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Article

Nitric-Oxide-Releasing Dexamethasone Derivative NCX-1005 Improves Lung Function and Attenuates Inflammation in Experimental Lavage-Induced ARDS

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Biomedical Centre Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03601 Martin, Slovakia
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Department of Physiology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03601 Martin, Slovakia
*
Author to whom correspondence should be addressed.
Academic Editor: Fabiana Quaglia
Pharmaceutics 2021, 13(12), 2092; https://doi.org/10.3390/pharmaceutics13122092
Received: 2 November 2021 / Revised: 2 December 2021 / Accepted: 2 December 2021 / Published: 5 December 2021
Acute respiratory distress syndrome (ARDS) is a common complication of critical illness and remains a major source of morbidity and mortality in the intensive care unit (ICU). ARDS is characterised by diffuse lung inflammation, epithelial and endothelial deterioration, alveolar–capillary leak and oedema formation, and worsening respiratory failure. The present study aimed to investigate the anti-inflammatory activity of nitric-oxide-releasing dexamethasone derivative NCX-1005 as a potential novel drug for ARDS. Adult rabbits with lavage-induced ARDS were treated with dexamethasone i.v. (0.5 mg/kg; DEX) and nitro-dexamethasone i.v. (0.5 mg/kg, NCX-1005) or were untreated (ARDS). Controls represented healthy ventilated animals. The animals were subsequently oxygen-ventilated for an additional 4 h and respiratory parameters were recorded. Lung oedema, inflammatory cell profile in blood and bronchoalveolar lavage, levels of the cytokines (IL-1β, IL-6, IL-8, TNF-α), and oxidative damage (TBARS, 3NT) in the plasma and lung were evaluated. Nitric oxide-releasing dexamethasone derivative NCX-1005 improved lung function, reduced levels of cytokines, oxidative modifications, and lung oedema formation to similar degrees as dexamethasone. Only NCX-1005 prevented the migration of neutrophils into the lungs compared to dexamethasone. In conclusion, the nitric oxide-releasing dexamethasone derivative NCX-1005 has the potential to be effective drug with anti-inflammatory effect in experimental ARDS. View Full-Text
Keywords: NCX-1005; nitro-steroid; nitric oxide donor; dexamethasone; ARDS; animal model; lung function; inflammation; oxidative stress NCX-1005; nitro-steroid; nitric oxide donor; dexamethasone; ARDS; animal model; lung function; inflammation; oxidative stress
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MDPI and ACS Style

Kosutova, P.; Kolomaznik, M.; Calkovska, A.; Mokra, D.; Mikolka, P. Nitric-Oxide-Releasing Dexamethasone Derivative NCX-1005 Improves Lung Function and Attenuates Inflammation in Experimental Lavage-Induced ARDS. Pharmaceutics 2021, 13, 2092. https://doi.org/10.3390/pharmaceutics13122092

AMA Style

Kosutova P, Kolomaznik M, Calkovska A, Mokra D, Mikolka P. Nitric-Oxide-Releasing Dexamethasone Derivative NCX-1005 Improves Lung Function and Attenuates Inflammation in Experimental Lavage-Induced ARDS. Pharmaceutics. 2021; 13(12):2092. https://doi.org/10.3390/pharmaceutics13122092

Chicago/Turabian Style

Kosutova, Petra, Maros Kolomaznik, Andrea Calkovska, Daniela Mokra, and Pavol Mikolka. 2021. "Nitric-Oxide-Releasing Dexamethasone Derivative NCX-1005 Improves Lung Function and Attenuates Inflammation in Experimental Lavage-Induced ARDS" Pharmaceutics 13, no. 12: 2092. https://doi.org/10.3390/pharmaceutics13122092

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