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Role of Doxofylline, Low Dose Theophylline, and Dexamethasone in Mice (BALB/C) Model of Corticosteroid Resistant Asthma: A Comparative Study.
- Source :
-
Annals of clinical and laboratory science [Ann Clin Lab Sci] 2024 May; Vol. 54 (3), pp. 313-325. - Publication Year :
- 2024
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Abstract
- Objective: This study was designed to determine the comparative efficacy of Doxofylline (DOXO) compared to low-dose theophylline (LDT) in treating corticosteroid-resistant asthma.<br />Methods: This study was conducted on 56 adult BALB/C mice aged six to eight weeks old with an average weight of 20-25 g. They were divided into seven groups: control group, ovalbumin (OVA)+lipopolysaccharide (LPS) group, OVA+LPS+dexamethasone (DEXA) group, OVA+LPS+LDT group, OVA+LPS+ group, OVA+LPS+DEXA+LDT group, and OVA +LPS+DEXA+DOXO group. All mice were administered IP DOXO+DEXA. All the doses were administrated one day before the first challenge and lasted for five consecutive days after one hour of the OVA challenge until sacrificed. Lung biochemical parameters, including interleukin (IL)-2, IL-4, IL-8, IL-10, and IL-17 levels, were measured using enzyme-linked immunosorbent assay (ELISA). In addition, Histone deacetylase (HDAC) activity and lung histological analysis were also performed. Furthermore, the glucocorticoid receptor was measured by nexttec™.<br />Results: The OVA+LPS group exhibited significantly ( p <0.05) elevated levels of interleukin (IL)-2, IL-4, IL-8, IL-10, and IL-17 compared to controls, indicative of airway inflammation. Moreover, OVA+LPS induction significantly ( p <0.05) increased the levels of Interferon-gamma (IFN- γ ), NF[Formula: see text]B, Tumor Necrosis Factor (TNF α ), and Immunoglobulin E (IgE) parameters, indicating severe inflammation and immune response and successfully induced the disease model. Meanwhile, LDT and DOXO in conjunction with DEXA, further augmented HDAC2 activity compared to DEXA alone. Similarly, the administration of LDT increased the expression of GR by 64.5% (23.72±0.34), while DOXO increased the expression of GR by 94.10% (27.99±0.15), which restores it back to control. Furthermore, according to Hematoxylin and eosin (H&E) stained sections, the DOXO group exhibited a slight improvement in these histopathological features, suggesting a modest therapeutic effect. Masson's Trichrome staining showed a slightly improved patchy collagen deposition within alveolar spaces in intra-alveolar and interstitial inflammatory cell accumulation in DOXO group, and the combination of these drugs (DEXA+LDT group) improved collagen deposition moderately within alveolar spaces in intra-alveolar and interstitial inflammatory cell accumulation. Overall, treatment with DOXO, LDT alone, and with DEXA combination led to reductions in cytokine levels, with DOXO and LDT showing significant ( p <0.05) efficacy to DEXA used alone, which showed non-significant ( p >0.05) efficacy.<br />Conclusions: Doxofylline and LDT were found to be effective therapeutic agents when used alone or in combination with Dexamethasone. However, randomized controlled trials are required to evaluate its further efficacy.<br /> (© 2024 by the Association of Clinical Scientists, Inc.)
- Subjects :
- Animals
Mice
Adrenal Cortex Hormones pharmacology
Adrenal Cortex Hormones therapeutic use
Cytokines metabolism
Drug Resistance drug effects
Lung drug effects
Lung pathology
Lung metabolism
Ovalbumin
Receptors, Glucocorticoid metabolism
Histone Deacetylases metabolism
Lipopolysaccharides pharmacology
Theophylline pharmacology
Theophylline analogs & derivatives
Theophylline administration & dosage
Asthma drug therapy
Asthma pathology
Mice, Inbred BALB C
Dexamethasone pharmacology
Dexamethasone administration & dosage
Disease Models, Animal
Subjects
Details
- Language :
- English
- ISSN :
- 1550-8080
- Volume :
- 54
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Annals of clinical and laboratory science
- Publication Type :
- Academic Journal
- Accession number :
- 39048174