Effect of bosentan on the production of proinflammatory cytokines in a rat model of emphysema

Abstract

Endothelin (ET) receptor antagonists have been developed to produce a reduction of ET related effects in various diseases, as well as in animal models of airway inflammation. We aimed to investigate the anti-inflammatory potential of bosentan on a rat model of emphysema. Thirty Wistar male rats were classified as control group (group 1), intratracheally (i.t.) instilled with saline, treated with vehicle solution; elastase group (group 2), i.t. instilled with porcine pancreatic elastase (PPE), treated with vehicle solution; and PPE+bosentan group (group 3), i.t. instilled with PPE, treated with bosentan. The levels of TNF-α, IL-1β, IL-6, and IL-8 in bronchoalveolar lavage fluid (BALF) and lung tissue, cell counts in BALF, and histologic analysis of all groups were evaluated. Neutrophile granulocytes (NG) and alveolar macrophages (AM) were increased more in group 2 than in group 1 (P ＜ 0.001, P = 0.04, respectively). Compared with group 2, neutrophil granulocyte (NG) and alveolar macrophages (AM) counts were decreased in group 3 (P ＜ 0.001). Histological examination confirmed a diffuse neutrophilic inflammation and irregular alveolar air space enlargement in group 2. Treatment with bosentan partially reduced the enlarged lung volumes. Compared with group 1, the BALF levels of TNF-α and IL-6, and the lung tissue levels of IL-1β, IL-6, and IL-8 were increased in group 2 (P = 0.028, P = 0.005, P = 0.001, P = 0.019, P ＜ 0.001, respectively). The TNF-α and IL-8 levels of BALF (P = 0.007, P = 0.001, respectively), and the TNF-α, IL-1β, IL-6, and the IL-8 levels of lung tissue (P = 0.031, P = 0.017, P = 0.007, P ＜ 0.001) were decreased in group 3 compared to group 2. In conclusion, bosentan decreased the inflammatory response by reducing numbers of inflammatory cells and proinflammatory cytokines.

Comparison of reducing effect on lung injury of dexamethasone and bosentan in acute lung injury: an experimental study

“…A previous study demonstrated that bosentan treatment significantly reduced the production of reactive oxygen species by PMN during acute lung inflammation [29]. Another study demonstrated diminished levels of the pro-inflammatory cytokines TNFα, interleukin-1, interleukin-6 and interleukin-8 in rat pulmonary tissue following bosentan treatment of induced emphysema [30]. Both doses of bosentan used in the current study demonstrated pronounced reduction of lung injury.…”

Endothelin-1 and its role in the pathogenesis of infectious diseases

“…Experimental evidence suggests that this indeed, might be the case. For example, Gamze et al [128] reported that the ET A /ET B blocker bosentan significantly reduced the concentration of pro-inflammatory cytokines in a rat model of emphysema. More recently, Trabold et al [129] reported that bosentan reduced the oxidative burst in the lung in an acid-aspiration rat model.…”

The Hypolipidemic Effect of Dalbergia odorifera T. C. Chen Leaf Extract on Hyperlipidemic Rats and Its Mechanism Investigation Based on Network Pharmacology

“…Inflammation also plays a crucial role in the initiation and progression of hyperlipidemia. It is regulated by proinflammatory mediators and cytokines, including IL-1 β , IL-6, IL-18, and TNF- α [ 50 ]. In our study, D. odorifera leaf extract had an anti-inflammatory effect in hyperlipidemic rats.…”