Effects of acute and long-term diazepam administrations on neutrophil activity: a flow cytometric study.
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.
Applied Pharmacology and Toxicology Laboratory, School of Veterinary Medicine, University of São Paulo, São Paulo, SP, Brazil.
Fábio Ribeiro
FR
da Silva
Ricardo
R
Lazzarini
Luiz Carlos
LC
de Sá-Rocha
Maria Silvia F A
MS
Morgulis
Cristina
C
de Oliveira Massoco
João
J
Palermo-Neto
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002351:Carrageenan; D002851:Chromatography, High Pressure Liquid; D003345:Corticosterone / Q000097:blood; D003975:Diazepam / Q000097:blood / Q000494:pharmacology*; D004361:Drug Tolerance; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D005434:Flow Cytometry; D018757:GABA Modulators / Q000097:blood / Q000494:pharmacology*; D058785:GABA-A Receptor Agonists; D007546:Isoquinolines / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects*; D010587:Phagocytosis / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D016897:Respiratory Burst / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D001570:Benzodiazepinones; D018757:GABA Modulators; D058785:GABA-A Receptor Agonists; D007546:Isoquinolines; D008070:Lipopolysaccharides; C028513:4'-chlorodiazepam; D002351:Carrageenan; D013755:Tetradecanoylphorbol Acetate; D003975:Diazepam; D003345:Corticosterone; C037850:PK 11195