A. Prestes, M. D. dos Santos, A. Ecker, D. Zanini, M. Schetinger, D. B. Rosemberg, J. D. da Rocha, N. V. Barbosa
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Evaluation of methylglyoxal toxicity in human erythrocytes, leukocytes and platelets
Abstract Methylglyoxal (MG) is a reactive dicarbonyl metabolite originated mainly from glucose degradation pathway that plays an important role in the pathogenesis of diabetes mellitus (DM). Reactions of MG with biological macromolecules (proteins, DNA and lipids) can induce cytotoxicity and apoptosis. Here, human erythrocytes, leukocytes and platelets were acutely exposed to MG at concentration ranging from 0.025 to 10 mM. Afterwards, hemolysis and osmotic fragility in erythrocytes, DNA damage and cell viability in leukocytes, and the activity of purinergic ecto-nucleotidases in platelets were evaluated. The levels of glycated products from leukocytes and free amino groups from erythrocytes and platelets were also measured. MG caused fragility of membrane, hemolysis and depletion of amino groups in erythrocytes. DNA damage, loss of cell viability and increased levels of glycated products were observed in leukocytes. In platelets, MG inhibited the activity of enzymes NTPDase, 5′-nucleotidase and adenosine deaminase (ADA) without affecting the levels of free amino groups. Our findings provide insights for understanding the mechanisms involved in MG acute toxicity towards distinct blood cells.
期刊介绍:
Toxicology Mechanisms and Methods is a peer-reviewed journal whose aim is twofold. Firstly, the journal contains original research on subjects dealing with the mechanisms by which foreign chemicals cause toxic tissue injury. Chemical substances of interest include industrial compounds, environmental pollutants, hazardous wastes, drugs, pesticides, and chemical warfare agents. The scope of the journal spans from molecular and cellular mechanisms of action to the consideration of mechanistic evidence in establishing regulatory policy.
Secondly, the journal addresses aspects of the development, validation, and application of new and existing laboratory methods, techniques, and equipment. A variety of research methods are discussed, including:
In vivo studies with standard and alternative species
In vitro studies and alternative methodologies
Molecular, biochemical, and cellular techniques
Pharmacokinetics and pharmacodynamics
Mathematical modeling and computer programs
Forensic analyses
Risk assessment
Data collection and analysis.