Deferiprone can protect mitochondrial injury

This paper below is not about neuronal  but endothelial injury. It could well demonstrate similar type of problem we are seeing in neural tissues in overload of iron and perhaps also how deferiprone or PBT434 deals with this overload.  The paper wants to explain the thromboembolic complications of  thalassemia in which we have iron overload but in fact similar complications we can have also in other diseases when gradually developing iron overload.  I just wonder the difference between deferiprone and PBT434, is it BBB or is it side-effects or is that physiological iron balance is not disrupted as it may be the case with deferiprone.


Toxicol Appl Pharmacol. 2017 Nov 10. pii: S0041-008X(17)30442-8. doi: 10.1016/j.taap.2017.11.005. [Epub ahead of print]
Deferiprone inhibits iron overload-induced tissue factor bearing endothelial microparticle generation by inhibition oxidative stress induced mitochondrial injury, and apoptosis.

Chan S¹, Lian Q², Chen MP¹, Jiang D³, Ho JTK¹, Cheung YF¹, Chan GCF⁴.
Author information

1
Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, China.
2
Department of Medicine, LKS Faculty of Medicine, The University of Hong Kong, China; School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, China.
3
Department of Ophthalmology, LKS Faculty of Medicine, The University of Hong Kong, China.
4
Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, China. Electronic address: [email protected].
Abstract

Iron overload-induced cardiovascular toxicity is one of the most common causes of morbidity and mortality in beta-thalassemia major patients. We have previously shown that iron overload-induced systemic arterial changes characterized by endothelial dysfunction are associated with increased endothelial microparticle (EMP) release. In this study, we further demonstrate how EMP release is associated with iron-induced mitochondrial injury and apoptosis of endothelial cells. Iron increased the production of reactive oxygen species (ROS) and calcium influx into mitochondria [Ca²⁺]_m. Iron also disturbed mitochondrial respiration function and eventually led to loss of mitochondrial membrane potential (ΔΨ_m). A significant increase in apoptotic cells and EMPs were found under iron treatment. EMPs contained tissue factor (TF), which has potential clinical impact on thromboembolic phenomenon. Then, we investigated the salvaging effect of deferiprone (L1) on endothelial cell damage and EMP release. We found that L1 could inhibit iron-induced ROS generation, and decrease mitochondrial damage with the resultant effect of less endothelial cell apoptosis and EMP release. L1 could protect endothelial cells from iron-induced toxic effects and minimize EMP release, which could be potentially helpful in a subgroup of thalassemia patients who have increased thromboembolic complications.