Olmesartan Prevented Intra-articular Inflammation Induced by Zymosan in Rats

• Published in: Biological & pharmaceutical bulletin 2016/11/01, Vol.39(11), pp.1793-1801
• Main Authors: Guerra, Gerlane Coelho Bernardo, Marília Stefani Souza de Menezes, Araújo, Aurigena Antunes de, Raimundo Fernandes de Araújo Júnior, Caroline Addison Carvalho Xavier de Medeiros
• Format: Article
• Language: English
• Subjects: Alanine Transaminase - blood; Angiotensin II Type 1 Receptor Blockers - pharmacology; Angiotensin II Type 1 Receptor Blockers - therapeutic use; Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Antihypertensive Agents - pharmacology; Antihypertensive Agents - therapeutic use; Antihypertensives; Arthritis, Experimental - chemically induced; Arthritis, Experimental - drug therapy; Arthritis, Experimental - metabolism; Arthritis, Experimental - pathology; Aspartate Aminotransferases - blood; Creatinine - blood; Cyclooxygenase 2 - metabolism; Cyclooxygenase-2; Diclofenac; Glutathione - metabolism; Glutathione peroxidase; Glutathione Peroxidase - metabolism; Histopathology; Imidazoles - pharmacology; Imidazoles - therapeutic use; Immunofluorescence; Immunohistochemistry; Inflammation; Interleukin 17; Interleukin-17 - metabolism; intra-articular inflammation; Leukocyte Count; Male; Malondialdehyde; Malondialdehyde - metabolism; olmesartan; Peroxidase - metabolism; Rats; Rats, Wistar; Sodium; Superoxide dismutase; Superoxide Dismutase - metabolism; Synovial fluid; Synovial Membrane - drug effects; Synovial Membrane - metabolism; Synovial Membrane - pathology; Synovium; Tetrazoles - pharmacology; Tetrazoles - therapeutic use; Tumor necrosis factor; Tumor Necrosis Factor-alpha - metabolism; Tumors; Urea - blood; Zymosan
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b16-00296

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.