Adjuvant effect of di-(2-ethylhexyl) phthalate on asthma-like pathological changes in ovalbumin-immunised rats

Abstract

Pollution of phthalates, including di-(2-ethylhexyl)phthalate (DEHP), is widespread because of their use in plastics and other daily consumer products. Epidemiological studies have shown that the largest source of general population exposure to DEHP is on dietary. Studies have suggested an association between exposure to phthalate plasticisers, and increased prevalence of asthma. To investigate the adjuvant effect of DEHP on asthmatic pathological changes in ovalbumin-immunised rat model. Wistar rats were randomly divided into five groups (eight rats of each group): (1) saline; (2) ovalbumin (OVA); (3) OVA'DEHP 0.7mg ×kg (1 ×d (1 ; (4) OVA'DEHP 70 mg ×kg (1 × d (1 ; and (5) DEHP 70 mg ×kg (1 ×d (1 . DEHP treatment groups which were administered to 0.7 mg and 70 mg DEHP/kg/d by gastric gavage for 30d before and during the process of OVA immunisation or saline treatment. The in vivo pulmonary function analysis, bronchoalveolar lavage (BAL) fluid collection and section histological observation were conducted. DEHP exposure could significantly increase airway hyperresponsiveness, airway remolding, and eosinophil infiltration in the OVA-immunised rats. But the DEHP exposure alone group does not show significant airway structural change and inflammatory cell infiltration, compared with control group. DEHP administered by gastric gavage play an adjuvant effect on respiratory systems in ovalbumin-immunised rat model.

Phthalate exposure and asthma in children

“…Inflammatory cells in bronchoalveolar lavage fluid (BALF) and airway irritation and hyper‐reactivity were analysed in four of the reports in Table 2 (Larsen et al ., 2004, 2007; Hansen et al ., 2007; Yang et al ., 2008). Larsen et al (2007) identified increased levels of eosinophils, lymphocytes and neutrophils but not macrophages in BALF after 14 weeks with repeated inhalation of DEHP.…”

“…In agreement with a recruitment of eosinophils, increased levels of lymphocytic production of IL‐5 were seen in the same two studies. Late inflammatory states and remodelling typical for asthma in humans have generally not been addressed, with the exception of a study by Yang et al . (2008) who in addition to increased levels of leukocytes in BALF after p.o.…”

The adjuvant effect induced by di-(2-ethylhexyl) phthalate (DEHP) is mediated through oxidative stress in a mouse model of asthma

“…related to asthma and other allergic symptoms in children in a separate epidemiological investigation (Bornehag et al, 2004). On the other hand, the adjuvant effect of DEHP was shown when it was co-exposed with ovalbumin (OVA) in rats asthma model at a dose of 70 mg/kg/day by gavage or a murine asthma model at a dose of 3000 lg/kg/day by gavage (Guo et al, 2012;Yang et al, 2008). It is highly possible that DEHP might act as an adjuvant in its contribution to the increased incidence of asthma and allergies in the developed world.…”

Pulmonary Toxicity and Adjuvant Effect of Di-(2-exylhexyl) Phthalate in Ovalbumin-Immunized BALB/c Mice

“…Larsen et al used a long-term inhalation model with DEHP and reported modulating effect on IgG1 response as well as inflammatory markers [20] . Ourselves have reported on DEHP promoting inflammatory responses in DEHP treated OVA-immunized rats [21] . However, in the studies by Larsen et al [17] , [18] immunosuppression was also seen after injection of high doses of MEHP, not DEHP.…”