Roxadustat Markedly Reduces Myocardial Ischemia Reperfusion Injury in Mice
Hiroko Deguchi, Masataka Ikeda, Tomomi Ide, Tomonori Tadokoro, Soichiro Ikeda, Kosuke Okabe, Akihito Ishikita, Keita Saku, Shouji Matsushima, Hiroyuki Tsutsui, Hiroko Deguchi, Masataka Ikeda, Tomomi Ide, Tomonori Tadokoro, Soichiro Ikeda, Kosuke Okabe, Akihito Ishikita, Keita Saku, Shouji Matsushima, Hiroyuki Tsutsui
Abstract
Background: Ischemic preconditioning (IPC) is an effective procedure to protect against ischemia/reperfusion (I/R) injury. Hypoxia-inducible factor-1α (Hif-1α) is a key molecule in IPC, and roxadustat (RXD), a first-in-class prolyl hydroxylase domain-containing protein inhibitor, has been recently developed to treat anemia in patients with chronic kidney disease. Thus, we investigated whether RXD pretreatment protects against I/R injury.Methods and Results:RXD pretreatment markedly reduced the infarct size and suppressed plasma creatinine kinase activity in a murine I/R model. Analysis of oxygen metabolism showed that RXD could produce ischemic tolerance by shifting metabolism from aerobic to anaerobic respiration.
Conclusions: RXD pretreatment may be a novel strategy against I/R injury.
Keywords: Hypoxia-inducible factor-1α (Hif-1α); Ischemia/reperfusion injury; Roxadustat.
Source: PubMed