Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Department of Anatomy and Histology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Pharm Biol. 2020 Dec;58(1):107-115. doi: 10.1080/13880209.2019.1710218.
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. This study investigated the protective effects of ascorbic acid in combination with calcitriol on airway remodelling in ovalbumin (OVA)-induced chronic asthma. 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). 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, = 0.02) and IgE (58.74 ± 0.43 vs. 45.78 ± 2.05 ng/mL, = 0.003) as well as the reduction of goblet hyperplasia and subepithelial fibrosis (5 vs. 1 score, = 0.001 and 5 vs. 2 score, = 0.001, respectively). 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.
气道重塑是哮喘最棘手的问题之一。根据氧化应激和炎症在气道重塑中的关键作用,推测抗坏血酸和钙三醇具有有益作用。然而,抗氧化剂的联合使用可能对哮喘治疗更有效。本研究探讨了抗坏血酸联合钙三醇对卵清蛋白(OVA)诱导的慢性哮喘气道重塑的保护作用。BALB/c 小鼠分为七组:(1)对照组;(2)哮喘组;(3)无效 C 组(口服 39mg/kg 抗坏血酸);(4)无效 D 组(腹腔内注射 1.5μg/kg 钙三醇);(5)有效 C 组(口服 130mg/kg 抗坏血酸);(6)有效 D 组(腹腔内注射 5μg/kg 钙三醇);(7)联合组(口服 39mg/kg 抗坏血酸+腹腔内注射 1.5μg/kg 钙三醇)。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,在每次激发前 30 分钟给予维生素(每周三次,连续 8 周)。与哮喘组相比,联合使用无效剂量的抗坏血酸和钙三醇可降低白细胞介素-13(IL-13)水平(50.5±1.85 与 42.13±0.37 pg/mL, = 0.02)和 IgE 水平(58.74±0.43 与 45.78±2.05 ng/mL, = 0.003),减少杯状细胞增生和上皮下纤维化(5 与 1 分, = 0.001 和 5 与 2 分, = 0.001)。联合使用无效剂量的抗坏血酸和钙三醇可改善气道重塑,这可能是通过减轻氧化应激和炎症的附加作用实现的。本研究为进一步研究和临床应用抗坏血酸和钙三醇提供了科学依据,并可推广到更广泛的药理学研究。