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.

中文翻译：

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抗坏血酸和骨化三醇组合对卵清蛋白诱导的慢性哮喘气道重塑的保护作用

摘要背景：气道重塑是哮喘中最难治的问题之一。根据氧化应激和炎症在气道重塑中的关键作用，认为抗坏血酸和骨化三醇具有有益作用。然而，抗氧化剂的组合可能对哮喘治疗更有效。目的：本研究调查了抗坏血酸联合骨化三醇对卵清蛋白（OVA）诱导的慢性哮喘气道重塑的保护作用。材料和方法：BALB/c 小鼠分为七组：（1）对照组；(2) 哮喘；（3）无效C（口服39mg/kg抗坏血酸）；（4）无效D（腹腔注射1.5μg/kg骨化三醇）；（5）有效C（口服130mg/kg抗坏血酸）；(6) 有效 D（腹腔注射 5 μg/kg 骨化三醇）；(7) 组合（口服 39 mg/kg 抗坏血酸 + 腹膜内 1.5 μg/kg 骨化三醇）。除对照组（生理盐水）外，所有动物均用 OVA 致敏和激发。在所有治疗组中，小鼠在每次攻击前 30 分钟服用维生素（每周 3 次，连续 8 周）。结果：与哮喘组相比，同时服用无效剂量的抗坏血酸和骨化三醇导致 IL-13（50.5 ± 1.85 vs. 42.13 ± 0.37 pg/mL，p = 0.02）和 IgE（58.74 ± 0.43 与 45.78 ± 2.05 ng/mL，p = 0.003）以及杯状增生和上皮下纤维化的减少（分别为 5 对 1 分，p = 0.001 和 5 对 2 分，p = 0.001）。讨论和结论：无效剂量的抗坏血酸与骨化三醇的组合由于可能通过减少氧化应激和炎症的累加效应而改善气道重塑。本研究为抗坏血酸和骨化三醇的进一步研究和临床应用提供了科学依据，并可推广到更广泛的药理学研究。