Apohemoglobin-haptoglobin complex alleviates iron toxicity in mice with β-thalassemia via scavenging of cell-free hemoglobin and heme.

Abstract

β-thalassemia is a genetic hemoglobin (Hb) disorder that affects millions of people world-wide. It is characterized by ineffective erythropoiesis and anemia. The resultant chronic anemia can require life-long blood transfusion regimens, leading to secondary hemochromatosis. Moreover, the abnormal red blood cells (RBCs) from β-thalassemia patients are prone to hemolytic events that release cell-free Hb and heme causing a series of events that result in oxidative organ and tissue damage. In this study, β-thalassemic mice were treated with a protein scavenger for six weeks, apohemoglobin-haptoglobin (apoHb-Hp), this protein scavenges cell free Hb and heme. We hypothesize that scavenging cell-free Hb and heme will lead to a positive therapeutic event. After the apoHb-hp treatment it was observed to reduce the weight of the liver and spleen and show an improvement in liver function by a drop in ALT, AST, and ALP markers. ApoHb-hp treatment also hints at an improved RBC half-life as the number of reticulocytes decreased, the mean corpuscular volume (MCV) increased, mean corpuscular hemoglobin increase and the RBC distribution width decreased. Furthermore, apoHb-Hp treatment reduced circulating serum iron concentration and transferrin saturation concentration. Based on these outcomes, introducing a scavenger protein can benefit β-thalassemic mice. This study demonstrated that apoHb-Hp treatment may be a viable strategy to mitigate toxicities associated with cell free Hb and heme, a driver of β-thalassemic issues.

• Authors: Carlos J Munoz, Ivan S Pires, Vinay Jani, Srila Gopal, Andre F Palmer, Pedro Cabrales
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 156 Pg. 113911 (Dec 2022) ISSN: 1950-6007 [Electronic] France
• PMID: 36308920 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• Haptoglobins
• apohemoglobin
• Heme
• Hemoglobins
• Iron

Topics

• Mice
• Animals
• Haptoglobins (metabolism)
• Heme (metabolism)
• beta-Thalassemia (drug therapy)
• Hemoglobins (metabolism)
• Iron