scholarly journals Quercetin Completely Ameliorates Hypoxia–Reoxygenation-Induced Pathophysiology Severity in NY1DD Transgenic Sickle Mice: Intrinsic Mild Steady State Pathophysiology of the Disease in NY1DD Is Also Reversed

Biomolecules ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1473
Author(s):  
Sangeetha Thangaswamy ◽  
Craig A. Branch ◽  
Kamalakar Ambadipudi ◽  
Seetharama A. Acharya

The vaso-occlusive crisis (VOC) is a major complication of sickle cell disease (SCD); thus, strategies to ameliorate vaso-occlusive episodes are greatly needed. We evaluated the therapeutic benefits of quercetin in a SCD transgenic sickle mouse model. This disease model exhibited very mild disease pathophysiology in the steady state. The severity of the disease in the NY1DD mouse was amplified by subjecting mice to 18 h of hypoxia followed by 3 h of reoxygenation. Quercetin (200 mg/kg body weight) administered to hypoxia challenged NY1DD mice in a single intraperitoneal (i.p.) dose at the onset of reoxygenation completely ameliorated all hypoxia reoxygenation (H/R)-induced pathophysiology. Additionally, it ameliorated the mild intrinsic steady state pathophysiology. These results are comparable with those seen with semisynthetic supra plasma expanders. In control mice, C57BL/6J, hypoxia reoxygenation-induced vaso-occlusion was at significantly lower levels than in NY1DD mice, reflecting the role of sickle hemoglobin (HbS) in inducing vaso-occlusion; however, the therapeutic benefits from quercetin were significantly muted. We suggest that these findings represent a unique genotype of the NY1DD mice, i.e., the presence of high oxygen affinity red blood cells (RBCs) with chimeric HbS, composed of mouse α-chain and human βS-chain, as well as human α-chain and mouse β-chain (besides HbS). The anti-anemia therapeutic benefits from high oxygen affinity RBCs in these mice exert disease severity modifications that synergize with the therapeutic benefits of quercetin. Combining the therapeutic benefits of high oxygen affinity RBCs generated in situ by chemical or genetic manipulation with the therapeutic benefits of antiadhesive therapies is a novel approach to treat sickle cell patients with severe pathophysiology.

Hemoglobin ◽  
1989 ◽  
Vol 13 (7-8) ◽  
pp. 637-647 ◽  
Author(s):  
Y. Ohba ◽  
K. Imai ◽  
R. Uenaka ◽  
M. Ami ◽  
K. Fujisawa ◽  
...  

Blood ◽  
1997 ◽  
Vol 89 (11) ◽  
pp. 4204-4212 ◽  
Author(s):  
R.A. Popp ◽  
D.M. Popp ◽  
S.G. Shinpock ◽  
M.Y. Yang ◽  
J.G. Mural ◽  
...  

Abstract Hemoglobin (Hb) S Antilles is a naturally occurring form of sickling human Hb but causes a more severe phenotype than Hb S. Two homozygous viable Hb S Antilles transgene insertions from Tg58Ru and Tg98Ru mice were bred into MHOAH mice that express high oxygen affinity (P50 ∼24.5 mm Hg) rather than normal (P50 ∼40 mm Hg) mouse Hbs. The rationale was that the high oxygen affinity MHOAH Hb, the lower oxygen affinity of Hb S Antilles than Hb S (P50 ∼40 v 26.5 mm Hg), and the lower solubility of deoxygenated Hb S Antilles than Hb S (∼11 v 18 g/dL) would favor deoxygenation and polymerization of human Hb S Antilles in MHOAH mouse red blood cells (RBCs). The Tg58 × Tg98 mice produced have a high and balanced expression (∼50% each) of hα and hβS Antilles globins, 25% to 35% of their RBCs are misshapen in vivo, and in vitro deoxygenation of their blood induces 30% to 50% of the RBCs to form classical looking, elongated sickle cells with pointed ends. Tg58 × Tg98 mice exhibit reticulocytosis, an elevated white blood cell count and lung and kidney pathology commonly found in sickle cell patients, which should make these mice useful for experimental studies on possible therapeutic intervention of sickle cell disease.


1975 ◽  
Vol 400 (2) ◽  
pp. 343-347 ◽  
Author(s):  
H.B. Kleckner ◽  
J.B. Wilson ◽  
J.G. Lindeman ◽  
P.D. Stevens ◽  
G. Niazi ◽  
...  

1995 ◽  
Vol 96 (6) ◽  
pp. 711-716 ◽  
Author(s):  
H. Wajcman ◽  
E. Girodon ◽  
D. Prom� ◽  
M.L. North ◽  
F. Plassa ◽  
...  

Author(s):  
Epifania Rita Testa ◽  
Adriana Masotti ◽  
Patrizia Valeri ◽  
Luciana Geremia ◽  
Valeria Brunetta ◽  
...  

Author(s):  
Abhay A Bhave ◽  
Lakshmi Iyer ◽  
Nawal Kazi ◽  
Manju Gorivale ◽  
Anita Nadkarni

High oxygen affinity haemoglobin variants are rare and often underdiagnosed in persistent erythrocytosis with no apparent aetiology. Here the author present a 29-year-old Indian male patient with a long-standing history of erythrocytosis which was incidentally detected. The proband had a prothrombotic family history of cerebral vessel stroke in his paternal grandfather at a young age and unexplained erythrocytosis in his father and brother. A review of his haemograms showed persistent high haemoglobin values. Routine tests did not reveal any specific aetiology and haemoglobin electrophoresis by High-Performance Liquid Chromatography (HPLC) showed absence of any abnormal peak or unstable haemoglobin. DNA sequencing of the β globin gene revealed heterozygosity for codon 20 {GTG→ATG, Valine (Val)→ Methionine (Met)} mutation confirming the presence of an electrophoretically silent Hb variant - Haemoglobin Olympia in him and his extended family members. This case study emphasises importance of this rare entity of high oxygen affinity haemoglobin variant as a differential diagnosis while screening for erythrocytosis. This is the first case report of Haemoglobin Olympia from India reported in the literature.


2016 ◽  
Vol 55 (3) ◽  
pp. 285-287
Author(s):  
Raku Son ◽  
Takakazu Higuchi ◽  
Atsushi Mizuno ◽  
Ryosuke Koyamada ◽  
Sadamu Okada ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document