Effects of acute and long-term diazepam administrations on neutrophil activity: a flow cytometric study

• Published in: European journal of pharmacology Vol. 478; no. 2; pp. 97 - 104
• Main Authors: da Silva, Fábio Ribeiro, Lazzarini, Ricardo, de Sá-Rocha, Luiz Carlos, Morgulis, Maria Silvia F.A., de Oliveira Massoco, Cristina, Palermo-Neto, João
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 08.10.2003; Elsevier
• Subjects: Animals; Benzodiazepinones - pharmacology; Biological and medical sciences; Carrageenan; Chromatography, High Pressure Liquid; Corticosterone; Corticosterone - blood; Diazepam; Diazepam - blood; Diazepam - pharmacology; Drug Tolerance; Edema - chemically induced; Edema - prevention & control; Flow Cytometry; GABA Modulators - blood; GABA Modulators - pharmacology; GABA-A Receptor Agonists; Isoquinolines - pharmacology; Lipopolysaccharides - pharmacology; Male; Medical sciences; Neutrophil; Neutrophil Infiltration - drug effects; Neutrophils - drug effects; Oxidative burst; Peripheral benzodiazepine receptor; Phagocytosis - drug effects; Pharmacology. Drug treatments; Rats; Rats, Wistar; Respiratory Burst - drug effects; Tetradecanoylphorbol Acetate - pharmacology; Tolerance development; Flow cytometry; Peripheral benzodiazepine receptor; Corticosterone; Oxidative burst; Tolerance development; Neutrophil; Diazepam; Steroid hormone; Psychotropic; Tolerance; Hypnotic; Anticonvulsant; Glucocorticoid; Long term; Tranquillizer; Adrenal hormone; Development; Benzodiazepine derivatives
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2003.08.046

This study analyzed the effects of acute and long-term diazepam treatments on rat peripheral blood neutrophil activity and cortisol serum levels. Rats were acutely and long-term (21 days, once daily) treated with diazepam (10 mg/kg) or its vehicle (1.0 ml/kg). Blood was collected 1 h after treatments for flow cytometric analysis of neutrophil oxidative burst and phagocytosis. Corticosterone and diazepam concentrations were also determined. Results showed that: (1) both diazepam treatments increased lipopolysaccharide (LPS) and phorbol myristate acetate (PMA)-induced neutrophil oxidative burst; (2) the increase in oxidative burst after Staphylococcus aureus induction in acutely treated animals was higher than that observed after long-term treatment; (3) phagocytosis is increased by acute diazepam treatment and decreased by a long-term regimen; (4) acute, but not long-term, diazepam treatment increased corticosterone levels; (5) diazepam plasmatic levels after acute and long-term treatments were not different. These results indicate the development of tolerance to diazepam effects on corticosterone serum levels but not on neutrophil activity.