| Due to the excellent chemical properties of dibutyl phthalate (DBP), it was currently widely used in the fields of plastics, lubricants, resin solvent, adhesive, cosmetic, pesticide carrier, printing ink as one kind of plasticizers. DBP is non-covalent binding with the molecular of material through hydrogen bond and Van der Waals force, and is easily released into the environment in the process of production, use and waste, and then enter the human body via a variety of ways to cause harm to humans. Previous studies suggested that DBP was a kind of environmental endocrine disruptor, which acted as homologous estrogen, anti-androgen and thyroid hormone disrupting compounds to cause toxicity. Additionally, DBP also has the neural developmental toxicity, immune-toxicity and reproductive toxicity. The prevalence of allergic diseases around the world, especially the developed countries, has been increasing dramatically in recent years. However, the types and quantities of allergens in the environment not changed so much. Epidemiological and experimental studies showed that the involvement of phthalate esters (PAEs) to this increase in allergic diseases, and continued exposure to PAEs could increase the incidence and severity of allergen-induced asthma by similar immune adjuvant effect.In the present study, we established a T-helper 2 (Th2) type murine asthma model to explore whether it could aggravate the asthma-like related symptoms by a long-term oral exposure route of DBP, and sought the potential molecular mechanism. Specific-pathogen-free (SPF) male Balb/c mice were randomly divided into 5 groups: saline control group, DBP exposure group, ovalbumin (OVA) sensitized group, OVA and DBP combined group, melatonin (MT) treated group. Each mouse was given saline or DBP (10 mg/kg/day) to lavage calculated by body mass from 0 to 27 days. Mice of OVA and combined groups were sensitized by intraperitioneal (i.p.) and subcutaneous (s.c.) injection of OVA to initiate the immune response on day 6,13,20 and 27. MT-treated micewere received the same sensitization and challenge routine with combined group and was given subcutaneously at body weight half an hour before each sensitization of OVA. All mice were exposed to an aerosol of 1% OVA or saline on seven successive days (days 28～34) for 30 min to induce the asthma-like symptoms.24 h after the last challenge, we determined the lung function, histopathological examination, inflammatory cell counts and interlukin-4 (IL-4) and interferon-γ (IFN-γ) secretion in bronchoalveolar lavage fluid (BALF), the content of total immunoglobulin E (T-IgE) in serum and the level of oxidative stress to examine the aggravation effect of DBP and the possible mechanism.Results indicated that all biomarkers of DBP exposure group showed no significance compared with the control group, which suggested that DBP could not initiate the immune response of mice due tothe small molecule property. An exacerbation of Th2-type response of lungs was appeared in OVA sensitized groupand mainly as follows:the higher of content of IL-4 and T-IgE, enhancement of airway hyper responsiveness (AHR), severity of airway remodeling exacerbation, pulmonary fibrosis and mucous hyper-secretion, increased numbers of various inflammatory cells in BALF. On the contrary, Thl-type response was decreased and mainly as follows: the decline of the content of IFN-γ and ratio of IFN-γ/TL-4. Additionally, all effects were significantly different compared with control group, which indicated that the establishment of the asthma model was successful, and the balance of Thl/Th2 was broken and shift to Th2-type cell populations. What’s more, the higher of the level of oxidative stress between OVA sensitized group and control showed oxidative stress was one of the pathogenesis of asthma. In combined group, long-term exposure to DBP deteriorated the mice asthma-like symptoms to some extent. However, we did not see a significant difference compared with OVA sensitized group except inspiratory resistance of AHR. It suggested that DBP had a less pronounced adjuvant effect and the effect of enhancing asthma-like symptoms was not mediated via an oxidative stress mechanism. The administration of antioxidant MT significantly reversed all these effects by combined exposure.In conclusion, long-term exposure to DBP can aggravated allergen-induced allergic diseases by its weak adjuvant effect, and it was not mediated via an oxidative stress mechanism. In order to decrease the incidence of allergic diseases, the atopy and asthma-suffering people should avoid excessive exposure to DBP and far away from those places with abundant PAEs. |
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