Olmesartan Prevented Intra-articular Inflammation Induced by Zymosan in Rats.
The objective of this study was to study the effect of olmesartan medoxomil (OLM), an antihypertensive drug, on intra-articular inflammation induced by zymosan (Zy) in Wistar rats. Intra-articular inflammation was induced in the right knees of rats by 1 mg Zy dissolved in saline. The animals were divided into the following groups: saline only (oral saline and intra-articular saline); Zy only (intra-articular Zy and oral saline), and intra-articular Zy and oral OLM (5, 15, or 30 mg/kg) or diclofenac sodium (SD; 100 mg/kg). Twenty-four hours after Zy injection, synovial fluid was collected for total leukocyte counts, blood was collected for biochemical measurements, and synovial tissue was collected for histopathology, immunohistochemistry, immunofluorescence and myeloperoxidase (MPO), malonaldehyde (MDA), and non-protein sulphydryl (NPSH) assays. OLM doses of 15 and 30 mg/kg had protective effects, as evidenced by improved histopathological parameters of synovium, reduced total leukocyte counts, reduced MPO and MDA levels, and increased NPSH group levels compared with the Zy group. OLM reduced immunostaining for cyclooxygenase 2, tumour necrosis factor and interleukin 17 and increased immunostaining for superoxide dismutase and glutathione peroxidase. SD produced similar results. The drugs studied caused no change in biochemical parameters of the animals. OLM showed protective effects in this model of Zy-induced intra-articular inflammation.
Post Graduation Program in Biological Sciences/Federal University of Rio Grande do Norte, Department Biophysical and Pharmacology, Federal University of Rio Grande do Norte.
Gerlane Coelho Bernardo
GC
Guerra
Marília Stefani Souza
MS
de Menezes
Aurigena Antunes
AA
de Araújo
Raimundo Fernandes
RF
de Araújo Júnior
Caroline Addison Carvalho Xavier
CA
de Medeiros
D000410:Alanine Transaminase / Q000097:blood; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001219:Aspartate Aminotransferases / Q000097:blood; D003404:Creatinine / Q000097:blood; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D020381:Interleukin-17 / Q000378:metabolism; D007958:Leukocyte Count; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014508:Urea / Q000097:blood; D015054:Zymosan
D047228:Angiotensin II Type 1 Receptor Blockers; D000893:Anti-Inflammatory Agents; D000959:Antihypertensive Agents; C515934:Il17a protein, rat; D007093:Imidazoles; D020381:Interleukin-17; D013777:Tetrazoles; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; C437965:olmesartan; D014508:Urea; D015054:Zymosan; D003404:Creatinine; D009195:Peroxidase; D005979:Glutathione Peroxidase; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D013482:Superoxide Dismutase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione