Role of intravascular hemolysis on Priapism in transgenic sickle cell mice: therapeutic potential of haptoglobin

• Grant number: 19/17030-6
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2019
• End date: November 30, 2021
• Field of knowledge: Biological Sciences - Pharmacology - Autonomic Pharmacology
• Principal Investigator: Fábio Henrique da Silva
• Grantee: Pamela da Silva Pereira
• Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 17/08122-9 - Priapism and voiding dysfunction in Sickle Cell Disease: pathophysiology and new drug candidates, AP.JP

Abstract

In sickle cell anemia, intravascular hemolysis results in the release of hemoglobin to plasma. Under physiological conditions, haptoglobin is the plasma protein responsible for the body's defense against free hemoglobin accumulation. In plasma, haptoglobin binds to free hemoglobin and this complex is metabolized by macrophages in the reticuloendothelial system. However, in sickle cell anemia, high hemoglobin concentrations are released into plasma, saturating haptoglobin, and thus accumulating free hemoglobin in plasma. In plasma or interstitial space, hemoglobin reacts to nitric oxide (NO), generating nitrat and metahemoglobin. Reduced penile NO bioavailability has been identified as one of the main causes for triggering priapism in men with sickle cell anemia and mice transgenic sickle cell. Clinical studies have showed a strong positive correlation between priapism and high levels of intravascular hemolysis in men with sickle cell anemia. However, no study has evaluated the effect of intravascular hemolysis on erectile function in transgenic mice for sickle cell anemia. In the present study, we hypothesized that the reduction of NO bioavailability by hemoglobin in the penis contributes to priapism in sickle cell anemia. Thus, we propose to study the role of intravascular hemolysis in priapism in transgenic sickle cell mice and in C57BL/6 mice with phenylidrazine-induced intravascular hemolysis. It also aims to evaluate the effect of haptoglobin treatment on priapism in sickle cell anemia. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PEREIRA, PAMELA DA SILVA; PEREIRA, DALILA ANDRADE; CALMASINI, FABIANO BERALDI; REIS, LEONARDO O.; BRINKMAN, NATHAN; BURNETT, ARTHUR L.; COSTA, FERNANDO FERREIRA; SILVA, FABIO HENRIQUE. Haptoglobin treatment contributes to regulating nitric oxide signal and reduces oxidative stress in the penis: A preventive treatment for priapism in sickle cell disease. FRONTIERS IN PHYSIOLOGY, v. 13, p. 12-pg., 2022-09-13. (17/08122-9, 19/17030-6, 19/18886-1)