Study On Effects Of Typical Atmospheric Fine Particulate Matter And Intervention Mechanism Of Astaxanthin

Atmospheric particulate matter(Particulate Matter,PM),derived from fossil fuel combustion,industrial emissions and natural sources,has a significant impact on the ecological environment and living organisms.The International Agency for Research on Cancer(IARC)has classified PM as a human carcinogen.Diesel exhaust particulate matter(DPM)and biomass burning particulate matter(BB PM)are typical man-made and natural sources of PM,respectively.DPM and BB PM enter human life with traffic,industrial development,changes in climate seasons,and undergo varying degrees of aging over time,making significant changes in their toxic effects.Due to the rich organic and inorganic components in DPM and BB PM,their effects and mechanisms of toxicity are extremely complex.Currently,there is a lack of effective intervention measures.Astaxanthin(AST),as a typical natural antioxidant,has significant effects in the prevention and control of pollutants.The objective of this study is to explore the toxic effects and intervention strategies of PM with different sources and aging time,as well as to clarify the physicochemical and biological mechanisms of AST in inhibiting PM toxicity.This research provides a new experimental basis for AST in particle pollutant toxicity intervention and related disease prevention.The results of this study are as follows:1.Toxic effects of DPM and BB PM from different trees(pine,cypress,camphor trees)on target cells and mice.The results of the study showed that the cyto/genotoxicity of DPM and BB PM varied with concentration,source and aging time.Among them,DPM caused concentration-dependent cytotoxicity and genotoxicity in BEAS-2B and J774A.1 cells,respectively.The in vitro toxicity of BB PM from pines and cypresses changed slightly with the prolongation of aging time.The cell viability of fresh particles after exposure was below 60%,and the aged particles at different times showed different degrees of cyto/genotoxicity.The toxicity of aged BB PM from camphor trees was much higher than that of nearly non-toxic fresh BB PM,and the genotoxicity increased to 3.9 times that of the control group.DPM was used as a representative PM to conduct in vivo experiments in mice.The results showed that both acute(1 week)and subacute(2 weeks)exposure to DPM-induced increased levels of inflammatory factors such as interleukin 6(IL-6)and tumor necrosis factor alpha(TNFα)in mice and adverse effects such as lung injury and fibrosis.2.Antagonism of AST on the toxicity of DPM and BB PM.The results showed that,compared with other typical antagonists(vitamin C,vitamin E and sodium tanshinone IIA silate),AST had a stronger intervention effect on DPM-induced cyto/genotoxicity,and it was determined that AST also had corresponding antagonistic effects on BB PM toxicity from different sources and aging times.The antagonism of AST in vitro can significantly reduce the typical PM-induced cyto/genotoxicity,especially the expression of γ-H2AX induced by DPM to 1.19±0.27 times that of the control.Secondly,in animal experiments,it was found that feeding AST for 1 week can effectively alleviate the systemic inflammation level and target organ damage induced by DPM acute exposure.In addition,the inclusion of AST with hydroxypropyl-βcyclodextrin(HP-β-CD)enabled the drug to be delivered by tracheal infusion,and the antagonistic effect of low concentration was similar to that of high concentration feeding AST.3.Mechanism of AST antagonizing the toxicity of particulate pollutants.The research results showed that,on the one hand,AST can directly act on the cell membrane,stabilize the phospholipid bilayer,reduce fluidity,limit the process of DPM entering the cell and intracellular accumulation,and directly reduce the adverse effects of a large amount of DPM and attachments on target cells and lung tissue.On the other hand,AST can also directly eliminate the cellular oxidative stress caused by DPM,and at the same time protect the mitochondrial membrane potential from the attack of DPM and free radicals(ROS),fully exerting its antioxidant effect.Through the above in vitro and in vivo data,this study found that the toxic effects of two typical PM,DPM and BB PM,are related to the exposure dose and particle type,and clarified the antagonism and regulation mechanism of AST on the toxicity of PM.It also provides an important experimental basis for the in-depth understanding of the toxicological mechanism of the health hazards of atmospheric fine particles from different sources and expanding the toxicity intervention strategies of natural small molecules.