RAW264.7cell48hours after received radiation.Conclusion ICT can mitigate the mice acute radiation dermatitis andlater radiation fibrosis of soft tissue. Its mechanism may be relatedwith that ICT inhibits the inflammatory cytokine secretion at theinflammatory stage of pro-fibrosis.