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Effect of methylglyoxal and glucose on the function of human leukocytes: possible protective role of astaxantin and vitamin C

Grant number: 09/14382-7
Support type:Regular Research Grants
Duration: January 01, 2010 - March 31, 2012
Field of knowledge:Biological Sciences - Physiology - General Physiology
Principal Investigator:Rosemari Otton
Grantee:Rosemari Otton
Home Institution: Pró-Reitoria de Pós-Graduação e Pesquisa. Universidade Cruzeiro do Sul (UNICSUL). São Paulo , SP, Brazil

Abstract

The increasing incidence of diabetes mellitus (DM) is one of the major threats to human health nowadays. Hormonal changes, excessive caloric intake, physical inactivity and obesity have a significant influence on its pathogenesis, and the cell dysfunction and the insulin resistance are the principal events that cause the increase in plasma glucose (hyperglycemia). The presence of hyperglycemia favors the reaction of glucose molecules with amino groups of proteins, forming glycation-end products (AGEs). The pathological effects of AGEs are related to the ability of these compounds to modify the chemical properties and functions of various biological structures. The formation of AGEs is directly associated with the onset of diabetic complications. This study aims to evaluate the effect of concomitant treatment of methylglyoxal and glucose to induce AGEs and oxidative stress in leukocytes from human peripheral blood and the possible protective role of astaxanthin and vitamin C on the functional parameters of these cells. The evaluations to be performed include: cell viability by flow cytometry after treatment of cells with methylglyoxal (5 µM) and glucose (20 mM) in addition to treatment with ASTA (2 µM) and vitamin C (100 µM), DNA fragmentation, externalization of phosphatidylserine, activation of caspases and mitochondrial depolarization as parameters of cell death, production of pro- and anti-inflammatory interleukins, evaluation of lipid peroxidation (TBARS), oxidative damage to proteins (carbonyl and thiol), production of ROS/RNS by evaluation the production of superoxide anion, nitric oxide (NO) and hydrogen peroxide (H2O2), GSH/GSSG rate, intracellular calcium release, expression of adhesion molecules and receptors for AGEs. This study may contribute to the understanding of the involvement of AGEs in the function of immune cells and the possible intervention of ASTA and vitamin C in this process. (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)
BOLIN, A. P.; GUERRA, B. A.; NASCIMENTO, S. J. S.; OTTON, R. Changes in lymphocyte oxidant/antioxidant parameters after carbonyl and antioxidant exposure. International Immunopharmacology, v. 14, n. 4, p. 690-697, DEC 2012. Web of Science Citations: 6.
GUERRA, B. A.; BOLIN, A. P.; OTTON, R. Carbonyl stress and a combination of astaxanthin/vitamin C induce biochemical changes in human neutrophils. TOXICOLOGY IN VITRO, v. 26, n. 7, p. 1181-1190, OCT 2012. Web of Science Citations: 5.
GUERRA, BEATRIZ ALVES; BOLIN, ANAYSA PAOLA; MORANDI, ANA CAROLINA; OTTON, ROSEMARI. Glycolaldehyde impairs neutrophil biochemical parameters by an oxidative and calcium-dependent mechanism-Protective role of antioxidants astaxanthin and vitamin C. Diabetes Research and Clinical Practice, v. 98, n. 1, p. 108-118, OCT 2012. Web of Science Citations: 9.

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