Nrf2 activation is required for ligustrazine to inhibit hepatic steatosis in alcohol-preferring mice and hepatocytes

Toxicological Sciences

Volumn 155, Issue 2, 2017, Pages 432-443

  Lu, Chunfeng ^a   Xu, Wenxuan ^a   Shao, Jiangjuan ^a   Zhang, Feng ^a   Chen, Anping ^b   Zheng, Shizhong ^a  

^a NANJING UNIVERSITY OF CHINESE MEDICINE   (China)

^b SAINT LOUIS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Alcoholic liver disease; Hepatic steatosis; Hypoxia inducible factor 1 alpha; Ligustrazine; Nuclear factor (erythroid derived 2) like 2

Indexed keywords

AGENTS AFFECTING PROTEIN METABOLISM; ALANINE AMINOTRANSFERASE; ALKALINE PHOSPHATASE; ASPARTATE AMINOTRANSFERASE; BETA ACTIN; CHOLESTEROL; CRYOPYRIN; DIMETHYLOXALYLGLYCINE; GLUTATHIONE CYSTEINE LIGASE MODIFIER SUBUNIT; GLYCERALDEHYDE 3 PHOSPHATE DEHYDROGENASE; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; HYPOXIA INDUCIBLE FACTOR 1ALPHA; I KAPPA B KINASE ALPHA; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; KELCH LIKE ECH ASSOCIATED PROTEIN 1; LACTATE DEHYDROGENASE; LIPID; LOW DENSITY LIPOPROTEIN CHOLESTEROL; MESSENGER RNA; PEPTIDE SYNTHASE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PROTEIN; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE (PHOSPHATE) DEHYDROGENASE (QUINONE); SHORT HAIRPIN RNA; SMALL INTERFERING RNA; STEROL REGULATORY ELEMENT BINDING PROTEIN 1C; TETRAMETHYLPYRAZINE; TRANSCRIPTION FACTOR NRF2; TRIACYLGLYCEROL; TUMOR NECROSIS FACTOR; UNCLASSIFIED DRUG; ALCOHOL; HIF1A PROTEIN, MOUSE; NFE2L2 PROTEIN, MOUSE; PYRAZINE DERIVATIVE;

ALANINE AMINOTRANSFERASE BLOOD LEVEL; ALCOHOLIC FATTY LIVER; ALKALINE PHOSPHATASE BLOOD LEVEL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; CHOLESTEROL BLOOD LEVEL; CONTROLLED STUDY; DISEASE SEVERITY; DRUG EFFICACY; DRUG MECHANISM; ENZYME ACTIVITY; EVIDENCE BASED PRACTICE; GAIN OF FUNCTION MUTATION; GENE EXPRESSION; GENE SILENCING; HEPATITIS; HUMAN; HUMAN CELL; IN VIVO STUDY; LACTATE DEHYDROGENASE BLOOD LEVEL; LIPID STORAGE; LIVER CELL; LIVER INJURY; LIVER PROTECTION; LOSS OF FUNCTION MUTATION; MALE; MOUSE; MUTATIONAL ANALYSIS; NONHUMAN; OXIDATIVE STRESS; PROTEIN EXPRESSION; PROTEIN FUNCTION; SIGNAL TRANSDUCTION; TRANSCRIPTION INITIATION; TRIACYLGLYCEROL BLOOD LEVEL; ANIMAL; CELL CULTURE; DRUG EFFECTS; GENE KNOCKDOWN; GENETICS; INSTITUTE FOR CANCER RESEARCH MOUSE; LIPID METABOLISM; METABOLISM;

ANIMALS; CELLS, CULTURED; ETHANOL; FATTY LIVER, ALCOHOLIC; GENE KNOCKDOWN TECHNIQUES; HEPATOCYTES; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; LIPID METABOLISM; MALE; MICE; MICE, INBRED ICR; NF-E2-RELATED FACTOR 2; PYRAZINES; SIGNAL TRANSDUCTION;

EID: 85021756820     PISSN: 10966080     EISSN: 10960929     Source Type: Journal    
DOI: 10.1093/toxsci/kfw228     Document Type: Article

