Mediating roles of oxidative stress and nuclear factor kappa B signaling in benzyl butyl phthalate-aggravated allergic asthma.

Abstract

It has been proposed that benzyl butyl phthalate (BBP) exposure raises the risk of allergic asthma, but current research evidence is not sufficient to fully support this claim. Examining the function and mechanism of BBP in exacerbating allergic asthma was the goal of this investigation. To create an allergic asthma model, 90 male Balb/c mice were randomly split into 6 groups, comprising of saline (control); OVA; 10 BBP + OVA; 100 BBP + OVA; 250 BBP + OVA; and 1250 BBP + OVA. To investigate if BBP makes allergic asthma worse in mice given OVA, we first examined lung histological sections and airway hyperresponsiveness (AHR). Second, we investigated oxidative stress, the signaling pathway of nuclear factor kappa B (NF-κB), and the inflammatory factors that are downstream of it to explore mechanism of BBP exacerbating allergic asthma.The results showed that, the enhanced pause (Penh) value in BBP + OVA group was remarkably greater in contrast to OVA group, indicating increased AHR, whereas worsening airway remodeling was observed in lung tissue slices. Both Penh and airway remodeling worsened as the BBP dose increased. In addition, exposure to BBP + OVA resulted in enhanced levels of markers related to the NF-κB signaling pathway and oxidative stress, decreases in Th1 inflammatory cytokine levels, and increases in Th2/Th17 inflammatory cytokine levels. Combined exposure to OVA and BBP worsened AHR and airway wall remodeling, and these impacts were correlated with oxidative stress and elevated secretion of IgE, NF-κB biomarkers, and Th1/Th2/Th17 cytokines. Therefore, we suggest that the primary mechanisms by which BBP aggravates allergic asthma through Th1/Th2/Th17 cytokine modulation include the NF-κB pathway and oxidative stress. It may be a potential drug target for the treatment of allergic asthma.