Evidence of anti-inflammatory effects of pioglitazone in the murine pleurisy model induced by carrageenan.
Several studies have shown that the anti-inflammatory effect of Pioglitazone extends beyond the cardiovascular system. This study examines the anti-inflammatory effect of Pioglitazone in comparison to reference drugs (Dexamethasone and Indomethacin) in the mouse model of pleurisy induced by carrageenan which is characterized by two distinct phases (4 and 48 h) of inflammation. Pioglitazone (20 and 50 mg/kg, i.p., 0.5 h before pleurisy) inhibited both neutrophil (4 h) and mononuclears (48 h) influxes (P<0.01), but not exudation (P>0.05). While one dose of Pioglitazone was effective in inhibiting inflammation at 4 h, additional doses (10 or 20 mg/kg, i.p., 0.5 h before pleurisy induction followed by either a second dose at 24 h after the first one or two further doses at 12 h of time interval after the first one) were necessary to elicit inhibition of the second (48 h) inflammation phase. These effects were associated with a marked decrease in adenosine-deaminase (ADA) activity, tumor necrosis factor-alpha (TNF-alpha) and interleukin 1-beta (IL-1beta) levels (P<0.01). Myeloperoxidade (MPO) activity was inhibited only at 4 h (P<0.05). By contrast, reference drugs were able to inhibit all the studied inflammatory parameters (P<0.05). These results demonstrated an interesting anti-inflammatory property of this thiazolidinedione class and strengthen prior evidence that PPAR pathways constitute another important route of inflammatory process inhibition of this pleurisy model.
Fröde
Tânia Silvia
TS
Departamento de Análises Clínicas, Centro de Ciências da Saúde, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil. saleh@ccs.ufsc.br
Buss
Ziliani da Silva
Zda S
dos Reis
Gustavo Oliveira
GO
Medeiros
Yara Santos
YS
D000243:Adenosine Deaminase / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D002351:Carrageenan / Q000008:administration & dosage; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D007165:Immunosuppression Therapy; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000473:pathology; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D009195:Peroxidase / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000077205:Pioglitazone; D010998:Pleurisy / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D045162:Thiazolidinediones / Q000008:administration & dosage*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D002351:Carrageenan; D009195:Peroxidase; D000243:Adenosine Deaminase; D000077205:Pioglitazone