Abstract

Allergic rhinitis (AR) is a common chronic inflammatory disease of the upper respiratory tract. Di(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer and belongs to environmental endocrine disruptors (EDCs). It can be entered the human body which is harmful to health. The relationship between DEHP and AR is still inconclusive. This study aims to investigate the effect of environmental pollutants DEHP on AR. By examining DEHP metabolites in the urine of AR patients and building an AR model. 24 BALB/c mice were used as the study subjects, and ovalbumin (OVA) and DEHP (3 mg/kg/body) were used for intragastric administration. They were divided into control group, DEHP group, OVA group and OVA + DEHP group. Examination, behavioral scoring, inflammatory factor testing, oxidative stress testing, detection of aryl hydrocarbon receptor (AhR) and signaling pathways CYP1A1 and CYP1B1 related proteins and mRNA. The concentrations of 3 metabolites of DEHP (MEHHP, MEOHP, and MEHP) in urine of AR patients were higher. And HE-staining showed that for the control group, many chronic inflammatory cell infiltration and nasal mucosal destruction were observed in the OVA + DEHP group and were more severe than the OVA group. Allergic symptom scores were obtained from sneezing, scratching, number of scratching, and nose flow. The scores of the OVA group and the OVA + DEHP group were higher than 7 points. Serum ELISA and nasal mucosal oxidative stress tests are more serious in the OVA + DEHP group. The expression of AhR protein and its mRNA was increased in the DEHP group, OVA group and OVA + DEHP group. The OVA + DEHP group was more significant in the OVA group and DEHP group. And the mRNAs of the AhR-related signaling pathways CYP1A1 and CYP1B1 were also more prominent in the OVA + DEHP group. DEHP may aggravate its inflammatory response through the AhR pathway closely related to the environment. When combined with OVA, DEHP can further aggravate the OVA-induced nasal inflammatory response and make the nasal cavity have undergone severe changes, and many inflammatory cells have infiltrated. DEHP has shown an adjuvant effect, and the AhR-related signaling pathways CYP1A1 and CYP1B1 may be critical.

Highlights

  • Allergic rhinitis (AR) is a common upper respiratory disease

  • The concentration of mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), mono2-ethyl-5-carboxypentyl phthalate (MECPP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP) and MEHP in the urine of the subjects was skewed in this study, and the differences of MEHHP, MEOHP and MEHP concentrations between AR group and NAR group were statistically significant (P < 0.05), and the MECPP concentrations were not significantly different between the two groups (P > 0.05)

  • We found that the concentrations of Di(2-Ethylhexyl) Phthalate (DEHP) metabolites MEHHP, MEOHP, and MEHP in the urine of patients with AR were significantly higher than those in the NAR group, but MECPP was not

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Summary

Introduction

Allergic rhinitis (AR) is a common upper respiratory disease. The main clinical symptoms are: paroxysmal sneezing, runny, nasal congestion and nasal itching, which may be accompanied by eye symptoms such as itching and tearing. Di(2-Ethylhexyl) Phthalate (DEHP) is a kind of EDCs, which is the most widely used and widely used plasticizer in China, and that can enter the human body through drinking, eating, skin contact and breathing, and has toxic effects on reproductive development, kidney, respiratory system, immune system and nervous s­ ystem[3,4,5]. It is closely related to allergic diseases, we hypothesize that DEHP plays a role in the AR immune regulatory network. Since the immunological characteristics of AR are based on the imbalance of CD4+ Th cell network, which is dominated by the differentiation of Th2 cells, and a study have found that the binding of AhR and its ligand Methyl 2-(1-indole-3-carbonyl)thiazole-4-carboxylate (ITE) has an important negative regulatory effect on DC cells, which in turn regulates the differentiation and function of downstream Th ­cells[13]. To understand the effect of DHEP on AR, our experiment examined DEHP metabolites in urine on AR patients and DEHP gavage method to explore the expression of inflammatory factors, oxidative stress and AhR expression in DEHP exposure alone, DEHP and OVA combined exposure, which base on AR model

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