Developmental toxicity of auranofin in zebrafish embryos.
Auranofin (AF) is used in clinic for the treatment of rheumatoid arthritis, repurposing of AF as an anticancer drug has just finished a phase I/II clinical trial, but the developmental toxicity of AF remains obscure. This study focused on its developmental toxicity by using zebrafish embryos. Zebrafish embryos were exposed to different concentrations (1, 2.5, 5, 10 μm) of AF from 2 h post-fertilization (hpf) to 72 hpf. At 72 hpf, two major developmental defects caused by AF were found, namely severe pericardial edema and hypopigmentation, when embryos were exposed to concentrations higher than 2.5 μm. Biochemical detection of oxidative stress enzyme combined with expressions of a series of genes related to oxidative stress, cardiac, metal stress and pigment formation were subsequently tested. The superoxide dismutase activity was decreased while malondialdehyde content was accumulated by AF treatment. The expression of oxidative stress-related genes (sod1, gpx1a, gst), pigment-related genes (mitfb, trp-1a) and one metal stress-related gene ctr1 were all decreased by AF exposure. The expressions of cardiac-related genes (amhc, vmhc) and one metal-related gene hsp70 were found to be significantly upregulated by AF exposure. These findings indicated the potential developmental toxicity of AF on zebrafish early development. Copyright © 2016 John Wiley & Sons, Ltd.
College of Pharmacy, Yanbian University, Yanji, 133002, People's Republic of China.
Xiao-Yan
XY
Gao
Institute of Translational Medicine, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, 211800, People's Republic of China.
Kang
K
Li
Institute of Translational Medicine, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, 211800, People's Republic of China.
Ling-Ling
LL
Jiang
Institute of Translational Medicine, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, 211800, People's Republic of China.|State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, Nanjing, 211816, People's Republic of China.|Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing, 211816, People's Republic of China.
Ming-Fang
MF
He
College of Pharmacy, Yanbian University, Yanji, 133002, People's Republic of China.
Cun-Hai
CH
Pu
College of Pharmacy, Yanbian University, Yanji, 133002, People's Republic of China.
Dongzhou
D
Kang
College of Pharmacy, Yanbian University, Yanji, 133002, People's Republic of China.|Institute of Translational Medicine, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, 211800, People's Republic of China.|State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, Nanjing, 211816, People's Republic of China.|Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing, 211816, People's Republic of China.|Jiangsu Branch of China Academy of Science & Technology Development, Nanjing, People's Republic of China.
Jingjing
J
Xie
D000818:Animals; D018501:Antirheumatic Agents / Q000633:toxicity*; D001310:Auranofin / Q000633:toxicity*; D004487:Edema / Q000139:chemically induced / Q000473:pathology; D004625:Embryo, Nonmammalian; D047108:Embryonic Development / Q000187:drug effects*; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000187:drug effects; D017496:Hypopigmentation / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D008315:Malondialdehyde / Q000378:metabolism; D008670:Metals / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects; D013312:Stress, Physiological / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D013723:Teratogens; D015027:Zebrafish
D018501:Antirheumatic Agents; D008670:Metals; D013723:Teratogens; D001310:Auranofin; D008315:Malondialdehyde; D013482:Superoxide Dismutase
Auranofin; Cardiac toxicity; Developmental toxicity; Hypopigmentation; Zebrafish