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Dexamethasone attenuates grain sorghum dust extract-induced increase in macromolecular efflux in vivo
S R Akhter1, H Ikezaki, X P Gao
1Department of Medicine, University of Illinois at Chicago, and West Side Department of Veterans Affairs Medical Center, Chicago, Illinois 60612, USA.
Abstract:
The purpose of this study was to determine whether dexamethasone attenuates grain sorghum dust extract-induced increase in macromolecular efflux from the in situ hamster cheek pouch and, if so, whether this response is specific. By using intravital microscopy, we found that an aqueous extract of grain sorghum dust elicited significant, concentration-dependent leaky site formation and increase in clearance of FITC-labeled dextran (FITC-dextran; mol mass, 70 kDa) from the in situ hamster cheek pouch (P < 0.05). This response was significantly attenuated by dexamethasone (10 mg/kg iv). Dexamethasone also attenuated substance P-induced leaky site formation and increase in clearance of FITC-dextran from the cheek pouch but had no significant effects on adenosine-induced responses. Dexamethasone had no significant effects on arteriolar diameter in the cheek pouch. On balance, these data indicate that dexamethasone attenuates grain sorghum dust extract- and substance P-induced increases in macromolecular efflux from the in situ hamster cheek pouch in a specific fashion.
Insights
Dexamethasone effectively reduces macromolecular leakage in hamster cheek pouches caused by grain sorghum dust extract. This anti-inflammatory effect is specific, targeting dust extract and substance P, but not adenosine responses.
Area of Science:
- Pharmacology
- Inflammation Research
- Microcirculation Studies
Background:
- Grain sorghum dust exposure can induce inflammation and increased vascular permeability.
- Macromolecular efflux is a key indicator of vascular leakage during inflammatory processes.
- Dexamethasone is a potent anti-inflammatory corticosteroid.
Purpose of the Study:
- To investigate if dexamethasone can reduce macromolecular efflux induced by grain sorghum dust extract.
- To determine the specificity of dexamethasone's effect on vascular permeability.
- To assess the impact of dexamethasone on microvascular responses in the hamster cheek pouch model.
Main Methods:
- Intravital microscopy was employed to visualize and quantify vascular changes.
- Aqueous extract of grain sorghum dust was used to induce inflammation in the hamster cheek pouch.
- Fluorescein isothiocyanate-labeled dextran (FITC-dextran) was used to measure macromolecular clearance.
- Dexamethasone's effects were tested against dust extract, substance P, and adenosine-induced responses.
Main Results:
- Grain sorghum dust extract caused a significant, dose-dependent increase in leaky site formation and FITC-dextran clearance.
- Dexamethasone significantly attenuated the dust extract-induced increase in macromolecular efflux.
- Dexamethasone also reduced substance P-induced leakage but did not affect adenosine-induced responses, indicating specificity.
- No significant changes in arteriolar diameter were observed with dexamethasone treatment.
Conclusions:
- Dexamethasone specifically attenuates grain sorghum dust extract-induced increases in macromolecular efflux.
- The findings suggest a specific anti-inflammatory mechanism of dexamethasone in this model.
- Dexamethasone's ability to reduce vascular leakage highlights its potential therapeutic role in dust-induced inflammation.