A Primary Study On Oxidative Damage And Mechanism Of Asthma Induced By PAEs

Phthalates(PAEs), a group of synthetic chemicals with a wide spectrum of industrial and commercial applications, can be used as plasticizers and solvents in many products. Because of non-bound covalently to plastics, phthalates can be easily released to the environment, and cause potential health problems. Human as well as animals can be exposed to these ubiquitous compounds through oral exposure (via phthalate-contaminated food, water and in children through mouthing of toys and teethers), dermal exposure (via cosmetics and other personal care products), inhalational exposure (via volatilization of PVC, nail polish, hair spray, and other phthalate-containing products), and iatrogenic exposure (via blood bags, injection syringes, intravenous canullas, catheters and plastic parts of dialysers). Many of the findings reported in human and laboratory animals were consistent with the reproductive and developmental toxicity, liver toxicity, immune toxicity and neurotoxicity which had been demonstrated for several phthalates. Biomarkers of exposure are preferred methods of exposure assessment, and urine is the preferred matrix for phthalate determination in humans. Because of rapid metabolism, urinary metabolite levels are typically measured than levels of the parent compound found in other media. Further, by measuring metabolites, the risk of accidental contamination during collection, storage, and analysis is greatly reduced. In order to assess phthalates'risks to human health, epidemiology and animal studies can be combined.Therefore, the aims of this study were:①Assessing the levels of phthalates exposure by measuring metabolites in urine.②Illustrating the effects of phthalates on the acute oxidative damage by detecting the activity of ROS, the contents of MDA and the coefficient of DPC in the liver cells of Wistar rats in vitro.③Analyzing the possible mechanism of asthma induced by phthalates. My results are as follow.1. By measuring phthalate metabolites in students'urine,93.3% MEHP,56.7% MBP and 70% MBzP can be detected, and the average levels of metabolites were:MEHP= 29.0μg/L, MBP=176.4μg/L, MBzP=690.1μg/L.2. Phthalates can cause the oxidative damage to the liver cells of rats. The probably mechanism is that phthalate exposure enhanced the levels of ROS, while the overfull ROS could consume the antioxidant enzymes, causing lipid peroxidation, and bringing the damages of DNA.3. In order to explore the possible mechanism of asthma induced by phthalates, we divided 24 Balb/C mice into 4 groups (n=6) randomly, the mice were exposured to 0,0.1, 1,10 mg/kg/d DEHP for 14d, then we applied RT-PCR to assess GSNOR, TSLP, NGF, TRPV1 mRNA expression levels in mice lung tissues. The results showed that DEHP could up-regulate the expression effects of GSNOR, TSLP and NGF mRNA in lung tissues, suggesting that DEHP may induce asthma via GSNOR, TSLP, and NGF pathways.