Abstract
Context Airway remodelling is one of the most refractory problems in asthma. According to the critical roles of oxidative stress and inflammation in airway remodelling, it is supposed that ascorbic acid and calcitriol have beneficial effects. However, a combination of antioxidants may be more effective for asthma therapy. Objective This study investigated the protective effects of ascorbic acid in combination with calcitriol on airway remodelling in ovalbumin (OVA)-induced chronic asthma. Materials and methods BALB/c mice were assigned into seven groups: (1) Control; (2) Asthma; (3) Ineffective C (orally 39 mg/kg ascorbic acid); (4) Ineffective D (intraperitoneally 1.5 μg/kg calcitriol); (5) Effective C (orally 130 mg/kg ascorbic acid); (6) Effective D (intraperitoneally 5 μg/kg calcitriol); (7) Combination (orally 39 mg/kg ascorbic acid + intraperitoneally 1.5 μg/kg calcitriol). All animals were sensitized and challenged with OVA except in the control group (normal saline). In all treatment groups, mice were administrated vitamins 30 min before each challenge (three times per week for 8 consecutive weeks). Results In comparison with the asthma group, co-administration of ineffective doses of ascorbic acid and calcitriol led to the decreased levels of IL-13 (50.5 ± 1.85 vs. 42.13 ± 0.37 pg/mL, p = 0.02) and IgE (58.74 ± 0.43 vs. 45.78 ± 2.05 ng/mL, p = 0.003) as well as the reduction of goblet hyperplasia and subepithelial fibrosis (5 vs. 1 score, p = 0.001 and 5 vs. 2 score, p = 0.001, respectively). Discussion and conclusions Combination of ascorbic acid with calcitriol in ineffective doses improves airway remodelling due to additive effects possibly through reduction of oxidative stress and inflammation. This study provides a scientific basis for further research and clinical applications of ascorbic acid and calcitriol and can be generalized to the broader pharmacological studies.
Highlights
Asthma, a chronic obstructive lung disease, is characterized by the recurrent episodic symptoms including chest tightness and shortness of breath (Horak et al 2016)
There were no significant differences in IL-13 levels in the groups of ascorbic acid and calcitriol in ineffective doses compared to the asthma group (47.93 ± 0.29 vs. 50.5 ± 1.85 pg/mL and 48.14 ± 0.47 vs. 50.5 ± 1.85 pg/mL, respectively) (Figure 2)
There were no significant differences in immunoglobulin E (IgE) levels in the groups of ascorbic acid and calcitriol in ineffective doses compared to the asthma group (56.64 ± 1.82 vs. 58.74 ± 0.43 ng/mL and 57.13 ± 1.29 vs. 58.74 ± 0.43 ng/mL, respectively) (Figure 3)
Summary
A chronic obstructive lung disease, is characterized by the recurrent episodic symptoms including chest tightness and shortness of breath (Horak et al 2016). This disorder affects approximately 20% of the population worldwide and exerts considerable economic burdens for either patients or healthcare systems (Ellwood et al 2017; Nunes et al 2017). Asthma is characterized by elevated levels of T helper (Th)-2 cytokines (e.g., interleukin (IL)-13) and immunoglobulin E (IgE) as well as inflammation (Russell and Brightling 2017). Another important characteristic of asthma is airway remodelling (i.e., goblet cell hyperplasia and subepithelial fibrosis) resulting in irreversible loss of lung function (Fahy 2015). Antioxidant agents may be effective in the prevention of asthma remodelling
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