References (44)

1. Akira, S., Misawa, T., Satoh, T., and Saitoh, T. (2013). Macrophages control innate inflammation. Diabetes Obes. Metab. 15(Suppl 3), 10-18
2. Barve, A., Khan, R., Marsano, L., Ravindra, K. V., and McClain, C. (2008). Treatment of alcoholic liver disease. Ann. Hepatol. 7, 5-15
3. Chen, A., Zhang, L., Xu, J., and Tang, J. (2002). The antioxidant (-)-epigallocatechin-3-gallate inhibits activated hepatic stellate cell growth and suppresses acetaldehyde-induced gene expression. Biochem. J. 368, 695-704
4. Delima, R. D., Chua, A. C., Tirnitz-Parker, J. E., Gan, E. K., Croft, K. D., Graham, R. M., Olynyk, J. K., and Trinder, D. (2012). Disruption of hemochromatosis protein and transferrin receptor 2 causes iron-induced liver injury in mice. Hepatology 56, 585-593
5. Dong, J., and Ma, Q. (2015). Suppression of basal and carbon nanotube-induced oxidative stress, inflammation and fibrosis in mouse lungs by Nrf2. Nanotoxicology 10, 699-709
6. Friedman, S. L. (2003). Liver fibrosis-from bench to bedside. J. Hepatol. 38(Suppl 1), S38-S53
7. Fu, Y., Zheng, S., Lin, J., Ryerse, J., and Chen, A. (2008). Curcumin protects the rat liver from CCl4-caused injury and fibrogenesis by attenuating oxidative stress and suppressing inflammation. Mol. Pharmacol. 73, 399-409
8. Huang, J., Tabbi-Anneni, I., Gunda, V., and Wang, L. (2010). Transcription factor Nrf2 regulates SHP and lipogenic gene expression in hepatic lipid metabolism. Am. J. Physiol. Gastrointest. Liver Physiol. 299, G1211-G1221
9. Huang, Y., Caputo, C. R., Noordmans, G. A., Yazdani, S., Monteiro, L. H., van den Born, J., van Goor, H., Heeringa, P., Korstanje, R., and Hillebrands, J. L. (2014). Identification of novel genes associated with renal tertiary lymphoid organ formation in aging mice. PLoS One 9, e91850
10. Jungermann, K., and Kietzmann, T. (2000). Oxygen: modulator of metabolic zonation and disease of the liver. Hepatology 31, 255-260
11. Keleku-Lukwete, N., Suzuki, M., Otsuki, A., Tsuchida, K., Katayama, S., Hayashi, M., Naganuma, E., Moriguchi, T., Tanabe, O., Engel, J. D., et al. (2015). Amelioration of inflammation and tissue damage in sickle cell model mice by Nrf2 activation. Proc. Natl. Acad. Sci. U. S. A. 112, 12169-12174
12. Kelly, M., Hwang, J. M., and Kubes, P. (2007). Modulating leukocyte recruitment in inflammation. J. Allergy Clin. Immunol. 120, 3-10
13. Kumar, H., Kim, I. S., More, S. V., Kim, B. W., and Choi, D. K. (2014). Natural product-derived pharmacological modulators of Nrf2/ARE pathway for chronic diseases. Nat. Prod. Rep. 31, 109-139
14. Li, J., French, B., Wu, Y., Vanketesh, R., Montgomery, R., Bardag-Gorce, F., Kitto, J., and French, S. W. (2004). Liver hypoxia and lack of recovery after reperfusion at high blood alcohol levels in the intragastric feeding model of alcohol liver disease. Exp Mol Pathol 77, 184-192
15. Li, J. P., Gao, Y., Chu, S. F., Zhang, Z., Xia, C. Y., Mou, Z., Song, X. Y., He, W. B., Guo, X. F., and Chen, N. H. (2014). Nrf2 pathway activation contributes to anti-fibrosis effects of ginsenoside Rg1 in a rat model of alcohol-and CCl4-induced hepatic fibrosis. Acta Pharmacol. Sin. 35, 1031-1044
