Table 2.

Potential ROS-reducing agents studied in preclinical models

References	Agent	Mechanism	Stage	Result
Ref. 37	Monomethyl fumorate	Ntf2 induction and HbF induction	SCD mice	Reduces sickle retinopathy
Ref. 38	2-Cyano-3,12 dioxooleana-1,9 diene-28-imidazolide (Nrf2 inducer)	Nrf2 induction	SCD mice	Reduces inflammation and organ damages
Ref. 40	INK128 and sirolimus	Mammalian target of rapamycin inhibition	SCD mice	Reduces organ damages
Ref. 39	Sildenafil	Promotes endothelial NO synthase and inhibits NADPH oxidation	SCD mice	Protects vascular endothelium
Ref. 11	RN-1 (LSD-1 inhibitor)	Mitophagy induction and reduces SCD-RBC ROS	SCD mice	Increases SCD RBCs lifespan
Ref. 11	Sirolimus (mammalian target of rapamycin inhibitor)	Mitophagy induction and reduces SCD-RBC ROS	SCD mice	Increases SCD RBCs lifespan