Targeted Metabolomics Analysis And Toxic Intervention Of Dietary Acrylamide Based On Relationship Between Internal And External Exposure

The acrylamide related food safety issues have raised wide concern all over the world since a large amount of acrylamide in thermally processing foods was discovered in 2002.In recent years,the research focus on acrylamide has gradually shifted from in vitro studies to in vivo studies.The research on the exposure level of acrylamide in vivo,risk estimation method,protection pathway and control has become the focus and difficulty of the research on acrylamide in vivo by scientists in related fields.Here we systematically by building at the cellular assessment method of acrylamide toxicity,founded upon level of animals found the key to affect the metabolism of acrylamide loci and pathways by means of high resolution mass spectrometry,and finally verified by population exposure and intervention trial acrylamide levels of markers in the body change,the influence of the system and deeply analyzes the under the intervention of catechin acrylamide exposure to changes in vivo.We established Lan Xi as a middle-and old-aged community residents' queue and predominantly college students from Zhejiang University queue.24 hours recall,1 week recall and food frequency questionnaire were investigating about acrylamide in food processing pollutants exposure levels in both queues.At the same time,urine and blood samples were collected to provide sufficient samples for the biomarker detection method of acrylamide established by the research group,so as to pave the way for establishing the correlation mechanism between internal and external exposure of acrylamide.After comparing the dietary habits and characteristic data of the two populations,the exposure level of college students was about 0.691 ?g/kg bw/day,which belonged to the highly exposed population,while the exposure level of community residents was about 0.183 ?g/kg bw/day.The main reasons for the differences in acrylamide exposure between the two populations are different consumption of Fried and baked foods,different dietary habits and cooking methods.Later,college students will be the focus.Based on the group previously for catechin,and bamboo leaves flavonoids antioxidants in vitro inhibition of acrylamide performances,think from the Angle of nutrition,toxicology,looking for protection sites in the body,the ester type catechins-table gallic acid,catechin gallic acid ester(EGCG)and non-ester catechin,epicatechin(EC)and water-soluble bamboo antioxidants(AOB-w)intervention acrylamide in vivo metabolism and chemical protection effect.Studies have shown that catechins can effectively control the apoptosis induction of Hep G2 cells by acrylamide,and play a blocking role in the transition site from early apoptosis to late apoptosis.After the intervention of catechins,DNA damage and broken fragments in Hep G2 cells are significantly reduced.In addition,the intervention effect of non-ester catechin EC was better than ester catechin EGCG.Further analysis showed that the protective effect of catechin on the metabolism of acrylamide may be related to the phenolic hydroxyl in the flavanol structure.To explore the changes in the levels of exposure markers in vivo in which acrylamide ACTS on organisms.By long-term gavage of acrylamide in rats,the blood samples obtained were detected by high resolution mass spectrometry to track the metabolism process in vivo.Based on Compound Discovery software and Chem Spider database,differential metabolites were found before and after exposure.Through comparison,it can be found that the intake of acrylamide mainly interferes with the metabolism of phenylalanine in the body,and also affects the energy metabolism pathway of tricarboxylic acid.Then,the existing physical and biochemical model parameters of acrylamide are used to construct the PBTK model based on locus differential equation,and the theoretical model is correlated with the actual value for verification.At the same time,the stability value of the singledose model was deduced,and an association model was constructed to simulate the daily exposure of acrylamide and the stability value level of the biomarker,providing an analytical means for the accurate assessment of the actual human exposure.Finally,turn back to the queue study.We set student population the queue in the college,with a randomized,double-blind controlled experiment,using water-soluble antioxidant of bamboo leaves(AOB-w)and tea polyphenols as drug intervention.We collected the urine of volunteers within 48 hours for toxicokinetics research and blood samples within 10 d for effects of mediumterm exposed to acrylamide,and established the AOB-w and tea polyphenols toxicokinetics kinetic model for intervention.The results showed that both AOB-w and tea polyphenols could reduce the level of urine biomarkers of acrylamide in the form of thiol uric acid metabolites,especially for female subjects.As for the medium term exposure index dominated by hemoglobin adducts,AOB-w accelerated the metabolism of hemoglobin adducts of acrylamide and glycine in the blood of female subjects.Compared with AOB-w group,the G/A ratio decreased significantly at the end of the test,which may have promoted the detoxification pathway from glycidamide to non-toxic 2,3-dihydroxypropiamide.However,there was no significant difference in the results of tea polyphenols intervention.This chapter is of great significance for the risk assessment of acrylamide and the establishment of population exposure risk database,as well as the research idea of natural product intervention.Here we firstly started from the daily exposure level of acrylamide and established the population cohort of the two places by using the epidemiological survey method.Studies on the toxic effects of acrylamide from the multi-factor complex exploration of in vitro cell experiment to the screening of markers of blood metabolism difference at the animal level,we found the key metabolic pathway related to the toxic effects of acrylamide;Second,a randomized double-blind study was conducted to establish the metabolic kinetics analysis of acrylamide exposure in short and medium term.Finally,this research also provided at the cellular level,the crowd dietary intervention level,the flavonoids acrylamide exposure levels have a positive effective intervention,inside and outside for acrylamide exposure associated and biological exposure associated with health effects in practice to explore,for other research provides reference.Also,our study will be beneficial to the study of other food processing pollutants nutritional toxicology.