A Study On Inflammatory And Oxidative Injury Of Methyl Acrylate In Mice Lung Tissue

Objectives The inhalation exposure of methyl acrylate with static total enclosure cabinet to expolure the inflammatory and oxidative damage in mice lung tissue in order to provide the theoretical evidence for evaluating the inhalation toxicity of MA and protecting the exposed population group further.Methods In this paper, healthy Kunming mice were choosen from Laboratory Animal Center of Lanzhou University to probe into the acute and subcronic toxicity induced by MA uesd by the acute and subchronic toxicity test in mice. (1) The modified Karbers method was used to evaluate the acute toxic effect and calculate LC50 of inhalation exposure MA in mice. The lung and kidney tissue were selected to calculate the cardiopulmonary index and wet/dry weight ratio and observe the pathological changes with light microscopy. (2) In the subchronic toxicity test,80 healthy Kunming mice were randomly divided into 4 groups including control group and MA groups at doses of 280 mg/m3,560mg/m3 and 1120mg/m3 with inhalation exposure for two hours everyday for 30 days in a static total enclosure chamber respectively. At 31th day, mice were sacrificed in batch by cervical dislocation respectively and weigh the lung and heart to evaluate the cardiopulmonary index and wet/dry weight ratio. The right lung tissue were selected to observe the pathological changes, but the left lung tissue were used to prepare the homogenate and measure the contents of IL-6 and TNF-a with Enzyme-Linked Immunosorbent Assay(ELISA) and the index of oxidative stress effect including the levels of superoxide dismutase (SOD), glutathione (GSH), malonaldehyde(MDA) and total anti-oxidative capacity (T-AOC) with spectrophotometric assay. Meanwhile, the index of oxidative stress effect including the levels of SOD, GSH, MDA and T-AOC in liver, brain tissue were measured with same methods in the same condition. Results (1)The acute toxicity of MA in mice.①The main acute toxic effects of MA was irritant effect of respiratory tract and toxic effect of central nervous system in mice.②The LC50 of MA with inhalation exposure in mice was 11205.52 mg/m3 with Karber's method.③The acute toxicity test discovered MA inhaled in high concentrations could cause damages to lung. There were the phenomena of edema, congestion, hemorrhage and gastrointestinal flatulence in general morphous of gross anatomy of lung tissue, and invasion of inflammatory cells and cell degeneration and necrosis under light microscope.④Compared with control group, the cardiopulmonary index and lung wet/dry weight ratio in MA exposure groups showed abnormal changes (P<0.01). (2) The subchronic toxicity of MA in mice.①The main subchronic toxic effects of MA was irritant effect of respiratory tract.②Compared with control group, the weight gain in mice decreased in MA exposure groups after 7th day (P<0.05).③The general morphous of gross anatomy in lung tissue showed the extensive hemorrhage and swelling.The pathologic changes of lung tissue could be seen under light microscope such as inflammatory cell infiltration and congestion in lung mesenchyma, but edema could be seen in MA 1120 mg/m3 exposure group.④The cardiopulmonary index and lung wet/dry weight ratio didn't discover any abnormal changes in MA exposure groups comparison with control group (P>0.05).⑤Compared with control group, the levels of TNF-a and IL-6 in MA exposure groups in lung tissue increased except for TNF-a of MA 280mg/m3 group (P<0.05).⑥The activity of SOD, the content of GSH and T-AOC in lung tissue decreased in MA 1120mg/m3group (P<0.05). The content of MDA in lung tissue increased in MA 1120mg/m3 group comparison with control group (P<0.05).⑦Compared with control group, the levels of SOD, GSH and T-AOC decreased in MA 1120mg/m3 group in mice liver(P<0.05), but the content of MDA increased in MA 1120mg/m3 group in mice liver and brain(P<0.05).Conclusions The results indicated that MA with long-term exposure could emerge obviously stimulatory function of respiratory tract in mice. Pneumonocyte injury and inflammatory response induced by MA could be associated with the abnormal changes of contents of TNF-a and IL-6, and levels of SOD, GSH, T-AOC and MDA in mice lung tissure. In addition, the results suggested that inhalation MA could induce oxidative damage of liver and brain in mice.