Abstract 681: The Effects of a Sustained-Release N-acetylcysteine Prodrug on Vascular Inflammation in Experimental Atherosclerosis
| Autor: | Michael V. McConnell, Mitsuaki Isobe, Joshua M. Spin, Hisanori Kosuge, Yadon Arad, Toshinobu Saito |
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| Rok vydání: | 2015 |
| Předmět: |
Chemokine
Pathology medicine.medical_specialty biology business.industry Inflammation Pharmacology Prodrug medicine.disease_cause Bioavailability Proinflammatory cytokine Lesion Acetylcysteine medicine biology.protein medicine.symptom Cardiology and Cardiovascular Medicine business Oxidative stress medicine.drug |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 35 |
| ISSN: | 1524-4636 1079-5642 |
| Popis: | Background: Oxidative stress plays a key role in the development of atherosclerosis. N-acetylcysteine (NAC) has the potential to reduce oxidative stress and inflammation, but has a short half-life and low oral bioavailability. We studied a sustained-release formulation of NAC for the suppression of vascular inflammation in experimental atherosclerosis. Methods: ApoE-deficient mice (n=17) were started on a high-fat diet at the age of 7-13 weeks and given a daily oral gavage of either sustained-release NAC (n=8, 200mg/kg/mouse, total ~5040mg) or phosphate buffered saline (n=9) for 12 weeks. The sustained-release NAC formulation was an esterified prodrug called SURE-NACTM (Tiara Pharmaceuticals, Inc., Sunnyvale, CA). After 12 weeks, aortae were harvested and histology/immunohistochemistry performed. The levels of inflammatory cytokines in the plasma were evaluated using antibody-conjugated bead sets for 26 mouse cytokines and chemokines in multiplexed sandwich immunoassay format. Results: Lesion lipid area was significantly reduced in mice treated with sustained-release NAC compared to controls, for both the entire aorta and the aortic root: Lesion lipid area in entire aorta (% of total area) - 6.5±0.8% vs 13.3±1.1%, p Conclusions: A sustained-release NAC prodrug showed substantial suppression of lesion lipid area, macrophage infiltration, and inflammatory cytokines in experimental atherosclerosis. This may provide a novel daily oral therapy to reduce vascular inflammation for the prevention and treatment of atherosclerosis. |
| Databáze: | OpenAIRE |
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