101. SUL-151 Decreases Airway Neutrophilia as a Prophylactic and Therapeutic Treatment in Mice after Cigarette Smoke Exposure
- Author
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Wang, Lei, Pelgrim, Charlotte E, Swart, Daniël H, Krenning, Guido, van der Graaf, Adrianus C, Kraneveld, Aletta D, Leusink-Muis, Thea, van Ark, Ingrid, Garssen, Johan, Folkerts, Gert, Braber, Saskia, Afd Pharmacology, Pharmacology, Groningen Institute for Organ Transplantation (GIOT), Cardiovascular Centre (CVC), Afd Pharmacology, and Pharmacology
- Subjects
0301 basic medicine ,Budesonide ,Neutrophils ,Pharmacology ,medicine.disease_cause ,Piperazines ,chemistry.chemical_compound ,0302 clinical medicine ,neutrophils ,Medicine ,oxidative stress ,Biology (General) ,Lung ,Spectroscopy ,Mice, Inbred BALB C ,COPD ,medicine.diagnostic_test ,General Medicine ,Malondialdehyde ,chromanol ,Mitochondria ,Computer Science Applications ,mitochondria ,Chemistry ,medicine.anatomical_structure ,Female ,medicine.symptom ,Bronchoalveolar Lavage Fluid ,medicine.drug ,budesonide ,QH301-705.5 ,Bronchi ,Inflammation ,Article ,Catalysis ,Cigarette Smoking ,Inorganic Chemistry ,03 medical and health sciences ,SUL compound ,Animals ,Humans ,Physical and Theoretical Chemistry ,Molecular Biology ,QD1-999 ,business.industry ,PINK1 ,Interleukin-8 ,Organic Chemistry ,Epithelial Cells ,Pneumonia ,medicine.disease ,Neutrophilia ,Disease Models, Animal ,030104 developmental biology ,Bronchoalveolar lavage ,030228 respiratory system ,chemistry ,Oxidative stress ,inflammation ,Chromanol ,business ,Protein Kinases - Abstract
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.
- Published
- 2021