Dissertation > Excellent graduate degree dissertation topics show

Effect of Quercetin/hemeoxygenase-1/bilirubin System on Ethanol-induced Injury of Rat Hepatocytes

Author: JieQinFeng
Tutor: YaoPing；LiuLieGang
School: Huazhong University of Science and Technology
Course: Nutrition and Food Hygiene
Keywords: Ethanol Quercetin HO-1 Bilirubin Oxidative damage Inflammatory stress
CLC: R285.5
Type: Master's thesis
Year: 2011
Downloads: 23
Quote: 0
Read: Download Dissertation

Abstract


Background: With the improvement of people's living standards and lifestyle changes, the incidence of alcoholic liver disease (alcoholic liver disease, ALD) was gradually increased the potential to become the second largest category of liver disease after viral hepatitis, the prevention and treatment is an important public health problem worldwide. ALD pathogenesis is more complex, which concern oxidative damage and inflammatory stress doctrine. Recently, an increasing number of studies found that quercetin as a food source for a wide range of flavonoids, antioxidant, anti-inflammatory, anti-apoptotic biological effects, also has a significant protective effect of ALD. Further studies have shown that the protective effect of quercetin on ALD its by induced liver type I heme oxygenase (heme oxygenase-1, HO-1), further amplifying its antioxidant activity. However, as one of the metabolites of the HO-1 catalytic heme exploded bilirubin, has long been considered to be body of toxic metabolites. Only in recent years, with in-depth research, scholars discovered normal physiological concentration of bilirubin has a good anti-oxidation, anti-inflammatory, anti-apoptotic biological activity. Bilirubin whether to participate or mediated protective effect of HO-1 on hepatocytes in alcoholic injury, No directly related to the research reported. Therefore, due to oxidative damage of liver cells and inflammatory stress protective effect of HO-1 metabolite bilirubin to alcohol, not only to further improve the quercetin / HO-1 antagonistic mechanism of alcoholic liver injury, but also may be better to expand the awareness of the people of bilirubin. Objective: 1. Explore quercetin-induced HO-1 bilirubin generated potential protective effect on liver cells from oxidative damage induced by ethanol and its dose-effect relationship, and to explore the bilirubin cells of ethanol-induced oxidative stress triggered The apoptotic whether antagonistic effect; 2. analysis of bilirubin in the liver cells from oxidative and inflammatory dual stress the potential protective effect. Methods: (1) two-step collagenase perfusion digestion were isolated and cultured primary rat hepatocytes induced oxidative damage of hepatic cells, and at the same time give the anhydrous ethanol (200 mmol / L, 24h) alone or in combination give quercetin (100μmol / L), Hemin has (heme, HO-1 inducer, 20μmol / L), zinc protoporphyrin-IX (ZnPP-IX, HO-1 inhibitor, 10μmol / L) and different doses of exogenous bilirubin (2,10,25,100 μmol / L), the cells were observed AST, LDH enzyme leakage, SOD activity, GSH levels and lipid oxidation products MDA and ROS generation and direct bilirubin levels of endogenous and detection mitochondrial membrane potential, the apoptosis rate changes. (200 mmol / L), while in primary rat hepatocytes after ethanol incubation of inflammatory cytokines (TNF-α lt; Addition of exogenous 5 ng / ml gt; IL-6 lt; 2 ng / ml gt ;) induced cellular oxidative and inflammatory dual stress added bilirubin intervention, observation of the oxidative stress related indicators change, analysis of bilirubin superimposed inflammatory stress on the liver cells alcoholic oxidative damage based on the protection of role. Results: 1. Quercetin on ethanol-induced liver cell AST and LDH enzyme leakage, Depletion of cellular GSH and SOD, MDA and ROS generation are significantly inhibited, and improve the level of endogenous bilirubin ; the heme performance effects of quercetin similar; HO-1 inhibitor ZnPP-IX is significantly inhibited the protective effect of quercetin. In doses of exogenous bilirubin (25μmol / L, 10μmol / L) of ethanol-induced liver cell AST and LDH enzyme leakage consumption of GSH and SOD and MDA and ROS generation also significantly inhibited no significant protective effect of low doses of bilirubin (2μmol / L), high doses of bilirubin (100μmol / L) not only showed some cytotoxicity, and increased the cytotoxicity of ethanol. Quercetin effectively antagonize ethanol-induced mitochondrial membrane potential decline and reduce the rate of apoptosis, heme showed a similar effect with quercetin and ZnPP-IX quercetin significantly inhibited the protective effect. Cells incubated ethanol to exogenous bilirubin (25 μmol / L), is also effective to maintain the level of mitochondrial membrane potential and reduce the rate of apoptosis. 4. Exogenous inflammatory cytokines and ethanol co-treatment liver cells, increased AST and LDH enzyme leakage induced by ethanol consumption of GSH and SOD and MDA and ROS generation. Oxidation inflammatory dual stress, exogenous bilirubin (25μmol / L) significantly inhibited the changes in cellular oxidative stress indicators. Conclusion: quercetin induced HO-1 can inhibit liver cells alcoholic oxidative damage and inflammatory stress, and can effectively antagonize alcohol-induced mitochondrial membrane potential and apoptosis. Further, as HO-1 in catalytic metabolite, bilirubin, there may be mediated by the HO-1 in the protective effect.

