Erythrocyte redox metabolism: implications for melatonin usage in the treatment of people with sickle cell anemia

• Grant number: 15/25983-2
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: March 01, 2016
• End date: January 31, 2019
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Sayuri Miyamoto
• Grantee: Danilo Grunig Humberto da Silva
• Host Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil
• Associated research grant: 13/07937-8 - Redoxome - Redox Processes in Biomedicine, AP.CEPID

Abstract

As red blood cells (RBCs) emerge from the bone marrow, they lose all the ability of cell division, protein and lipid synthesis and oxidative phosphorylation. Despite this limited metabolic machinery, the RBCs are able to perform their functional role that mainly involves the transport and supply of oxygen (O2) to the tissues. Along the way, erythrocytes face i) osmotic shock; ii) the integrity of their membranes is constantly challenged; iii) they are exposed to pro-oxidant effects of reactive oxygen species (ROS) produced in the circulation; etc. Additionally, RBCs have an internal environment with constant ROS production, whose main source is O2-carrier protein, named hemoglobin (Hb). This protein undergoes auto-oxidation, producing methemoglobin and superoxide. In order to counteract oxidative stress, erythrocytes have a competent and self-sustaining antioxidant defense system. However, sickle erythrocytes containing an Hb with altered structure and physicochemical properties (HbS) have constant generation of pro-oxidants, compromising the ability of these cells to deal with oxidative stress, which results in a state of redox imbalance. Thus, the research of new, more sensitive and specific biomarkers related to erythrocyte redox metabolism is valid and potentially useful both for identifying high risk of oxidative damage, and to evaluate new antioxidant therapies. In this context, this study aims to evaluate possible direct and indirec modulator effects of melatonin treatment on red cell metabolism, using a suspension of sickle erythrocytes as experimental model.

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)

HUMBERTO DA SILVA, DANILO GRUNIG; CHAVES, NAYARA ALVES; MIYAMOTO, SAYURI; DE ALMEIDA, EDUARDO ALVES. Melatonin as an alternative and promising therapy for people with sickle cell anemia. Free Radical Biology and Medicine, v. 120, p. 1-pg., 2018-05-20. (13/07937-8, 15/25983-2)

CHAVES, NAYARA ALVES; PIRES ALEGRIA, THIAGO GERONIMO; DANTAS, LUCAS SOUZA; SOARES NETTO, LUIS EDUARDO; MIYAMOTO, SAYURI; BONINI DOMINGOS, CLAUDIA REGINA; HUMBERTO DA SILVA, DANILO GRUNIG. Impaired antioxidant capacity causes a disruption of metabolic homeostasis in sickle erythrocytes. Free Radical Biology and Medicine, v. 141, p. 34-46, SEP 2019. (13/07937-8, 15/25983-2)

HUMBERTO DA SILVA, DANILO GRUNIG; CHAVES, NAYARA ALVES; MIYAMOTO, SAYURI; DE ALMEIDA, EDUARDO ALVES. Prolonged erythrocyte auto-incubation as an alternative model for oxidant generation system. TOXICOLOGY IN VITRO, v. 56, p. 62-74, APR 2019. (13/07937-8, 15/25983-2)