Olmesartan decreases IL-1β and TNF-α levels; downregulates MMP-2, MMP-9, COX-2, and RANKL; and upregulates OPG in experimental periodontitis

Abstract

The objective of this study is to investigate the participation of inflammatory and oxidative stress mediators and the effects on the expression of matrix metalloproteinase (MMP)-2, MMP-9, and receptor activator of NF-κB ligand (RANKL)/receptor activator of NF-κB (RANK)/osteoprotegerin (OPG) pathway in the response to treatment with olmesartan, an angiotensin II type 1 receptor blocker. Male Wistar albino rats were randomly divided into five groups of ten rats each: (1) non-ligature with water, (2) ligature with water, (3) ligature with 1 mg/kg olmesartan, (4) ligature with 6 mg/kg olmesartan, and (5) ligature with 10 mg/kg olmesartan. All groups were treated with olmesartan or the vehicle by gavage daily for 10 days. Following the treatment course, the periodontal tissue of the animals was analyzed by histopathology and immunohistochemistry to determine the expression of cyclooxygenase-2 (COX-2), MMP-2, MMP-9, and members of the RANKL/RANK/OPG pathway and by ELISA and spectroscopic assay to determine the levels of interleukin (IL)-1β, IL-10, tumor necrosis factor (TNF)-α, myeloperoxidase (MPO), malonaldehyde (MDA), and glutathione. The concentrations of MPO and MDA were reduced in the group that received 6 mg/kg olmesartan (p < 0.05). In addition, the group that was treated with 6 mg/kg olmesartan showed a decreased level of IL-1β (p < 0.05), and all doses of olmesartan resulted in decreased levels of TNF-α. Furthermore, treatment with 6 mg/kg olmesartan led to downregulation of the expression of COX-2, MMP-2, MMP-9, RANKL, and RANK and to upregulation of the expression of OPG. These findings suggest that 6 mg/kg olmesartan reduces the inflammatory process and bone loss by downregulating MMPs and RANKL in osteoblasts and by upregulating OPG.

Azilsartan Increases Levels of IL-10, Down-Regulates MMP-2, MMP-9, RANKL/RANK, Cathepsin K and Up-Regulates OPG in an Experimental Periodontitis Model

“…In this study, azilsartan treatment produced some results than previous studies by our group using other antihypertensives. Telmisartan and Olmesartan significantly reduced pro-inflammatory cytokines such as IL-1β and TNF-α, which resulted in significant preservation of bone in periodontal disease [2], [3]. In the periodontium, the activation of IL-1β and TNF-α is known to stimulate the degradation of connective tissue matrix, the activation of osteoclasts, and the resorption of bone [17], [18].…”

In a Methotrexate-Induced Model of Intestinal Mucositis, Olmesartan Reduced Inflammation and Induced Enteropathy Characterized by Severe Diarrhea, Weight Loss, and Reduced Sucrose Activity

“…12) In particular, olmesartan (OLME) is an angiotensin II type 1 receptor (AT1) blocker that inhibits levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β, thereby mediating anti-inflammatory activity. 13) In the present study, the effects of OLME on a MTX-induced gastrointestinal mucositis model established in rats were examined. Animals Albino, male Wistar rats (180-330 g; Bioterio Department of Biophysical and Pharmacology) were maintained in a temperature-and humidity-controlled environment with a 12-h light/dark cycle (lights on at 6 a.m.).…”

Olmesartan Prevented Intra-articular Inflammation Induced by Zymosan in Rats

“…46) Additional studies have confirmed the anti-inflammatory activity of OLM in other models of inflammation. 19,31,47) Our results are of importance, given that RA is associated with an increased risk of CVD, and that hypertension is a prevalent risk factor for CVD in patients with RA. Thus, the use of OLM in patients with RA can bring dual benefits, due to the drug's anti-inflammatory and antihypertensive properties.…”

“…30) In this study and in other experimental models of inflammation, OLM reduced the expression of COX-2, which could result in tissue protection. 19,31) COX-2 is an enzyme induced in inflammatory processes; it is involved in the synthesis of prostaglandins and inflammatory cytokines, which promote local inflammation and tissue damage. Some authors have suggested that COX-2 expression in the synovial fibroblasts of patients with RA contributes to increased expression of inflammatory cytokines in cartilage matrix.…”