Protective effect of α-lipoic acid against radiation-induced fibrosis in mice

// Seung-Hee Ryu 1 , Eun-Young Park 1 , Sungmin Kwak 3, 4 , Seung-Ho Heo 2 , Je-Won Ryu 2 , Jin-hong Park 1 , Kyung-Chul Choi 3, 4, * , Sang-wook Lee 1, * 1 Department of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea 2 Institute for Life Sciences, Asan Medical Center, Seoul, Korea 3 Department of Biomedical Sciences and Department of Pharmacology, Cell Dysfunction Research Center (CDRC), University of Ulsan College of Medicine, Seoul, Korea 4 Cell Dysfunction Research Center and Bio-Medical Institute of Technology (BMIT), University of Ulsan College of Medicine, Seoul, Korea * These authors contributed equally to this work Correspondence to: Sang-wook Lee, e-mail: lsw@amc.seoul.kr Kyung-Chul Choi, e-mail: choikc75@amc.seoul.kr Keywords: radiation-induced fibrosis, α-lipoic acid, acetylation, NF-κB, PAI-1 Received: July 07, 2015 Accepted: December 05, 2015 Published: January 20, 2016 ABSTRACT Radiation-induced fibrosis (RIF) is one of the most common late complications of radiation therapy. We found that α-lipoic acid (α-LA) effectively prevents RIF. In RIF a mouse model, leg contracture assay was used to test the in vivo efficacy of α-LA. α-LA suppressed the expression of pro-fibrotic genes after irradiation, both in vivo and in vitro , and inhibited the up-regulation of TGF-β1-mediated p300/CBP activity. Thus, α-LA prevents radiation-induced fibrosis (RIF) by inhibiting the transcriptional activity of NF-κB through inhibition of histone acetyltransferase activity. α-LA is a new therapeutic methods that can be used in the prevention-treatment of RIF.