W1237 Haptoglobin Poymorphisms are Associated With Ulcerative Colitis and Crohn's Disease

Marquez, Lucía; Cleynen, Isabelle; Machiels, Kathleen; Organe, Sophie; Ferrante, Marc; Henckaerts, Liesbet; Ballet, Vera; Rutgeerts, Paul; Vermeire, Séverine

doi:10.1016/s0016-5085(10)63129-0

Cited by 2 publications

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The β-chain encompasses 245 amino acids and is not polymorphic. As shown in Figure 5, Hp 1-1 is the smallest haptoglobin protein structure [106,107,108). Further research proved that the ability of Hp to lay off damage prompted by free radicals is largely phenotype pendent.…”

Section: Haptoglobin (Hp)mentioning

confidence: 96%

Inflammatory Bowel Disease-Associated Colorectal Cancer: Translational and Transformational Risks from Exogenous Free Hemoglobin Alpha Chain: A By-product of Extravasated Erythrocyte Macrophage Erythrophagocytosis

Bragg,

Breaux,

M'Koma

2023

Preprint

View full text Add to dashboard Cite

The aggregate aftermath of persistent inflammation in patients with inflammatory bowel disease (IBD) places them at increased risk for the advancement to colitis-associated colorectal cancer (CACRC). CACRC is preceded by IBD, the highly heterogenous, pharmacologically incurable, pertinacious, reverting/worsening, and immune-mediated inflammatory pathologies of the colon and rectum. The molecular and immunological basis of CACRC is highly correlated with the length/duration and stringency/severity of colon inflammation predisposed by the exogenous/free hemoglobin alpha chain (HbαC) the byproduct of infiltrating immune cells, extravasated erythrocytes, and macrophage erythrophagocytosis. The exogenous free HbαC prompts oxygen-free radical-arbitrated DNA damage (DNAD) through increased cellular reactive oxygen species (ROS) exacerbated by decreased tissue antioxidant defenses. Mitigation of Fenton reaction via pharmaceutical therapy would attenuate the ROS, promote apoptosis, DNAD repair, and subsequent prevent the incidence of CACRC. Three pharmaceutical options that attenuate hemoglobin toxicity include haptoglobin, deferoxamine, and flavonoids (vitamins C/E). Haptoglobin’s clearance rare from plasma is inversely correlated with its size; the smaller the size, the faster the clearance. Thus, the administration of Hp1-1 may prove to be beneficial. Furthermore, deferoxamine’s hydrophilic structure limits its ability to cross cell membranes. Thus, it may be beneficial if administered intracellularly to avoid the higher plasma concentrations and longer incubation periods associated with extracellular administration. Finally, the effectiveness of flavonoids and natural herb antioxidants is associated with high reactivity of hydroxyl substituents. Multiple analyses are currently underway to assess the clinical context of CACRC and outline the molecular basis of HbαC-induced ROS pathogenesis by exposing colonocytes and/or colonoids to HbαC. These cells are then treated with haptoglobin, deferoxamine (DFO), and flavonoids in order to separate free HbαC and measure their impact on hydroxyl radical formation therapies. The molecular pathogenesis of sporadic colorectal cancer (SCRC) i.e., “inflammation-dysplasia-carcinoma” progression sequence is well described, but the immunopathogenesis of CACRC herein reviewed is broadly still in prodromal stage/phase to be validated and understood. Therefore this timely review outlines the molecular and immunological basis of disease pathogenesis and the pharmaceutical intervention as a protective measure for CACRC.

show abstract

Section: Haptoglobin (Hp)mentioning

confidence: 96%

Inflammatory Bowel Disease-Associated Colorectal Cancer: Translational and Transformational Risks from Exogenous Free Hemoglobin Alpha Chain: A By-product of Extravasated Erythrocyte Macrophage Erythrophagocytosis

Bragg,

Breaux,

M'Koma

2023

Preprint

View full text Add to dashboard Cite

show abstract

“…The β-chain encompasses 245 amino acids and is not polymorphic. As shown in Figure 5 , Hp1-1 is the smallest haptoglobin protein structure [ 107 , 108 , 109 ]. Further research has proven that the ability of Hp to avoid damage inflicted by free radicals is largely phenotype-pendent.…”

Section: Pharmaceutical Approach To Preventing Colitis-associated Col...mentioning

confidence: 99%

Inflammatory Bowel Disease-Associated Colorectal Cancer: Translational and Transformational Risks Posed by Exogenous Free Hemoglobin Alpha Chain, a By-Product of Extravasated Erythrocyte Macrophage Erythrophagocytosis

Bragg,

Breaux,

M’Koma

2023

Medicina

View full text Add to dashboard Cite

Colonic inflammatory bowel disease (IBD) encompasses ulcerative colitis (UC) and Crohn’s colitis (CC). Patients with IBD are at increased risk for colitis-associated colorectal cancer (CACRC) compared to the general population. CACRC is preceded by IBD, characterized by highly heterogenous, pharmacologically incurable, pertinacious, worsening, and immune-mediated inflammatory pathologies of the colon and rectum. The molecular and immunological basis of CACRC is highly correlated with the duration and severity of inflammation, which is influenced by the exogenous free hemoglobin alpha chain (HbαC), a byproduct of infiltrating immune cells; extravasated erythrocytes; and macrophage erythrophagocytosis. The exogenous free HbαC prompts oxygen free radical-arbitrated DNA damage (DNAD) through increased cellular reactive oxygen species (ROS), which is exacerbated by decreased tissue antioxidant defenses. Mitigation of the Fenton Reaction via pharmaceutical therapy would attenuate ROS, promote apoptosis and DNAD repair, and subsequently prevent the incidence of CACRC. Three pharmaceutical options that attenuate hemoglobin toxicity include haptoglobin, deferoxamine, and flavonoids (vitamins C/E). Haptoglobin’s clearance rate from plasma is inversely correlated with its size; the smaller the size, the faster the clearance. Thus, the administration of Hp1-1 may prove to be beneficial. Further, deferoxamine’s hydrophilic structure limits its ability to cross cell membranes. Finally, the effectiveness of flavonoids, natural herb antioxidants, is associated with the high reactivity of hydroxyl substituents. Multiple analyses are currently underway to assess the clinical context of CACRC and outline the molecular basis of HbαC-induced ROS pathogenesis by exposing colonocytes and/or colonoids to HbαC. The molecular immunopathogenesis pathways of CACRC herein reviewed are broadly still not well understood. Therefore, this timely review outlines the molecular and immunological basis of disease pathogenesis and pharmaceutical intervention as a protective measure for CACRC.

show abstract

W1237 Haptoglobin Poymorphisms are Associated With Ulcerative Colitis and Crohn's Disease

Cited by 2 publications

References 0 publications

Inflammatory Bowel Disease-Associated Colorectal Cancer: Translational and Transformational Risks from Exogenous Free Hemoglobin Alpha Chain: A By-product of Extravasated Erythrocyte Macrophage Erythrophagocytosis

Inflammatory Bowel Disease-Associated Colorectal Cancer: Translational and Transformational Risks from Exogenous Free Hemoglobin Alpha Chain: A By-product of Extravasated Erythrocyte Macrophage Erythrophagocytosis

Inflammatory Bowel Disease-Associated Colorectal Cancer: Translational and Transformational Risks Posed by Exogenous Free Hemoglobin Alpha Chain, a By-Product of Extravasated Erythrocyte Macrophage Erythrophagocytosis

Contact Info

Product

Resources

About