Effects of arsenic trioxide (As(2)O(3)) on airway remodeling in a murine model of bronchial asthma.

We investigated the effects of arsenic trioxide (As(2)O(3)) as a possible approach for preventing airway remodeling in a murine model of bronchial asthma induced by ovalbumin (OVA) challenge. Forty Balb/c mice were randomly assigned to 1 of 4 groups (10 mice/group) as follows: controls (challenged with sterile saline inhalation only); OVA-challenged, no treatment; OVA-challenged, treated with dexamethasone; and OVA-challenged, treated with As(2)O(3). All mice were sensitized by intraperitoneal injection with 10% OVA at 2 weeks prior to saline or OVA inhalation challenge. Challenges were for 8 weeks. After OVA challenge, typical asthma-like morphology changes in the bronchi and lung tissues were observed by hematoxylin-eosin staining and pulmonary function indices were reduced compared with controls. Changes in pulmonary indices and lung tissues were similar in the dexamethasone and As(2)O(3) groups and were in between those of the untreated and control groups. Compared with the untreated group, transforming growth factor β1, vascular endothelial growth factor, and matrix metalloproteinase-9 protein levels and mRNA expression were decreased in lung tissues of the dexamethasone and As(2)O(3) groups. Our results suggest that steroids and As(2)O(3) can inhibit airway remodeling in chronic asthma by mechanisms related to inhibiting the expression of the 3 aforementioned mediators.