ABSTRACT
Statins are hypocholesterolemic drugs that are prescribed for patients with an increased risk of cardiovascular and cerebrovascular complications. Ezetimibe has an atheroprotective activity through inhibition of the expression of vascular adhesion molecule-I and vascular CD14, a marker of the infiltration of mononuclear leukocytes. Ezetimibe reduces the amount of chemoattractant protein-1 that is available for monocytes and macrophages and alters the activity of nuclear factor κB in leukocytes. The mechanisms of action of statins complement those of ezetimibe. Previous studies have demonstrated that the combination of statins and ezetimibe has beneficial effects, including antiinflammatory activity. The present study evaluated the effects of monotherapy with ezetimibe and simvastatin compared with ezetimibe + simvastatin combined on the evolution of the inflammatory response in a rat model of Complete Freund's Adjuvant-induced arthritis. The animals were treated with 10 mg/kg ezetimibe, 40 mg/kg simvastatin, or 10 mg/kg ezetimibe + 40 mg/kg simvastatin for 1, 7, 14, or 28 days. We analyzed leukocyte rolling behavior, leukocyte adhesion to the endothelium, the number of leukocytes that were recruited to the knee joint cavity, and the concentration of cytokines that are involved in the inflammatory response. The data were analyzed using paired t tests or analysis of variance followed by Bonferroni post hoc test. The treatments reduced leukocyte rolling behavior and leukocyte adhesion. The monotherapies did not change the number of leukocytes that were recruited to the knee joint cavity, whereas the ezetimibe + simvastatin combination significantly reduced this parameter. The treatments reduced the levels of proinflammatory cytokines and increased the levels of the antiinflammatory cytokine IL-10, indicating antiinflammatory properties of these drugs in this experimental model of inflammation.
Subject(s)
Arthritis, Experimental/drug therapy , Ezetimibe/pharmacology , Inflammation/drug therapy , Simvastatin/pharmacology , Animals , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Arthritis, Experimental/immunology , Arthritis, Experimental/pathology , Cell Adhesion/drug effects , Cytokines/drug effects , Cytokines/metabolism , Drug Therapy, Combination/methods , Ezetimibe/administration & dosage , Knee Joint/pathology , Leukocyte Rolling/drug effects , Leukocytes/metabolism , Rats , Simvastatin/administration & dosageABSTRACT
PURPOSE: The aim of this study was to evaluate the effect of Pogostemon cablin essential oil (PEO) on leukocyte behavior in the inflammatory response. METHODS AND RESULTS: PEO was analyzed using Gas Chromatography/Mass Spectrometry (GC/SM) and Nuclear Magnetic Resonance Spectroscopy (NMR) methods and showed predominance of patchoulol (38.50%), α-bulnesene (20.37%), α-guaiene (12.31%), seychellene (8.33%) and α-patchoulene (4.91%). PEO at concentrations of 1, 3, 10, 30, 60 and 90µg/ml reduced the in vitro neutrophil chemotaxis toward fMLP, and at concentrations of 3 and 10µg/ml, increased the phagocytic activity of neutrophils. Topical application of PEO in high concentrations promoted an increase of ear edema and myeloperoxidase (MPO) activity. However, the oral treatment with 100, 200 and 300mg/kg reduced leukocyte recruitment, nitric oxide (NO) production, and rolling and adherent leukocyte number in the microcirculation. CONCLUSION: PEO affects the leukocyte behavior, and the mechanism proposed of PEO seems to be, at least in part, involving the participation of NO and pro-inflammatory cytokines.
Subject(s)
Inflammation/pathology , Leukocytes/cytology , Sesquiterpenes/pharmacology , Acute Disease , Administration, Topical , Animals , Cell Adhesion/drug effects , Cell Survival/drug effects , Chemotaxis/drug effects , Edema/pathology , Exudates and Transudates , Gas Chromatography-Mass Spectrometry , Leukocyte Count , Leukocyte Rolling/drug effects , Leukocytes/drug effects , Male , Mice , Nitric Oxide/metabolism , Peritonitis/pathology , Peroxidase/metabolism , Phagocytosis/drug effects , Pogostemon , Sesquiterpenes/administration & dosage , ZymosanABSTRACT
OBJECTIVE: To identify whether Canova medication changes TNF-α and IL-10 serum levels in mice infected with Trypanosoma cruzi Y strain. METHODS: Animals were divided into five groups: non-treated infected animals (I); benznidazole-treated infected animals (Bz; 100 mg/kg body weight, single daily dose by gavage); Canova medication (CM) treated infected animals (CM; 0.2 mL/animal, single daily dose by gavage); benznidazole- and Canova medication-treated infected animals with the above-mentioned dose (Bz+CM); and non-infected animals (C). TNF-α and IL-10 levels were determined in serum aliquots after 4, 7, 10, 13, and 29 days of infection. An ELISA technique was employed with R&D System Inc. antibody pairs. RESULTS: A high increase in TNF-α and IL-10 levels occurred in the infected and CM-treated groups within the treatment employed on the 10th day after infection, coupled with a IL-10 decrease on the 13th day after infection when compared with the other experimental groups. CONCLUSIONS: CM may change the balance between plasma cytokine levels (TNF-α and IL-10) in mice infected with Y strain T. cruzi, with important consequences leading towards a more severe infection.
