title: Reduction of oxidative stress by oral N-acetyl-L-cysteine treatment decreases plasma soluble vascular cell adhesion molecule-1 concentrations in non-obese, non-dyslipidaemic, normotensive, patients with non-insulin-dependent diabetes.
abstract: To assess in vivo effects of antioxidants on vascular cell adhesion molecule (VCAM)-1 expression, circulating soluble VCAM-1 and intraerythrocytic reduced glutathione (GSH) and GSH disulphide (GSSG) concentrations were evaluated in non-insulin-dependent diabetic patients without complications (9 men, 6 women, 48 +/- 6 years old) before and after 1 month of either oral N-acetyl-L-cysteine (1.200 mg/day) or placebo treatments, given in randomized, cross-over, double-blind fashion. Ten healthy subjects (7 men, 3 women, 52 +/- 4 years old) served as control subjects. Baseline plasma VCAM-1 concentrations were higher (p = 0.007) in non-insulin-dependent diabetic patients (707.9 +/- 52.5 ng/ml) than in control subjects (627.3 +/- 84.6 ng/ml). Intraerythrocytic GSSG content was higher (non-insulin dependent diabetic patients: 0.618 +/- 0.185 micromol/g Hb; control subjects: 0.352 +/- 0.04 micromol/g Hb, p = 0.0002), whereas intraerythrocytic GSH concentrations were lower (p = 0.001) in non-insulin dependent diabetic patients (6.0 +/- 0.7 micromol/g Hb) than in control subjects (7.1 +/- 0.5 micromol/g Hb). The mean GSH:GSSG ratio was also lower (p = 0.0001) in the first (10.9 +/- 4.5) than in the second group (20.2 +/- 1.4). Circulating VCAM-1 and intraerythrocytic GSH concentrations were negatively correlated in non-insulin diabetic patients (r = 0.605, p = 0.01). Treatment with N-acetyl-L-cysteine decreased plasma VCAM-1 (p = 0.01) and intraerythrocytic GSSG (p = 0.006) but increased GSH concentrations (p = 0.04) and the GSH:GSSG ratio (p = 0.004) in non-insulin dependent diabetic patients. Our data indicate that the vascular endothelium is activated in non-insulin dependent diabetes. Antioxidant treatment counterbalanced such endothelial activation. Thus, antioxidant agents might protect against oxidant-related upregulation of endothelial adhesion molecules and slow down the progression of vascular damage in non-insulin dependent diabetes.
authors.affiliation: Università La Sapienza, Fondazione Andrea Cesalpino, Roma, Italy.
authors.forename: G
authors.initials: G
authors.lastname: De Mattia
authors.forename: M C
authors.initials: MC
authors.lastname: Bravi
authors.forename: O
authors.initials: O
authors.lastname: Laurenti
authors.forename: M
authors.initials: M
authors.lastname: Cassone-Faldetta
authors.forename: A
authors.initials: A
authors.lastname: Proietti
authors.forename: O
authors.initials: O
authors.lastname: De Luca
authors.forename: A
authors.initials: A
authors.lastname: Armiento
authors.forename: C
authors.initials: C
authors.lastname: Ferri
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000284:Administration, Oral; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D002784:Cholesterol / Q000097:blood; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D004311:Double-Blind Method; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D005260:Female; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D019803:Glutathione Disulfide / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D012016:Reference Values; D014280:Triglycerides / Q000097:blood; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood*
chemical_list: D001786:Blood Glucose; D016166:Free Radical Scavengers; D007328:Insulin; D014280:Triglycerides; D019010:Vascular Cell Adhesion Molecule-1; D002784:Cholesterol; D019803:Glutathione Disulfide; D000111:Acetylcysteine