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Toxic Effects And Mechanisms Of Quinoline Induced Oxidative Stress In Mouse Hepatocytes

Posted on:2024-05-11Degree:MasterType:Thesis
Country:ChinaCandidate:Y Z LiFull Text:PDF
GTID:2531306920982059Subject:Resources and environment
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Quinoline is one of the typical representatives of nitrogen heterocyclic compounds.In addition to natural sources,more of it comes from artificial synthesis,mainly in coking wastewater,Coal gasification wastewater and wood phenol oil,and also in tobacco smoke.Quinoline is an important fundamental structure in drug development,so there are more and more methods for synthesizing quinoline and its derivatives.In addition,quinoline is a raw material for paints,dyes,and other related chemicals,and its derivatives can be used as fungicides,corrosion inhibitors,etc.Therefore,it has also been detected in wastewater from related industries.Due to its high water solubility and high diffusion,it also has a high detection concentration in the environment.In individual studies,the liver,as the target organ of quinoline action,has 4 times the mutation frequency higher than the control group,while no significant effects were found in other organs such as the lungs,kidneys,or spleen.As an important detoxification and metabolic organ,hepatocytes contain a large number of mitochondria in order to maintain the normal progress of life activities such as energy and electron transmission.Relevant research shows that quinoline can destroy the inner and outer membranes of mitochondria,which will destroy the original redox balance and induce oxidative stress in cells.But currently there is a lack of research in this area.Therefore,in this paper,mouse hepatocytes and antioxidant enzymes are selected as research objects to study the oxidative stress effect and mechanism of quinoline on hepatocytes at cellular and molecular levels.The research content mainly includes the following four parts:In the first chapter,the properties and sources of heterocyclic compounds and their similarities and differences with polycyclic aromatic hydrocarbons are discussed.This article introduces the uses and research progress of the nitrogen heterocyclic compound quinoline and its derivatives,summarizes the current pollution status and toxicity research of quinoline,proposes urgent scientific problems in the research field,and introduces the research purpose,content,and significance of this study.In Chapter 2,the primary hepatocytes of mice were selected as the research object.After exposure to different concentrations of quinoline,the oxidative damage and mechanism of quinoline on hepatocytes were clarified by using the oxidative stress effect.After exposed to quinoline,the activity of hepatocytes decreased.When the concentration of exposed quinoline further increases,the activity of hepatocytes decreased significantly,indicating the hepatotoxicity of quinoline.The intracellular ROS level did not change significantly at lower concentrations.When the quinoline exposure concentration reached 25 mg/L,the intracellular ROS level gradually increased.In the study of antioxidant enzymes and antioxidant substances related to oxidation-reduction balance,it was found that quinoline had little effect on SOD enzyme,but it has a huge impact on CAT enzyme.Antioxidants such as GSH may remove some H2O2 and reduce the ROS level in cells.However,with the increase of exposure concentration of quinoline,antioxidant substances cannot remove too much ROS,and the total antioxidant capacity of cells decreases.The unsaturated fatty acids on the cell membrane were oxidized,the content of MDA increased,the membrane permeability increased,and the LDH enzyme flowed out.Moreover,quinoline can induce the decrease of mitochondrial membrane potential,resulting in mitochondrial damage,and then inducing apoptosis.At the molecular level,quinoline can cause DNA damage and ROS being one of the culprits.At the molecular level,this study confirms that quinoline can bind to DNA through intercalation,making the DNA double helix more compact.The binding of quinoline to DNA may depend on adenine B18 and guanine B16In chapter 3,the dose effect of quinoline was investigated at the molecular level with SOD and CAT as the research objects.The results showed that quinoline could change the particle size and secondary structure of the system and loosen the protein structure by combining CAT with hydrophobic interaction.This also changes the microenvironment around the chromophore and reduces the polarity of the environment around the chromophore,leading to fluorescence sensitization.The results of molecular docking showed that quinoline affected Tyr 357,which was related to CAT activity,resulting in changes in CAT enzyme activity and synchronous fluorescence.During the binding process of quinoline and SOD,the protein structure also changed.Cu ion directly interacts with superoxide anion radical,while Zn ion plays a role in the environment around the stable active center.Because the binding site is far from the active center of SOD,it has little effect on the activity of SOD.The fourth chapter summarizes the main work of this paper,summarizes the innovation points,and puts forward the shortcomings and research prospects of this paper.At the cellular and molecular levels,this study evaluated the oxidative stress-related toxicity mechanism of quinoline induced by different doses of quinoline in hepatocytes,revealed the main pathway of quinoline affecting the antioxidant system by simulating the combination model of quinoline and antioxidant protein,and provided scientific basis and methodological reference for the study of the mechanism of quinoline causing hepatotoxicity at the cellular and molecular levels.
Keywords/Search Tags:quinoline, mouse hepatocytes, oxidative stress, catalase
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