PMID- 23146878
OWN - NLM
STAT- MEDLINE
DCOM- 20130806
LR  - 20131121
IS  - 1423-0313 (Electronic)
IS  - 0031-7012 (Linking)
VI  - 91
IP  - 1-2
DP  - 2013
TI  - Novel anti-inflammatory effects of doxazosin in rodent models of inflammation.
PG  - 29-34
LID - 10.1159/000343762 [doi]
AB  - BACKGROUND: Doxazosin is an alpha(1)-adrenergic receptor antagonist for the treatment 
      of high blood pressure and benign prostatic hyperplasia. Peripheral alpha-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-alpha 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.
CI  - Copyright (c) 2012 S. Karger AG, Basel.
FAU - Tung, David
AU  - Tung D
AD  - BioMed Valley Discoveries, Kansas City, MO 64111, USA. dtung@biomed-valley.com
FAU - Ciallella, John
AU  - Ciallella J
FAU - Cheung, Peter H
AU  - Cheung PH
FAU - Saha, Saurabh
AU  - Saha S
LA  - eng
PT  - Journal Article
DEP - 20121109
PL  - Switzerland
TA  - Pharmacology
JT  - Pharmacology
JID - 0152016
RN  - 0 (Adrenergic alpha-1 Receptor Antagonists)
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Thioglycolates)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - NW1291F1W8 (Doxazosin)
SB  - IM
MH  - Adrenergic alpha-1 Receptor Antagonists/pharmacology/*therapeutic use
MH  - Animals
MH  - Anti-Inflammatory Agents/pharmacology/*therapeutic use
MH  - Chemokine CCL2/immunology
MH  - Disease Models, Animal
MH  - Doxazosin/pharmacology/*therapeutic use
MH  - Erythrocytes/immunology
MH  - Hypersensitivity, Delayed/*drug therapy/pathology
MH  - Inflammation/chemically induced/*drug therapy/immunology
MH  - Lipopolysaccharides
MH  - Male
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Peritonitis/chemically induced/*drug therapy/immunology
MH  - Sheep
MH  - Thioglycolates
MH  - Tumor Necrosis Factor-alpha/immunology
EDAT- 2012/11/14 06:00
MHDA- 2013/08/07 06:00
CRDT- 2012/11/14 06:00
PHST- 2012/08/06 00:00 [received]
PHST- 2012/09/24 00:00 [accepted]
PHST- 2012/11/14 06:00 [entrez]
PHST- 2012/11/14 06:00 [pubmed]
PHST- 2013/08/07 06:00 [medline]
AID - 000343762 [pii]
AID - 10.1159/000343762 [doi]
PST - ppublish
SO  - Pharmacology. 2013;91(1-2):29-34. doi: 10.1159/000343762. Epub 2012 Nov 9.