| The problems of chemical indoor pollution caused by decorative materials and organic life daily necessities are receiving amounts of attention. The current health evaluation of indoor air pollution mainly depends on pollutant concentrations, Health Questionnaire, and toxicity effect of single pollutant. Little information is available on the health evaluation indices of mixed pollutants of indoor air. Animal models are established to evaluate the oxidation damage, genetic toxicity, immunological toxicity, respiratory system toxicity and molecular mechanisms of pollutants in indoor air, and to find biomarkers, provide scientific basis for the revision and perfection of the related indoor air quality standards.(1) A short-term VOCs inhalation model (formaldehyde, benzene, toluene, and xylene) was established, yield the following five groups:0(control) and4different doses of VOCs mixture. The concentrations of VOCs mixture corresponded to10,30,50, and100times of indoor air quality standard in China and mice were exposed for consecutive10days at2h/day. It was observed that short-term VOCs inhalation could cause oxidative damage in lung and liver, affect immune system by inhibiting CD8+CD3+(%) and increasing CD4+CD3+(%) in spleen, increase the levels of IL-6, NT-3, and the number of inflammatory cells in bronchoalveolar lavage fluid (BALF), decrease substance P in BALF, affect haematological parameters. There were positive correlations and dose-effect relationships between Reactive oxygen species (ROS), Malondialdehyde (MDA) levels in lung and liver, CD4+CD3+(%), CD4+CD3+/CD8+CD3+in spleen cell and VOCs concentrations. There were negative correlations or dose-effect relationships between Glutathione peroxidase (GSH-Px) in liver, Glutathione (GSH) in lung, CD8+CD3+(%) in spleen cell and VOCs concentrations. These results showed that ROS in lung and liver, GSH-Px in liver, CD4+CD3+(%), CD8+CD3+(%), CD4+CD3+/CD8+CD3+in spleen cell could be used as sensitive biological effect markers under short-term VOCs mixture condition. NO signaling pathways might induce airway inflammatory in short term VOCs exposure mice and the airway inflammatory response may be modulated by neurological signaling.(2) Eight miRNAs were used to profile the expression of lung miRNAs and IL-8level in BALF was measured by ELISA. Male Kunming mice exposed to filtered air (0) and three types of VOCs mixture (formaldehyde, benzene, toluene, and xylene) treated air.The concentrations of VOCs mixture corresponded to30,50, and100times of indoor air quality standard in China and mice were exposed for consecutive10days at2h/day. The results revealed that VOCs exposure resulted in significantly expanded distribution of miRNA expression levels in treated groups compared to controls, down regulation of662miRNAs and up regulation of96miRNAs in group1, down regulation of592miRNAs and up regulation of68miRNAs in group2, down regulation of11miRNAs and up regulation of18miRNAs in group3. Six miRNAs were simultaneously upregulated and1miRNA was simultaneously downregulated in three treated groups. With the increasing of VOCs concentration, the expressions of mmu-miR-494, mmu-miR-744and mmu-miR-335-5p were gradually decreased. Functional Annotation analysis of the predicted miRNA transcript targets revealed that VOCs exposure potentially altered signaling pathways associated with cancer and inflammatory. IL-8levels increased significantly relative to control mice (p<0.01). It was showed that mmu-miR-5105could be used as a sensitive biological marker under short-term VOCs mixture condition, dose-dependent relationships were found between mmu-miR-494, mmu-miR-744, mmu-miR-335-5p and VOCs concentrations, VOCs exposure might potentially lead to the initiation of cancer and inflammatory diseases. The result of IL-8showed VOCs exposure induced airway inflammatory.(3) A low level of long-term VOCs inhalation model (formaldehyde, benzene, toluene, and xylene) was established, yield the following five groups:0(control) and4different doses of VOCs mixture. The concentrations of VOCs mixture corresponded to1/2,1,5, and10times of indoor air quality standard in China and mice were exposed for consecutive90days at2h/day. It was found that VOCs inhalation of low levels could cause oxidative damage in lung, increase significantly IL-8, eotaxin, NGF, and the number of various types of leukocytes in BALF, IgE in serum, disturb the relative balance between Th1and Th2cytokines in BALF, inhibit CD8+CD3+(%) in spleen, affect haematological parameters. With increasing VOCs dosages, Total antioxidative capacity (T-AOC), GSH-Px levels in lung were gradually decreased, while CD4+CD3+/CD8+CD3+in spleen cell,1L-4levels in BALF, tail moment (TM) of liver cell in comet assay were increased. It was suggested T-AOC levels in lung, CD4+CD3+/CD8+CD3+in spleen cell, IL-4levels in BALF, tail moment (TM) of liver cell in comet assay could be used as sensitive biological effect markers under long-term VOCs mixture condition, Sub-chronic VOCs-induced inflammatory response was at least partly caused by release of the ROS and mediators from the activated eosinophils, neutrophils, alveolar macrophages (AMs) and epithelial cells.(4) A "particulate matter (PM)+Staphylococcus aureus (SA)+high level of short-term VOCs (formaldehyde, benzene, toluene, and xylene) inhalation" model was established, yield the following seven groups:0(control), PM exposure group, SA exposure group,"PM+SA’ exposure group,"PM+SA+VOCs (10times of indoor air quality standard)"exposure group,"PM+SA+VOCs (50times of indoor air quality standard)"exposure group,"PM+SA+VOCs (100times of indoor air quality standard)"exposure group. Mice were exposed for consecutive10days at2h/day. It was found that "PM+SA+VOCs" exposure could affect normal growth level, oxidative stress in lung, inflammatory factors in BALF and8-hydroxy-2’-deoxyguanosine (8-OHdG) in serum from mice, toxicity effects of "PM+SA+VOCs" were higher than those of single component. These results suggested T-AOC in lung, IL-4, IL-8in BALF could be used as sensitive biological effect markers under "PM+SA+VOCs" exposure condition. |
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