RESEARCHPAPER

Protective Effects of Ethoxyquin on Lipopolysaccharide and D-Galactosamine Induced Acute Liver Injury of Mice

  • LI Peixuan ,
  • WU Zhikai ,
  • SUN Youpeng ,
  • FU Yiwu ,
  • WANG Xia ,
  • WANG Jingjing ,
  • ZHOU Ershun ,
  • YANG Zhengtao
Expand
  • College of Life Sciences and Engineering, Foshan University, Foshan 528225, China

Received date: 2022-01-08

  Online published: 2022-06-14

Abstract

This experiment used lipopolysaccharide (LPS) and D-galactosamine (D-GalN) to establish a mouse model of acute liver injury, to illustrate the antioxidant effect and mechanism of ethoxyquin in vivo. Forty Kunming mice were randomly divided into the following 5 groups:control group, model group and ethoxyquin low (50 μg/kg), medium (100 μg/kg) and high dose (200 μg/kg) groups, each group contained 8 mice. Each ethoxyquin dose group was given by continuous intraperitoneal injection for 3 days, and the control group and model group were treated with normal saline in the same way. After 1 h of administration on the 3rd day, except for the control group, the mice in other groups were intraperitoneally injected with LPS (500 μg/kg) and D-GalN (500 mg/kg). After 4 h, the blood of mice of each group was collected, and the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were detected. The liver tissue samples were collected, then observed the pathological changes of liver tissues. The glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), myeloperoxidase (MPO) activities and malondialdehyde (MDA) content in liver were determined. The quantitative reverse transcription PCR was used to detect the mRNA relative expression level of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) in liver, and Western Blot was used to detect the related protein expression of nuclear factor-kappa B (NF-κB) and nuclear factor erythroid-2 related factor 2 (Nrf2) signaling pathways in liver. The result showed that compared with the model group, the serum ALT and AST activities of ethoxyquin low, medium and high dose groups were significantly decreased (P<0.05), the pathological damage of liver tissue was alleviated, the MDA content and MPO activity in liver were significantly decreased (P<0.05), the liver GSH-Px activity was significantly increased (P<0.05), the mRNA relative expression levels of TNF-α, IL-1β and IL-6 were significantly down-regulated (P<0.05), the phosphorylation level of p65 protein in liver was significantly decreased (P<0.05), and the Nrf2 and heme oxygenase-1 (HO-1) protein expression levels were significantly increased (P<0.05). In conclusion, ethoxyquin may exhibit a protective effect on liver by inhibiting the NF-κB signaling pathway and activating the Nrf2 signaling pathway to attenuate the oxidative stress and inflammation caused by LPS and D-GalN in mice.

Cite this article

LI Peixuan , WU Zhikai , SUN Youpeng , FU Yiwu , WANG Xia , WANG Jingjing , ZHOU Ershun , YANG Zhengtao . Protective Effects of Ethoxyquin on Lipopolysaccharide and D-Galactosamine Induced Acute Liver Injury of Mice[J]. Chinese Journal of Animal Nutrition, 2022 , 34(6) : 4032 -4040 . DOI: 10.3969/j.issn.1006-267x.2022.06.062

References

[1] MEREL S, REGUEIRO J, BERNTSSEN M H G, et al.Identification of ethoxyquin and its transformation products in salmon after controlled dietary exposure via fish feed[J].Food Chemistry, 2019, 289:259-268.
[2] 梁先伟, 沈家鲲, 黄羽盛, 等.饲料加工工艺和抗氧化剂添加对蛋雏鸡生长性能及抗氧化指标的影响[J].中国家禽, 2017, 39(14):65-67. LIANG X W, SHEN J K, HUANG Y S, et al.Effects of feed processing technology and antioxidant addition on growth performance and antioxidant indexes of laying chicks[J].China Poultry, 2017, 39(14):65-67.(in Chinese)
[3] 刘东鑫, 余功富, 金洁瑜, 等.合成抗氧化剂对断奶犊牛抗氧化干预的研究进展[J].中国畜牧杂志, 2018, 54(9):5-9. LIU D X, YU G F, JIN J Y, et al.Allieviation of oxidative stress of early weaned calves by synthetic antioxidant:a review[J].Chinese Journal of Animal Science, 2018, 54(9):5-9.(in Chinese)
[4] EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP).Safety and efficacy of ethoxyquin (6-ethoxy-1, 2-dihydro-2, 2, 4-trimethylquinoline) for all animal species[J].EFSA Journal, 2015, 13(11):4272.
[5] 韩超.丹参多糖对小鼠免疫性肝损伤的炎症调节机制研究[D].硕士学位论文.保定:河北农业大学, 2018. HAN C.Study on inflammatory regulatory mechanism of Salvia miltiorrhiza polysaccharides on mice immunological liver injury[D].Master's Thesis.Baoding:Hebei Agricultural University, 2018.(in Chinese)
[6] LV H M, YANG H H, WANG Z F, et al.Nrf2 signaling and autophagy are complementary in protecting lipopolysaccharide/D-galactosamine-induced acute liver injury by licochalcone A[J].Cell Death & Disease, 2019, 10(4):313.
[7] TIAN Q, WANG G J, ZHANG Y M, et al.Engeletin inhibits lipopolysaccharide/D-galactosamine-induced liver injury in mice through activating PPAR-γ[J].Journal of Pharmacological Sciences, 2019, 140(3):218-222.  
[8] MURIEL P, RAMOS-TOVAR E, MONTES-PÁEZ G, et al.Chapter 40-experimental models of liver damage mediated by oxidative stress[M]//MURIEL P.Liver pathophysiology:therapies and antioxidants.London:Academic Press, 2017:529-546.
[9] ELLIS E M, JUDAH D J, NEAL G E, et al.An ethoxyquin-inducible aldehyde reductase from rat liver that metabolizes aflatoxin B1 defines a subfamily of aldo-keto reductases[J].Proceedings of the National Academy of Sciences of the United States of America, 1993, 90(21):10350-10354.  
[10] 王珺.乙氧基喹啉、氧化鱼油和烟酸铬对大黄鱼与鲈鱼生长性能的影响及其(或代谢物)在鱼体组织中残留的研究[D].博士学位论文.青岛:中国海洋大学, 2010. WANG J.Effects of ethoxyquin, oxidized fish oil and chromium polynicotinate on the growth performance and their (or metabolites) residues in tissues of large yellow croaker Pseudosciaena crocea and Japanese seabass Lateolabrax japonicus[D].Ph.D.Thesis.Qingdao:Ocean University of China, 2010.(in Chinese)
[11] OHSHIMA M, LAYUG D V, YOKOTA H O, et al.Effect of graded levels of ethoxyquin in alfalfa leaf extracts on carotenoid and cholesterol concentrations in chicks[J].Animal Feed Science and Technology, 1996, 62(2/3/4):141-150.
[12] ZHU Y H, CHEN X B, RAO X L, et al.Saikosaponin a ameliorates lipopolysaccharide and D-galactosamine-induced liver injury via activating LXRα[J].International Immunopharmacology, 2019, 72:131-137.
[13] LIU Y Y, LI F, ZHANG L, et al.Taurine alleviates lipopolysaccharide-induced liver injury by anti-inflammation and antioxidants in rats[J].Molecular Medicine Reports, 2017, 16(5):6512-6517.  
[14] KHEDR S I, MOKHAMER E H M, HASSAN A A A, et al.Psidium guajava Linn leaf ethanolic extract:in vivo giardicidal potential with ultrastructural damage, anti-inflammatory and antioxidant effects[J].Saudi Journal of Biological Sciences, 2021, 28(1):427-439.  
[15] CHEN X, CAO J H, SUN Y, et al.Ethanol extract of Schisandrae chinensis fructus ameliorates the extent of experimentally induced atherosclerosis in rats by increasing antioxidant capacity and improving endothelial dysfunction[J].Pharmaceutical Biology, 2018, 56(1):612-619.  
[16] KIM Y, ALLEN E, BAIRD L A, et al.NF-κB RelA is required for hepatoprotection during pneumonia and sepsis[J].Infection and Immunity, 2019, 87(8):e00132-19.
[17] LE NA N T, DUC LOC S, MINH TRI N L, et al.Nanomelanin potentially protects the spleen from radiotherapy-associated damage and enhances immunoactivity in tumor-bearing mice[J].Materials, 2019, 12(10):1725.
[18] KONG D J, FU P, ZHANG Q, et al.Protective effects of Asiatic acid against pelvic inflammatory disease in rats[J].Experimental and Therapeutic Medicine, 2019, 17(6):4687-4692.
[19] ZHANG L, PENG H, ZHANG W, et al.Yeast cell wall particle mediated nanotube-RNA delivery system loaded with miR365 antagomir for post-traumatic osteoarthritis therapy via oral route[J].Theranostics, 2020, 10(19):8479-8493.  
[20] JO A, YOO H J, LEE M.Robustaflavone isolated from Nandina domestica using bioactivity-guided fractionation downregulates inflammatory mediators[J].Molecules, 2019, 24(9):1789.
[21] XU Q M, XU J, ZHANG K F, et al.Study on the protective effect and mechanism of Dicliptera chinensis (L.) Juss (Acanthaceae) polysaccharide on immune liver injury induced by LPS[J].Biomedicine & Pharmacotherapy, 2021, 134:111159.
[22] HAN X D, ZHANG Y Y, WANG K L, et al.The involvement of Nrf2 in the protective effects of (-)-epigallocatechin-3-gallate (EGCG) on NaAsO2-induced hepatotoxicity[J].Oncotarget, 2017, 8(39):65302-65312.  
[23] YAO H, SUN J Y, WEI J, et al.Kaempferol protects blood vessels from damage induced by oxidative stress and inflammation in association with the Nrf2/HO-1 signaling pathway[J].Frontiers in Pharmacology, 2020, 11:1118.
[24] PARK E J, DUSABIMANA T, JE J, et al.Honokiol protects the kidney from renal ischemia and reperfusion injury by upregulating the glutathione biosynthetic enzymes[J].Biomedicines, 2020, 8(9):352.
[25] MALIK S A, KHOLE S, MITTAL S P K, et al.Differential response of antioxidant defense in HepG2 cells on exposure of Livotrit®, in a concentration dependent manner[J].Journal of Traditional and Complementary Medicine, 2019, 9(1):38-44.  
Outlines

/