title: Sustained treatment of sickle cell mice with haptoglobin increases HO-1 and H-ferritin expression and decreases iron deposition in the kidney without improvement in kidney function.
abstract: There is growing evidence that extracellular haemoglobin and haem mediate inflammatory and oxidative damage in sickle cell disease. Haptoglobin (Hp), the scavenger for free haemoglobin, is depleted in most patients with sickle cell disease due to chronic haemolysis. Although single infusions of Hp can ameliorate vaso-occlusion in mouse models of sickle cell disease, prior studies have not examined the therapeutic benefits of more chronic Hp dosing on sickle cell disease manifestations. In the present study, we explored the effect of Hp treatment over a 3-month period in sickle mice at two dosing regimens: the first at a moderate dose of 200 mg/kg thrice weekly and the second at a higher dose of 400 mg/kg thrice weekly. We found that only the higher dosing regimen resulted in increased haem-oxygenase-1 and heavy chain ferritin (H-ferritin) expression and decreased iron deposition in the kidney. Despite the decreased kidney iron deposition following Hp treatment, there was no significant improvement in kidney function. However, there was a nearly significant trend towards decreased liver infarction.
authors: Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA.
authors: Patricia A
authors: PA
authors: Shi
authors: Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA.
authors: Erika
authors: E
authors: Choi
authors: Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
authors: Narendranath R
authors: NR
authors: Chintagari
authors: Department of Hematology, Oncology, and Transplantation, University of Minnesota Medical School, Minneapolis, MN, USA.
authors: Julia
authors: J
authors: Nguyen
authors: Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA.
authors: Xinhua
authors: X
authors: Guo
authors: Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA.
authors: Karina
authors: K
authors: Yazdanbakhsh
authors: Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA.
authors: Narla
authors: N
authors: Mohandas
authors: Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
authors: Abdu I
authors: AI
authors: Alayash
authors: Department of Pathology, University of South Alabama School of Medicine, Birmingham, AL, USA.
authors: Elizabeth A
authors: EA
authors: Manci
authors: Department of Hematology, Oncology, and Transplantation, University of Minnesota Medical School, Minneapolis, MN, USA.
authors: John D
authors: JD
authors: Belcher
authors: Department of Hematology, Oncology, and Transplantation, University of Minnesota Medical School, Minneapolis, MN, USA.
authors: Gregory M
authors: GM
authors: Vercellotti
mesh_terms: D000755:Anemia, Sickle Cell / Q000150:complications / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001052:Apoferritins / Q000235:genetics / Q000378:metabolism*; D001772:Blood Cell Count; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D006242:Haptoglobins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D007674:Kidney Diseases / Q000209:etiology / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016896:Treatment Outcome
chemical_list: D006242:Haptoglobins; D001052:Apoferritins; D007501:Iron; D051547:Heme Oxygenase-1
keywords: H-ferritin; free haemoglobin; haem-oxygenase-1; haptoglobin; sickle cell disease