title: Aminoguanidine treatment increased NOX2 response in diabetic rats: Improved phagocytosis and killing of Candida albicans by neutrophils.
abstract: In this study, we show that aminoguanidine (AMG), an inhibitor of protein glycation, increases the NOX2 (phagocyte NADPH oxidase) response and microbicidal activity by neutrophils, regardless of diabetic status. The non-enzymatic glycation of proteins, yielding irreversible advanced glycation end products (AGEs), is involved in the development of diabetes complications, including alterations of signaling pathways and the generation of reactive oxygen species by phagocytes. The phagocytes produce ROS (reactive oxygen species) through activation of the NOX2 complex, which generates superoxide. The purpose of this study was to evaluate the effect of hyperglycemia and the glycation of proteins on the NOX2 activity of neutrophils and its implications for cellular physiology, with a focus on the microbicidal activity of these cells. We treated diabetic rats with AMG and evaluated neutrophil ROS generation and Candida albicans killing ability. We observed a large increase in the microbicidal activity of peritoneal neutrophils from AMG-treated rats. The increase was independent of diabetic status and myeloperoxidase activity. Collectively, our results suggest that AMG has an immunomodulator role that triggers an increase in the microbicidal response of neutrophils mainly related to reactive oxygen species production by NOX2.
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, UNIFAL-MG, Alfenas, MG, Brazil.
authors.forename: Cláudia
authors.initials: C
authors.lastname: de Souza Ferreira
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, UNIFAL-MG, Alfenas, MG, Brazil.
authors.forename: Paula Commune
authors.initials: PC
authors.lastname: Pennacchi
authors.affiliation: Departamento de Histologia, Instituto de Ciências Biomédicas, UNIFAL MG, Alfenas, MG, Brazil.
authors.forename: Tomaz Henrique
authors.initials: TH
authors.lastname: Araújo
authors.affiliation: Setor de Virologia, Instituto Adolfo Lutz, São Paulo, SP, Brazil.
authors.forename: Noemi Nosomi
authors.initials: NN
authors.lastname: Taniwaki
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, UNIFAL-MG, Alfenas, MG, Brazil.
authors.forename: Fernanda Borges
authors.initials: FB
authors.lastname: de Araújo Paula
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, UNIFAL-MG, Alfenas, MG, Brazil.
authors.forename: Stella Maris
authors.initials: SM
authors.lastname: da Silveira Duarte
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, UNIFAL-MG, Alfenas, MG, Brazil. Electronic address: mritar11@yahoo.com.br.
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Rodrigues
mesh_terms: D000818:Animals; D002176:Candida albicans; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology* / Q000276:immunology / Q000382:microbiology; D006442:Glycated Hemoglobin / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology*; D007155:Immunologic Factors / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D006442:Glycated Hemoglobin; D017127:Glycation End Products, Advanced; D006146:Guanidines; D007155:Immunologic Factors; D008562:Membrane Glycoproteins; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D017382:Reactive Oxygen Species; C500593:Cybb protein, rat; C004479:pimagedine
keywords: Aminoguanidine; Aminoguanidine bicarbonate (PubChem CID 164944); Candida albicans; Diabetes; Glycation of proteins; Neutrophils; Reactive Oxygen Species