Resveratrol-Loaded Lipid-Core Nanocapsules Modulate Acute Lung Inflammation and Oxidative Imbalance Induced by LPS in Mice.

Diego De Sá Coutinho,Patrícia Machado Rodrigues E Silva,Sílvia Stanisçuaski Guterres,Andressa Bernardi,Maria Talita Pacheco De Oliveira,Adriana Raffin Pohlmann,Marco Aurélio Martins

doi:10.3390/pharmaceutics13050683

Diego De Sá Coutinho, Patrícia Machado Rodrigues E Silva + Show 5 more

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https://doi.org/10.3390/pharmaceutics13050683

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Abstract

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are inflammatory and oxidative imbalance lung conditions with no successful pharmacological therapy and a high mortality rate. Resveratrol (RSV) is a plant-derived stilbene that presents anti-inflammatory and antioxidant effects. However, its therapeutic application remains limited due to its poor bioavailability, which can be solved by the use of nanocarriers. Previously, we demonstrated that nanoencapsulated RSV (RSV-LNC) pre-treatment, performed 4 h before lipopolysaccharide (LPS) stimulation in mice, increased its anti-inflammatory properties. In this study, we evaluated the anti-inflammatory and antioxidant effects, and lung distribution of RSV-LNCs administered therapeutically (6 h post LPS exposure) in a lung injury mouse model. The results showed that RSV-LNCs posttreatment improved lung function and diminished pulmonary inflammation. Moreover, RSV-LNC treatment enhanced the antioxidant catalase level together with a decrease in the oxidative biomarker in mouse lungs, which was accompanied by an increase in pulmonary Nrf2 antioxidant expression. Finally, the presence of RSV in lung tissue was significantly detected when mice received RSV-LNCs but not when they received RSV in its free form. Together, our results confirm that RSV nanoencapsulation promotes an increase in RSV bioavailability, enhancing its therapeutic effects in an LPS-induced lung injury model.

Highlights

Acute lung injury (ALI) and the most severe form of acute respiratory distress syndrome (ARDS) represent a combination of clinical signs characterized by severe inflammation and diffuse alveolar damage, which lead to alveolar edema and reduction in tissue oxygenation [1,2]
We demonstrated that RSV-lipid-core nanocapsules (LNCs) improved lung function, inhibited the influx of leukocytes and pro-inflammatory mediator levels into pulmonary tissue, and reduced lung damage and the expression of transcription factors associated with the inflammatory response
All the data reported suggest that oral treatment with polymeric nanocapsules containing RSV enhanced lung bioavailability, resulting in an increase in antiinflammatory and antioxidant effects in a murine lung injury model

Summary

Introduction

Acute lung injury (ALI) and the most severe form of acute respiratory distress syndrome (ARDS) represent a combination of clinical signs characterized by severe inflammation and diffuse alveolar damage, which lead to alveolar edema and reduction in tissue oxygenation [1,2]. Together, it results in a high mortality rate with a reduction in survivors’. Oxidative stress plays a central role in disease progression. Oxidative damage is characterized by an imbalance between

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