16. Li, L., Chen, S. H., Zhang, Y., Yu, C. H., Li, S. D., and Li, Y. M. (2006). Is the hypoxia-inducible factor-1 alpha mRNA expression activated by ethanol-induced injury, the mechanism underlying alcoholic liver disease? Hepatobiliary Pancreat. Dis. Int. 5, 560-563
17. Li, W., Khor, T. O., Xu, C., Shen, G., Jeong, W. S., Yu, S., and Kong, A. N. (2008). Activation of Nrf2-antioxidant signaling attenuates NFkappaB-inflammatory response and elicits apoptosis. Biochem. Pharmacol. 76, 1485-1489
18. Lieber, C. S. (2004). Alcoholic fatty liver: its pathogenesis and mechanism of progression to inflammation and fibrosis. Alcohol 34, 9-19
19. Liu, Z., Wang, J., Huang, X., Li, Z., and Liu, P. (2016). Deletion of sirtuin 6 accelerates endothelial dysfunction and atherosclerosis in apolipoprotein E-deficient mice. Transl. Res. 172, 18-29.e2
20. Lu, C., Jiang, Y., Zhang, F., Shao, J., Wu, L., Wu, X., Lian, N., Chen, L., Jin, H., Chen, Q., et al. (2015). Tetramethylpyrazine prevents ethanol-induced hepatocyte injury via activation of nuclear factor erythroid 2-related factor 2. Life Sci. 141, 119-127
21. Lu, C., Xu, W., Zhang, F., Jin, H., Chen, Q., Chen, L., Shao, J., Wu, L., Lu, Y., and Zheng, S. (2015). Ligustrazine prevents alcohol-induced liver injury by attenuating hepatic steatosis and oxidative stress. Int. Immunopharmacol. 29, 613-621
22. Ludtmann, M. H., Angelova, P. R., Zhang, Y., Abramov, A. Y., and Dinkova-Kostova, A. T. (2014). Nrf2 affects the efficiency of mitochondrial fatty acid oxidation. Biochem J. 457, 415-424
23. Ma, Q., Kinneer, K., Ye, J., and Chen, B. J. (2003). Inhibition of nuclear factor kappaB by phenolic antioxidants: interplay between antioxidant signaling and inflammatory cytokine expression. Mol. Pharmacol. 64, 211-219
24. Nath, B., Levin, I., Csak, T., Petrasek, J., Mueller, C., Kodys, K., Catalano, D., Mandrekar, P., and Szabo, G. (2011). Hepatocytespecific hypoxia-inducible factor-1alpha is a determinant of lipid accumulation and liver injury in alcohol-induced steatosis in mice. Hepatology 53, 1526-1537
25. O'Shea, R. S., Dasarathy, S., and McCullough, A. J. (2010). Alcoholic liver disease. Hepatology 51, 307-328
26. Page, A., Paoli, P. P., Hill, S. J., Howarth, R., Wu, R., Kweon, S. M., French, J., White, S., Tsukamoto, H., Mann, D. A., et al. (2015). Alcohol directly stimulates epigenetic modifications in hepatic stellate cells. J. Hepatol. 62, 388-397
27. Pari, L., and Karthikesan, K. (2007). Protective role of caffeic acid against alcohol-induced biochemical changes in rats. Fundam. Clin. Pharmacol. 21, 355-361
28. Reddy, J. K., and Rao, M. S. (2006). Lipid metabolism and liver inflammation. II. Fatty liver disease and fatty acid oxidation. Am. J. Physiol. Gastrointest. Liver Physiol. 290, G852-G858
29. Schwartz, J. M., and Reinus, J. F. (2012). Prevalence and natural history of alcoholic liver disease. Clin. Liver Dis. 16, 659-666
30. Sozio, M. S., Liangpunsakul, S., and Crabb, D. (2010). The role of lipid metabolism in the pathogenesis of alcoholic and nonalcoholic hepatic steatosis. Semin. Liver Dis. 30, 378-390
31. Stewart, S., Jones, D., and Day, C. P. (2001). Alcoholic liver disease: new insights into mechanisms and preventative strategies. Trends Mol. Med. 7, 408-413
