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Article

SUL-151 Decreases Airway Neutrophilia as a Prophylactic and Therapeutic Treatment in Mice after Cigarette Smoke Exposure

1
Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The Netherlands
2
Sulfateq B.V., Admiraal de Ruyterlaan 5, 9726 GN Groningen, The Netherlands
3
Cardiovascular Regenerative Medicine, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands
4
Institute for Risk Assessment Sciences (IRAS), Utrecht University, 3584 CM Utrecht, The Netherlands
5
Nutricia Research, Department of Immunology, 3584 CT Utrecht, The Netherlands
*
Author to whom correspondence should be addressed.
Academic Editor: Javier Conde Aranda
Int. J. Mol. Sci. 2021, 22(9), 4991; https://doi.org/10.3390/ijms22094991
Received: 19 April 2021 / Revised: 1 May 2021 / Accepted: 6 May 2021 / Published: 8 May 2021
Chronic obstructive pulmonary disease (COPD) caused by cigarette smoke (CS) is featured by oxidative stress and chronic inflammation. Due to the poor efficacy of standard glucocorticoid therapy, new treatments are required. Here, we investigated whether the novel compound SUL-151 with mitoprotective properties can be used as a prophylactic and therapeutic treatment in a murine CS-induced inflammation model. SUL-151 (4 mg/kg), budesonide (500 μg/kg), or vehicle were administered via oropharyngeal instillation in this prophylactic and therapeutic treatment setting. The number of immune cells was determined in the bronchoalveolar lavage fluid (BALF). Oxidative stress response, mitochondrial adenosine triphosphate (ATP) production, and mitophagy-related proteins were measured in lung homogenates. SUL-151 significantly decreased more than 70% and 50% of CS-induced neutrophils in BALF after prophylactic and therapeutic administration, while budesonide showed no significant reduction in neutrophils. Moreover, SUL-151 prevented the CS-induced decrease in ATP and mitochondrial mtDNA and an increase in putative protein kinase 1 expression in the lung homogenates. The concentration of SUL-151 was significantly correlated with malondialdehyde level and radical scavenging activity in the lungs. SUL-151 inhibited the increased pulmonary inflammation and mitochondrial dysfunction in this CS-induced inflammation model, which implied that SUL-151 might be a promising candidate for COPD treatment. View Full-Text
Keywords: COPD; inflammation; oxidative stress; budesonide; neutrophils; SUL compound; mitochondria; PINK1; chromanol COPD; inflammation; oxidative stress; budesonide; neutrophils; SUL compound; mitochondria; PINK1; chromanol
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MDPI and ACS Style

Wang, L.; Pelgrim, C.E.; Swart, D.H.; Krenning, G.; van der Graaf, A.C.; Kraneveld, A.D.; Leusink-Muis, T.; van Ark, I.; Garssen, J.; Folkerts, G.; Braber, S. SUL-151 Decreases Airway Neutrophilia as a Prophylactic and Therapeutic Treatment in Mice after Cigarette Smoke Exposure. Int. J. Mol. Sci. 2021, 22, 4991. https://doi.org/10.3390/ijms22094991

AMA Style

Wang L, Pelgrim CE, Swart DH, Krenning G, van der Graaf AC, Kraneveld AD, Leusink-Muis T, van Ark I, Garssen J, Folkerts G, Braber S. SUL-151 Decreases Airway Neutrophilia as a Prophylactic and Therapeutic Treatment in Mice after Cigarette Smoke Exposure. International Journal of Molecular Sciences. 2021; 22(9):4991. https://doi.org/10.3390/ijms22094991

Chicago/Turabian Style

Wang, Lei, Charlotte E. Pelgrim, Daniël H. Swart, Guido Krenning, Adrianus C. van der Graaf, Aletta D. Kraneveld, Thea Leusink-Muis, Ingrid van Ark, Johan Garssen, Gert Folkerts, and Saskia Braber. 2021. "SUL-151 Decreases Airway Neutrophilia as a Prophylactic and Therapeutic Treatment in Mice after Cigarette Smoke Exposure" International Journal of Molecular Sciences 22, no. 9: 4991. https://doi.org/10.3390/ijms22094991

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