Estudo da toxicidade induzida por metilglioxal em células sanguíneas humanas: efeito protetor do Syzigium cumini

Abstract

Methylglyoxal (MG) is a α-oxoaldehyde compound formed mainly as co-product from glycolysis. Due its high glicative capacity, it is considered the major precursor of advanced glycation end-products (AGEs). Although the compound is metabolized by different ways, high levels of MG are found in subjects with diabetes melittus, Alzheimer’s disease and cancer. Several works show that the toxicology of MG is related with glycative and oxidative stress. However, data about the precise toxic effects and mechanisms are still scarce in literature. The present study aimed analyze the cytotoxic effects induced by MG in the human blood cells, as well as to verify the possible preventive effect of an ethnopharmacological agent used in the treatment of different pathologies, especially diabetes mellitus: the aqueous leaves extract of Syzygium cumini (Ext). Erythrocytes, leukocytes and platelets were exposed to different concentrations of MG and time exposure. In Erythrocytes, the exposure to MG culminated with hemolysis, increase in osmotic fragility and decrease of the levels of free amino (NH3 +) groups. In leucocytes, the compound induced DNA damage, increase in the levels of fluorescent glycated products and decrease in the cell viability (especially of agranulocytes). A significant decrease in the activity of ectonucleotidases, nucleotidases and adenosine deaminase enzymes was verified in the platelets exposed to MG. The Ext treatment prevented most of detrimental effects elicited by MG toward blood cells, especially the hemolytic and genotoxic effects. In another set of experiments performed with leucocytes, the exposure to MG increased the levels of oxygen reactive species, the size and granularity of cells and induced apotosis/necrosis. These events were accompanied by changes in the mRNA expression of genes responsive to apoptosis (AIF, BAD, BCl-2), redox status (enzymes superoxide dismutase, catalase, glutathione-S-transferase and transcript factor Nrf2). An increase in the expression of AGEs receptor (RAGE) and glyoxalase 1 enzyme was also verified in these cells. The set of results obtained in this study will contribute to understand more accurately the effects that MG can cause on blood cells as well as indicate the plant S. cumini as a promising pharmacological agent against the toxic effects of MG.