32. Sun, G., Li, Y., and Ji, Z. (2015). Atorvastatin attenuates inflammation and oxidative stress induced by ischemia/reperfusion in rat heart via the Nrf2 transcription factor. Int. J. Clin. Exp. Med.8, 14837-14845
33. Svegliati-Baroni, G., Inagaki, Y., Rincon-Sanchez, A. R., Else, C., Saccomanno, S., Benedetti, A., Ramirez, F., and Rojkind, M. (2005). Early response of alpha2(I) collagen to acetaldehyde in human hepatic stellate cells is TGF-beta independent. Hepatology 42, 343-352
34. Svegliati-Baroni, G., Ridolfi, F., Di Sario, A., Saccomanno, S., Bendia, E., Benedetti, A., and Greenwel, P. (2001). Intracellular signaling pathways involved in acetaldehyde-induced collagen and fibronectin gene expression in human hepatic stellate cells. Hepatology 33, 1130-1140
35. Tomita, K., Teratani, T., Suzuki, T., Shimizu, M., Sato, H., Narimatsu, K., Usui, S., Furuhashi, H., Kimura, A., Nishiyama, K., et al. (2014). Acyl-CoA:cholesterol acyltransferase 1 mediates liver fibrosis by regulating free cholesterol accumulation in hepatic stellate cells. J. Hepatol. 61, 98-106
36. Wang, B. B., Cheng, J. Y., Gao, H. H., Zhang, Y., Chen, Z. N., and Bian, H. (2010). Hepatic stellate cells in inflammationfibrosis-carcinoma axis. Anat. Rec. (Hoboken) 293, 1492-1496
37. Wu, K. C., Liu, J., and Klaassen, C. D. (2012). Role of Nrf2 in preventing ethanol-induced oxidative stress and lipid accumulation. Toxicol. Appl. Pharmacol. 262, 321-329
38. Wu, X., Zhang, F., Xiong, X., Lu, C., Lian, N., Lu, Y., and Zheng, S. (2015). Tetramethylpyrazine reduces inflammation in liver fibrosis and inhibits inflammatory cytokine expression in hepatic stellate cells by modulating NLRP3 inflammasome pathway. IUBMB Life 67, 312-321
39. Yuasa, C., Miyoshi, O., Fukui, K., and Oka, T. (2000). Hyperlipemia and early pancreatic injury induced by ethanol intake in rats. J. Nutr. Sci. Vitaminol. (Tokyo) 46, 297-301
40. Zeng, T., Zhang, C. L., Song, F. Y., Zhao, X. L., and Xie, K. Q. (2012). Garlic oil alleviated ethanol-induced fat accumulation via modulation of SREBP-1, PPAR-alpha, and CYP2E1. Food Chem. Toxicol. 50, 485-491
41. Zhai, X., Yan, K., Fan, J., Niu, M., Zhou, Q., Zhou, Y., and Chen, H. (2013). The beta-catenin pathway contributes to the effects of leptin on SREBP-1c expression in rat hepatic stellate cells and liver fibrosis. Br. J. Pharmacol. 169, 197-212
42. Zhang, F., Zhang, Z., Chen, L., Kong, D., Zhang, X., Lu, C., Lu, Y., and Zheng, S. (2014). Curcumin attenuates angiogenesis in liver fibrosis and inhibits angiogenic properties of hepatic stellate cells. J. Cell Mol. Med. 18, 1392-1406
43. Zhang, W., Niu, M., Yan, K., Zhai, X., Zhou, Q., Zhang, L., and Zhou, Y. (2013). Stat3 pathway correlates with the roles of leptin in mouse liver fibrosis and sterol regulatory element binding protein-1c expression of rat hepatic stellate cells. Int. J. Biochem. Cell Biol. 45, 736-744
44. Zhou, J., Febbraio, M., Wada, T., Zhai, Y., Kuruba, R., He, J., Lee, J. H., Khadem, S., Ren, S., Li, S., et al. (2008). Hepatic fatty acid transporter Cd36 is a common target of LXR, PXR, and PPARgamma in promoting steatosis. Gastroenterology 134, 556-567