The Cardioprotective Mechanism of Phenylaminoethyl Selenides (PAESe) Against Doxorubicin-Induced Cardiotoxicity Involves Frataxin

Fu Xiaoyu, Eggert Mathew, Yoo Sieun, Patel Nikhil, Zhong Juming, Steinke Ian, Govindarajulu Manoj, Turumtay Emine Akyuz, Mouli Shravanthi, Panizzi Peter, Beyers Ronald, Denney Thomas, Arnold Robert, Amin Rajesh H.; Front. Pharmacol., 12 April 2021 doi:10.3389/fphar.2020.574656

Mechanistically, we demonstrated that DOX impedes the stability of the iron-sulfur cluster biogenesis protein Frataxin (FXN) (0.5 fold), resulting in enhanced mitochondrial free iron accumulation (2.5 fold) and reduced aconitase activity (0.4 fold). Our findings further indicate that PAESe prevented the reduction of FXN levels and the ensuing elevation of mitochondrial free iron levels.