Related Dissertations

  1. Preliminary Study of Phosphorylation Effect on UGT1A3 Metabolism Activity Towards Drugs,R346
  2. The Study of Lead Exposure on Cyprinus Carpio Ovary Epithelial Cells,X174
  3. Some Fluorescence Quenching Spectral Analysis Interacted with Bio-related Molecules,X832
  4. Studies on Prediction Models for Fruit Decay and Shelf-Life of Postharvest Strawberry,TS255.4
  5. Studies on Prediction Models for Fruit Decay and Shelf-Life of Postharvest Chinese Bayberry,S667.6
  6. Cross-Talk between Ethylene and Heme-Heme Oxygenase Signal System in Primary Root Growth Inhibition of Etiolated Tomato Seedlings,S641.2
  7. Physical Modification of the Soybean Protein Concentrate by Alcohol Extraction,TS201.21
  8. Effects of Quercetin on Human Bladder Cancer Cells (EJ) and STAT3 Signaling Pathway,R737.14
  9. Taxifolin , quercetin on LPS-induced abortion mouse macrophages affect the uterus,R285.5
  10. PtRh / Pt 5 / C Catalyst Preparation, Characterization and Electrocatalytic Oxidation of Ethanol,TM911.4
  11. Construction of an integrated large-scale feed mills with an annual output of 170,000 tons integrated feed mill design and construction,S816
  12. The Experimental Study of Radiofrequency Ablation Combined with Percutaneous Ethanol Injection in Vivo Rabbit Liver,R817.5
  13. Study on Mechanisms of Testis Oxidative Injury and Apoptosis in Freshwater Crab (Sinopotamon henanense) Induced by Cadmium,X174
  14. Study on the Kinetics of Acetic Acid Hydrogenation to Ethanol,TQ223.122
  15. Influence of Baicalin on the Heart and Kidney Injury Induced by Iron Overload,R285
  16. Effect of Ammonium Perchlorate on Iodine Uptake and Antioxidant Capacity of Thyroid,R114
  17. Study on the Different Expression of Heme Oxygenase Enzyme in Human Testis of Fertile and Infertile Males,R698.2
  18. Complex biological agents on Culex Culex pipiens pallens Coquillett 4 instar larvae of toxic effects,R184
  19. Copper and chromium on the mechanism of toxicity and chlorella detoxification method,X173
  20. Two ethanol monoisopropanolamine Synthesis of,TQ226.31

CLC: > Medicine, health > Chinese Medicine > Of Pharmacy > Pharmacology > Chinese medicine Experimental Pharmacology
© 2012 www.DissertationTopic.Net  Mobile