SUL-151 Decreases Airway Neutrophilia as a Prophylactic and Therapeutic Treatment in Mice after Cigarette Smoke Exposure
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...
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2021-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/9/4991 |
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| author | Lei Wang 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 Saskia Braber |
| author_facet | Lei Wang 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 Saskia Braber |
| author_sort | Lei Wang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T11:37:47Z |
| format | Article |
| id | doaj.art-b269643808004d63aa639888e988f1ba |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T11:37:47Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b269643808004d63aa639888e988f1ba2023-11-21T18:46:13ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-05-01229499110.3390/ijms22094991SUL-151 Decreases Airway Neutrophilia as a Prophylactic and Therapeutic Treatment in Mice after Cigarette Smoke ExposureLei Wang0Charlotte E. Pelgrim1Daniël H. Swart2Guido Krenning3Adrianus C. van der Graaf4Aletta D. Kraneveld5Thea Leusink-Muis6Ingrid van Ark7Johan Garssen8Gert Folkerts9Saskia Braber10Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The NetherlandsDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The NetherlandsSulfateq B.V., Admiraal de Ruyterlaan 5, 9726 GN Groningen, The NetherlandsSulfateq B.V., Admiraal de Ruyterlaan 5, 9726 GN Groningen, The NetherlandsSulfateq B.V., Admiraal de Ruyterlaan 5, 9726 GN Groningen, The NetherlandsDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The NetherlandsDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The NetherlandsDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The NetherlandsDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The NetherlandsDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The NetherlandsDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The NetherlandsChronic 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.https://www.mdpi.com/1422-0067/22/9/4991COPDinflammationoxidative stressbudesonideneutrophilsSUL compound |
| spellingShingle | Lei Wang 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 Saskia Braber SUL-151 Decreases Airway Neutrophilia as a Prophylactic and Therapeutic Treatment in Mice after Cigarette Smoke Exposure International Journal of Molecular Sciences COPD inflammation oxidative stress budesonide neutrophils SUL compound |
| title | SUL-151 Decreases Airway Neutrophilia as a Prophylactic and Therapeutic Treatment in Mice after Cigarette Smoke Exposure |
| title_full | SUL-151 Decreases Airway Neutrophilia as a Prophylactic and Therapeutic Treatment in Mice after Cigarette Smoke Exposure |
| title_fullStr | SUL-151 Decreases Airway Neutrophilia as a Prophylactic and Therapeutic Treatment in Mice after Cigarette Smoke Exposure |
| title_full_unstemmed | SUL-151 Decreases Airway Neutrophilia as a Prophylactic and Therapeutic Treatment in Mice after Cigarette Smoke Exposure |
| title_short | SUL-151 Decreases Airway Neutrophilia as a Prophylactic and Therapeutic Treatment in Mice after Cigarette Smoke Exposure |
| title_sort | sul 151 decreases airway neutrophilia as a prophylactic and therapeutic treatment in mice after cigarette smoke exposure |
| topic | COPD inflammation oxidative stress budesonide neutrophils SUL compound |
| url | https://www.mdpi.com/1422-0067/22/9/4991 |
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