title: Major depression induces oxidative stress and platelet hyperaggregability.
abstract: We have previously demonstrated an impairment of intraplatelet L-arginine-nitric oxide-cGMP pathway in major depression (MD) associated to platelet dysfunction. Here, we evaluated arginase pathway and phosphodiesterase 5 (PDE5) expression in platelets, systemic and intraplatelet oxidative status in untreated MD patients, and their effects on platelet aggregation. Blood samples were collected from 22 treatment naive MD patients (31 ± 2 yr) and 27 healthy subjects (33 ± 2 yr). MD patients presented with an activation of platelet arginase II, which competes with L-arginine for the production of nitric oxide (NO). An increase in protein carbonylation, overexpression of NADPH oxidase and PDE5, an enzyme that inactivates cGMP, was observed in platelets from MD patients compared to controls. In this context, platelet hyperaggregability was found in MD patients. On the other hand, antioxidant enzymes catalase, glutathione peroxidase and superoxide dismutase activities in serum and in platelets did not differ between groups. The increased activation of intraplatelet arginase and platelet aggregability, in addition to an overexpression of PDE5 and oxidative stress may contribute to alterations in L-arginine-NO-cGMP pathway and in platelet function, and consequently to the increased thrombotic risk in MD.
authors.affiliation: Department of Pharmacology and Psychobiology, University of the State of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Monique B O
authors.initials: MB
authors.lastname: Ormonde do Carmo
authors.affiliation: Department of Pharmacology and Psychobiology, University of the State of Rio de Janeiro, Rio de Janeiro, Brazil; Department of Physiological Sciences, Federal University of the State of Rio de Janeiro, Brazil.
authors.forename: Antônio Cláudio
authors.initials: AC
authors.lastname: Mendes-Ribeiro
authors.affiliation: Department of Pharmacology and Psychobiology, University of the State of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Cristiane
authors.initials: C
authors.lastname: Matsuura
authors.affiliation: Department of Pharmacology and Psychobiology, University of the State of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Vivian L
authors.initials: VL
authors.lastname: Pinto
authors.affiliation: Department of Pharmacology and Psychobiology, University of the State of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Wanda V
authors.initials: WV
authors.lastname: Mury
authors.affiliation: Department of Pharmacology and Psychobiology, University of the State of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Nathalia O
authors.initials: NO
authors.lastname: Pinto
authors.affiliation: Department of Pharmacology and Psychobiology, University of the State of Rio de Janeiro, Rio de Janeiro, Brazil; Department of Physiological Sciences, Federal University of the State of Rio de Janeiro, Brazil.
authors.forename: Monique B
authors.initials: MB
authors.lastname: Moss
authors.affiliation: Department of Pharmacology and Psychobiology, University of the State of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Marcos Rochedo
authors.initials: MR
authors.lastname: Ferraz
authors.affiliation: Department of Pharmacology and Psychobiology, University of the State of Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: tbrunini@uerj.br.
authors.forename: Tatiana M C
authors.initials: TM
authors.lastname: Brunini
mesh_terms: D000328:Adult; D001119:Arginase / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism*; D016022:Case-Control Studies; D002374:Catalase / Q000378:metabolism; D003865:Major Depressive Disorder / Q000097:blood / Q000378:metabolism*; D005260:Female; D005979:Glutathione Peroxidase / Q000097:blood / Q000378:metabolism; D006801:Humans; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress; D058986:Phosphodiesterase 5 Inhibitors / Q000378:metabolism; D010974:Platelet Aggregation; D013482:Superoxide Dismutase / Q000097:blood / Q000378:metabolism; D055815:Young Adult
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; C477631:ARG2 protein, human; D001119:Arginase
keywords: Arginase; Major depression; Nitric oxide; Oxidative stress; Platelets