Exposure to a combination of formaldehyde and DINP aggravated asthma-like pathology through oxidative stress and NF-κB activation

Several epidemiological and experimental studies indicate a positive association between exposure to formaldehyde or phthalates and allergic asthma. However, nothing is yet known about the effects of exposure to formaldehyde and phthalates together, nor the role of each on allergic asthma. Here, we investigated the effects of a combined exposure to formaldehyde and diisononyl phthalate (DINP) on asthma-like pathology in mice, and determined the underlying mechanisms implicated in NF-κB and ROS. Mice were exposed to formaldehyde and/or DINP and sensitization with OVA. The results showed that exposure to 1.0 mg/m³ formaldehyde or 20 mg/kg·d DINP slightly aggravated the airway wall remodeling, promoted the production of IgE and IgG1, and induced the occurrence of airway hyperresponsiveness (AHR). However, these pathological responses and AHR were greatly exacerbated by the combined exposure to formaldehyde and DINP. Administering melatonin to block oxidative stress, alleviated the pathological responses and AHR induced by formaldehyde and DINP, and inhibited the activation of the NF-κB and the secretion of TSLP. Blocking NF-κB with Dehydroxymethylepoxyquinimicin, inhibited the elevation of TSLP expression and Th2/Th17 cytokine secretion, and effectively alleviated the allergic asthma-like symptoms. The results suggested that exposure to both formaldehyde and DINP aggravated hypersensitivity asthma symptoms by promoting oxidative stress and activating NF-κB. These findings expand our understanding of how formaldehyde and DINP exposure affect the development of allergic asthma.