Scholarship 22/10548-2 - Anemia falciforme, Óxido nítrico - BV FAPESP
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To investigate the contribution of intravascular hemolysis to functional and molecular changes in the bladder in a model of intravascular hemolysis induced by phenylhydrazine (PHZ)

Grant number: 22/10548-2
Support Opportunities:Scholarships in Brazil - Master
Start date until: September 01, 2022
End date until: February 29, 2024
Field of knowledge:Biological Sciences - Pharmacology - Autonomic Pharmacology
Principal Investigator:Fábio Henrique da Silva
Grantee:Tammyris Helena Rebecchi e Silveira
Host Institution: Universidade São Francisco (USF). Campus Bragança Paulista. Bragança Paulista , SP, Brazil
Associated research grant:17/08122-9 - Priapism and voiding dysfunction in Sickle Cell Disease: pathophysiology and new drug candidates, AP.JP

Abstract

Epidemiological studies indicate an association between sickle cell anemia and LUTS, but the pathophysiological mechanisms involved remain poorly understood. Only four experimental studies aim to understand voiding dysfunction in sickle cell anemia; therefore, the pathophysiology is still poorly explored. In sickle cell anemia, high heme concentrations are released from the hemoglobin in the plasma, saturating the hemopexin, thus accumulating free heme in the plasma. Heme can activate endothelial cells through the Toll-like receptor 4 (TLR4), leading to vascular inflammation and oxidative stress. Increased oxidative stress can reduce the bioavailability of nitric oxide (NO) since excess superoxide anion reacts with NO, as well as free hemoglobin can react with NO. In the present project, we hypothesized that reduced NO bioavailability by hemoglobin or oxidative stress in the lower genitourinary tract contributes to bladder overactivity in SCD. Indeed, excess reactive oxygen species in the lower urinary tract appear to contribute to voiding dysfunction in animals. In an animal model of overactive bladder, a previous study showed that male NO-deficient mice present detrusor hypertrophy and hyperactivity. In the present project, as mentioned above, we hypothesized that the reduced bioavailability of NO by hemoglobin in the lower genitourinary tract contributes to bladder overactivity in sickle cell anemia. Therefore, we propose to study the role of intravascular hemolysis in lower genitourinary tract function in C57BL/6 mice with phenylhydrazine-induced intravascular hemolysis. (AU)

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