Olmesartan medoxomil self-microemulsifying drug delivery system reverses apoptosis and improves cell adhesion in trinitrobenzene sulfonic acid-induced colitis in rats

Abstract

Olmesartan medoxomil (OM) is an angiotensin receptor blocker. This study aimed to investigate the effects of OM self-microemulsifying drug delivery system (OMS) in trinitrobenzene sulfonic acid (TNBS)-induced acute colitis in rats. Besides two control groups, five TNBS-colitic-treated groups ( n = 8) were given orally sulfasalazine (100 mg/kg/day), low and high doses of OM (3.0 and 10.0 mg/kg/day) (OML and OMH) and of OMS (OMSL and OMSH) for seven days. A colitis activity score was calculated. The colon was examined macroscopically. Colonic levels of myeloperoxidase, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), malondialdehyde, and reduced glutathione were measured. Plasma and colonic olmesartan levels were measured. Colonic sections were subjected to hematoxylin and eosin staining and immunohistochemical staining for E-cadherin, caspase-3, and matrix metalloproteinase-9 (MMP-9). Protein expression of E-cadherin, Bcl-2 associated X protein (Bax), and B-cell lymphoma 2 (Bcl-2), and cleaved caspase-3 by Western blot was done. TNBS-colitic rats showed increased colonic myeloperoxidase, TNF-α, IL-6, and malondialdehyde, decreased colonic glutathione, histopathological, immunohistochemical, and protein expression alterations. OMS, compared with OM, dose-dependently achieved higher colonic free olmesartan concentration, showed better anti-inflammatory, antioxidant, and anti-apoptotic effects, improved intestinal barrier, and decreased mucolytic activity. OMS more effectively up-regulated the reduced Bcl-2, Bcl-2/Bax ratio, and E-cadherin expression, and down-regulated the overexpressed Bax, cleaved caspase-3, and MMP-9. OMSL exerted effects comparable to OMH. Sulfasalazine exerted maximal colonic protective effects and almost completely reversed colonic damage, and OMSH showed nearly similar effects with non-significant differences in-between or compared with the normal control group. In conclusion, OMS could be a potential additive treatment for Crohn's disease colitis.

Heterogeneity in protocols and outcomes to study the effect of renin‐angiotensin system blockers in inflammatory bowel disease: A systematic review

“…All studies reported at least one of the following scoring systems to evaluate disease activity: DAI, MaS or histologic assessment. Seventeen out of 35 studies used DAI to evaluate the experimental model [14, 22, 23, 26–28, 30, 31, 38, 39, 42, 47–52], 17/35 studies used MaS [28, 30, 32, 34, 36, 37, 40, 41, 44–47, 50–54] and 34/35 studies used a histologic score [14, 22–26, 28–54]. Six out of the 35 studies used the three scoring systems [28, 30, 47, 50–52], 11/35 used MaS and histologic assessment [22, 32, 34, 36, 37, 40, 41, 44–46, 54] and 10/35 used DAI and histologic assessment [14, 22, 23, 26, 31, 38, 39, 42, 48, 49].…”

Nanotechnology‐Based Strategies for Extended‐Release Delivery of Angiotensin Receptor Blockers (ARBs): A Comprehensive Review

“…Disease activity scores were significantly reduced due to OMS, indicating its potential in managing Crohn's disease colitis (Figure 8). [196] Thakkar and colleagues developed OLM nanosuspensions for improved solubility using the media milling approach. The nanosuspension delivery resulted in increased permeation rates, about double the amount diffused through the biological membrane.…”

“…Western blot analysis of E-cadherin expression, Bcl-2 associated X protein (Bax), Bcl-2, and cleaved caspase-3. Reprinted from [196] under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/ 4.0/). The nanosuspension and pure drug permeability coefficients were determined to be 0.72×10 À 8 cm 2 /s and 0.18×10 À 8 cm 2 /s, respectively.…”

“…Western blot analysis of E‐cadherin expression, Bcl‐2 associated X protein (Bax), Bcl‐2, and cleaved caspase‐3. Reprinted from [196] under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/).…”

“…Disease activity scores were significantly reduced due to OMS, indicating its potential in managing Crohn's disease colitis (Figure 8). [196] …”