Protective effect of esculentoside A on radiation-induced dermatitis and fibrosis.
OBJECTIVE
To investigate the effect of esculentoside A (EsA) on radiation-induced cutaneous and fibrovascular toxicity and its possible molecular mechanisms, both in vivo and in vitro.


METHODS
Mice received drug intervention 18 hours before 30 Gy to the right hind leg. Alterations in several cytokines expressed in skin tissue 2 days after irradiation were determined by ELISA. Early skin toxicity was evaluated 3 to 4 weeks after irradiation by skin scoring, and both tissue contraction and expression of TGF-beta1 were determined for soft-tissue fibrosis 3 months after irradiation. In vitro, the effect of EsA on radiation-induced nitric oxide (NO) and cytokine production in different cell types was measured by application of 2, 4, and 8 Gy.


RESULTS
In vivo, EsA reduced levels of IL-1alpha, MCP-1, VEGF, and TGF-beta1 in cutaneous tissue and reduced soft-tissue toxicity. In vitro, EsA inhibited the IL-1alpha ordinarily produced after 4 Gy in A431 cells. In Raw264.7 cells, EsA reduced levels of IL-1alpha, IL-1beta, and NO production costimulated by radiation and lipopolysaccharide (LPS). In L-929 cells, EsA inhibited VEGF, TNF, and MCP-1 production at 2, 4, and 8 Gy.


CONCLUSIONS
Esculentoside A protects soft tissues against radiation toxicity through inhibiting the production of several proinflammatory cytokines and inflammatory mediators in epithelial cells, macrophages, fibroblasts, and skin tissue.
Xiao
Zhenyu
Z
Department of Radiation Oncology, James P. Wilmot Cancer Center at the University of Rochester Medical Center, Rochester, NY, USA.
Su
Ying
Y
Yang
Shanmin
S
Yin
Liangjie
L
Wang
Wei
W
Yi
Yanghua
Y
Fenton
Bruce M
BM
Zhang
Lurong
L
Okunieff
Paul
P
D000818:Animals; D045744:Cell Line, Tumor / Q000378:metabolism / Q000528:radiation effects; D016207:Cytokines / Q000032:analysis; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects; D005355:Fibrosis / Q000517:prevention & control; D008264:Macrophages / Q000378:metabolism / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000032:analysis; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011855:Radiodermatitis / Q000378:metabolism / Q000517:prevention & control*; D012503:Saponins / Q000627:therapeutic use*; D012867:Skin / Q000473:pathology / Q000528:radiation effects*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1
D016207:Cytokines; D004365:Drugs, Chinese Herbal; D012503:Saponins; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D009569:Nitric Oxide; C076297:esculentoside A; D009828:Oleanolic Acid