| Phthalic acid esters (PAEs) are widely used in many kinds of plastic products, in order to increase their plasticity and flexibility. Exposure to phthalates is widespread for humans almost everyday. Epidemiological studies suggest that phthalate exposure may be related to the risk of allergic dermatitis. Studies have shown that some traditional phthalate plasticizers do great harm to human health. So they are gradually replaced by some new types of phthalate plasticizer such as DIDP, which are considered to be low toxic phthalate until recently. Although the toxicity of new types of phthalate plasticizers is relatively low, it is worth our attention on the potential hazard caused by their wide application. As an environmentally friendly plasticizer, DIDP is widely used in many daily necessities, such as some toys which can be put into the mouth of children. Diet is one of the major sources of human exposure to DIDP. However, little is known about the adverse effects and underlying mechanisms of DIDP exposure on immunological diseases.To explore the effect of diisodecyl phthalate (DIDP) on atopic dermatitis, 0.5%concentration of fluorescein isothiocyanate (FITC) was used to build a mouse model of allergic dermatitis , and melatonin (MT) was used as a blocking agent of oxidative stress.Male Balb/c mice were randomly divided into seven groups: (1) saline group, (2) 200 mg/kg/d DIDP group, (3) FITC group, (4) FITC + 2 mg/kg/d DIDP group, (5) FITC + 20 mg/kg/d DIDP group, (6) FITC + 200 mg/kg/d DIDP group, (7) FITC + 200 mg/kg/d DIDP+MT group. The mice of (1) - (7) groups were given a gavage of saline or three different concentrations of DIDP and the mice of (7) group were also given a gavage of MT once a day for continuous 21 days respectively. And subsequent three times of sensitization with 0.5% FITC on day 22, 23, 28. At the last day of the experiment, all of the mice were narcotized and sacrificed for sample preparation and then a series of physiological and biochemical indexes were measured and observed. To measure the ear swelling and ear bilateral weight and observe the pathological alterations of ear tissue. To measure the levels of serum IgE、mast cell degranulation 、 Th2 cytokines IL-4 and Th1 cytokines IFN-y. To test the levels of oxidative stress and antioxidant genes expression in ear tissue. And the TSLP content and activation levels of NF-κB and STATs also should be tested. The results are as follows:1. 200 mg/kg/d DIDP alone could not lead to the symptom of allergic dermatitis but obvious oxidative damage.2. Compared with the saline group, FITC group and FITC combined with DIDP groups could lead to the results: (1) obvious ear swelling and pathological alterations of ear tissue. (2) The concentrations of Th2 cytokines IL-4 and serum IgE were significatly elevated, while Thl cytokines IFN-ycontent was steady, which showed that allergic dermatitis model was related to Th2 immune response. Besides, there was more mast cells degranulation. (3) ROS levels were elevated significantly, while GSH levels were decreased, which showed that obvious oxidative damage appeared in ear tissue.(4)The TSLP content was increased obviously.(5) The phosphorylation level of NF-κB was elevated.(6) The phosphorylation level of STATs was also elevated significantly.3. Compared with the FITC group, FITC+200 mg/kg/d DIDP group could lead to the results: (1) more obvious ear swelling and pathological alterations of ear tissue.(2)The levels of IL-4 and IgE were further elevated. And mast cells degranulation was also aggravated. (3)The ROS levels were increased significantly. (4) The TSLP content was further increased. (5) The phosphorylation level of STATs was also further elevated.4. Compared with the FITC+200 mg/kg/d DIDP group, FITC+200mg/kg/d DIDP+MT group could lead to the results: (1)The ear swelling and pathological alterations of mice were alleviated. (2) The levels of IL-4 and IgE were decreased. And there was less mast cells degranulation. (3) ROS levels were decreased significantly,while GSH levels were increased. (4)The levels of Nrf2> HO-1 and NQO-1 were increased significantly. (5) The TSLP content was decreased. (6) The phosphorylation level of NF-κB was decreased. (7) The phosphorylation level of STAT3、5、6 were also decreased significantly.Conclusions: oral DIDP exposure can aggravate allergic dermatitis in mice.Oxidative stress may be an important molecular mechanism of allergic dermatitis.Besides, DIDP in combination with FITC triggers TSLP production. Our results also suggested that DIDP exacerbated the activation of NF-kB signal pathways, with an enhancement in TSLP expression, which potentiated the activation of STATs, and finally exacerbated allergic dermatitis. The study also suggested that melatonin enhanced the expression of Nrf2, up-regulated the antioxidant genes HO-1 and NQO1, reduced the levels of oxidative stress and TSLP, and alleviated allergic dermatitis. This study can help provide theoretical basis of the toxicity research of DIDP, as well as the prevention and treatment of allergic diseases. |
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