Novel Anti-Inflammatory Effects of Doxazosin in Rodent Models of Inflammation

Abstract

Background: Doxazosin is an α₁-adrenergic receptor antagonist for the treatment of high blood pressure and benign prostatic hyperplasia. Peripheral α-adrenergic receptors have been implicated in inflammation. Aim: To examine the anti-inflammatory effects of doxazosin in rodent models of inflammation. Method: The anti-inflammatory properties of doxazosin were investigated in 4 models. In all studies, drug treatment was administered 15 min prior to challenge. In the lipopolysaccharide (LPS)-induced systemic inflammation model, LPS was injected systemically at 0.25 mg/kg. At 90 min after challenge, blood samples were collected for analysis. In the LPS-induced pulmonary inflammation model, LPS was instilled intranasally. Four hours after challenge, the lungs were harvested for monocyte chemoattractant protein-1 (MCP-1) analysis. In a delayed-type hypersensitivity model, the mice were injected intravenously with sheep red blood cells, and rechallenged in the left footpad 7 days later. Drug treatment was given on day 6 and 7 just prior to the rechallenge. The thickness of hind footpads was measured at 15 min after rechallenge. In the thioglycollate-induced peritoneal monocyte infiltration model, mice were challenged with 3% thioglycollate, and 2 h later peritoneal lavage fluid was collected for MCP-1 analysis. Results: In animals challenged systemically and intranasally with LPS, doxazosin inhibited TNF-α and MCP-1 production, respectively. In the delayed-type hypersensitivity model, footpad swelling was inhibited by doxazosin. Doxazosin decreased the level of MCP-1 release in the peritoneal cavity of thioglycollate-stimulated animals, though this effect was not statistically significant. Conclusion: This is the first set of studies that reports the novel anti-inflammatory effects of doxazosin.

2-phenylethynesulfonamide Prevents Induction of Pro-inflammatory Factors and Attenuates LPS-induced Liver Injury by Targeting NHE1-Hsp70 Complex in Mice

“…6–8-week old mice were randomly divided into four groups. 0.25 mg/kg body weight (BW) of LPS was selected to induce inflammation according to previous studies [18], [19]. In saline and LPS-treated groups, mice were injected intraperitoneally with 100 µL of saline and 0.25 mg/kg LPS in 100 µL of saline.…”

Modulation of α‐adrenoceptor signalling protects photoreceptors after retinal detachment by inhibiting oxidative stress and inflammation

“…Several proinflammatory cytokines, including CCL2, IL‐1β and TNF‐α, were induced in the subretinal fluid obtained from human eyes with RD (unpublished observations of the authors) and have previously been reported to contribute to the pathogenesis of photoreceptor death after RD (Nakazawa et al ., ; Nakazawa et al ., ; Kataoka et al ., ). Moreover, different types of ARs have been shown to be implicated in inflammatory responses within various injury models (Tung et al ., ; Way et al ., ). Thus, we next evaluated the roles of α 1 ‐ and α 2 ‐adrenoceptors in the RD‐induced up‐regulation of proinflammatory cytokines.…”

“…For all these treatments, the vehicle was 20% DMSO. The doses of the drugs were based on previous studies (Haruta et al, 2009;Yanpallewar et al, 2010;O'Neil et al, 2013;Tung et al, 2013;Way et al, 2015;Zhang et al, 2015).…”

Up-regulation of cutaneous α1-adrenoceptors after a burn

“…mediators [49,50] and pain [21], and subtype-selective a 1 -AR antagonists inhibit uncomfortable symptoms in patients with benign prostatic hyperplasia [51]. Thus, the effects of applying these agents after acute burns should be further explored.…”