EXPERIMENTAL METHOD AND ANIMAL

Effects of Microbe-Derived Antioxidants on Oxidative Damage and Inflammatory Response in Liver of Mice Induced by Dextran Sulfate Sodium Salt

  • LI Li ,
  • MA Sheng ,
  • ZHANG Jing ,
  • XU Weina ,
  • XU Jianxiong
Expand
  • Shanghai Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiaotong University, Shanghai 200240, China

Received date: 2020-12-16

  Online published: 2021-07-06

Supported by

 

Abstract

This experiment was conducted to explore the dextran sulfate sodium salt (DSS) induced liver damage of mice and the relieving effects and possible mechanism of microbe-derived antioxidants (MA). Forty-eight 6-week-old C57BL/6J male mice were randomly divided into 4 groups with 12 mice in each group after 1 week of pre feeding. Each mouse in the control group and DSS group was given normal saline 0.020 mL/g BW by gavage every day, each mouse in the low-dose MA group (LMA group) was given 0.002 mL/g BW MA by gavage every day, and each mouse in the high-dose MA group (HMA group) group was given 0.003 mL/g BW MA by gavage every day. Mice in the control group drank double distilled water every day; mice in other groups drank double distilled water from 1 to 7 days, and drank double distilled water contained 3% DSS from 8 to 14 days. The experiment lasted for 14 days. 1) compared with the control group, the DSS group showed inflammatory cell infiltration and steatosis in the central venous duct area of liver tissue; the contents of hydrogen peroxide (H2O2) and malondialdehyde (MDA) in liver were significantly increased (P<0.01), the total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px) activities and glutathione (GSH) content and total antioxidant capacity (T-AOC) in liver were significantly decreased (P<0.05 or P<0.01), and the liver mitochondrial membrane potential was significantly decreased (P<0.05). Compared with the DSS group, the DSS, MA treatment improved the inflammatory cell infiltration and steatosis in the central venous duct area of liver tissue; the liver H2O2 content of LMA group was significantly decreased (P<0.05), and the liver T-AOC and GSH-Px activity were significantly increased (P<0.05); the contents of H2O2 and MDA in liver of HMA group were significantly decreased (P<0.01), and the T-SOD, GSH-Px activities and GSH content and T-AOC in liver were significantly increased (P<0.05); the liver mitochondrial membrane potential of LMA group and HMA group was significantly increased (P<0.05). 2) Compared with the control group, the mRNA relative expression levels of apoptosis-associated speck-like protein containing a CARD (ASC), cysteine aspartatespecific proteinase-1 (Caspase-1), interleukin-1β (IL-1β), extracellular regulated protein kinases (PERK), activating transcription factor 6 (ATF6), inositol requiring enzyme 1 (IRE1), glucose regulated protein 78 (GRP78) and telomerase reverse transcriptase (Tert) in liver of DSS group were significantly increased (P<0.05). Compared with the DSS group, the mRNA relative expression levels of ASC, Caspase-1, IL-1β and GRP78 in liver of HMA group were significantly decreased (P<0.05). In conclusion, DSS induces oxidative stress, injury and inflammation in liver of mice, MA have a significant alleviating effect on this, the alleviating effect of high-dose MA is stronger, and the Nod-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome is involved in regulating inflammation.

Cite this article

LI Li , MA Sheng , ZHANG Jing , XU Weina , XU Jianxiong . Effects of Microbe-Derived Antioxidants on Oxidative Damage and Inflammatory Response in Liver of Mice Induced by Dextran Sulfate Sodium Salt[J]. Chinese Journal of Animal Nutrition, 2021 , 33(7) : 4123 -4132 . DOI: 10.3969/j.issn.1006-267x.2021.07.053

References

[1] UKO V,THANGADA S,RADHAKRISHNAN K.Liver disorders in inflammatory bowel disease[J].Gastroenterology Research and Practice,2012,2012:642923.
[2] ROGLER G.Gastrointestinal and liver adverse effects of drugs used for treating IBD[J].Best Practice & Research Clinical Gastroenterology,2010,24(2):157-165.  
[3] CHOI J H,MOON C M,SHIN T S,et al.Lactobacillus paracasei-derived extracellular vesicles attenuate the intestinal inflammatory response by augmenting the endoplasmic reticulum stress pathway[J].Experimental & Molecular Medicine,2020,52(12):423-437.
[4] KITAJIMA S,TAKUMA S,MORIMOTO M.Tissue distribution of dextran sulfate sodium (DSS) in the acute phase of murine DSS-induced colitis[J].Journal of Veterinary Medical Science,1999,61(1):67-70.  
[5] LI B,ALLI R,VOGEL P,et al.IL-10 modulates DSS-induced colitis through a macrophage-ROS-NO axis[J].Mucosal Immunology,2014,7(4):869-878.  
[6] RIGHI N C,SCHUCH F B,DE NARDI A T,et al.Effects of vitamin C on oxidative stress,inflammation,muscle soreness,and strength following acute exercise:meta-analyses of randomized clinical trials[J].European Journal of Nutrition,2020,59(7):2827-2839.  
[7] PIRHADI-TAVANDASHTI N,IMANI H,EBRAHIMPOUR-KOUJAN S,et al.The effect of vitamin E supplementation on biomarkers of endothelial function and inflammation among hemodialysis patients:a double-blinded randomized clinical trial[J].Complementary Therapies in Medicine,2020,49:102357.
[8] CHEN X D,SHO T K M,XU W N,et al.Microbe-derived antioxidants promote the expression of nutrient transporters through regulating apoptosis and autophagy in mice challenged with diquat[J].International Journal of Agriculture And Biology,2019,22(5):1155-1160.
[9] 徐雪,TAKAMI S,张京,等.微生物源性抗氧化剂对diquat诱导的小鼠肝脏氧化应激、内质网应激和功能的影响[J].中华肝脏病杂志,2020,28(5):441-445. XU X,TAKAMI S,ZHANG J,et al.Effects of microbial-derived antioxidants on diquat-induced oxidative stress,endoplasmic reticulum stress and function in mice liver[J].Chinese Journal of Hepatology,2020,28(5):441-445.(in Chinese)
[10] SAKAMURU S,ATTENE-RAMOS,XIA M H.Mitochondrial membrane potential assay[M]//ZHU H,XIA M.High-throughput screening assays in toxicology.New York,NY:Humana Press,2016.
[11] SHIMIZU S,NARITA M,TSUJIMOTO Y.Correction:Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC[J].Nature,2000,399(6735):483-487.
[12] GIANNINI E,BOTTA F,FASOLI A,et al.Progressive liver functional impairment is associated with an increase in AST/ALT ratio[J].Digestive Diseases and Sciences,1999,44(6):1249-1253.  
[13] 苗启翔,谢彦娇,唐湘方,等.氧化应激的产生及其对畜禽肝脏功能的影响与机制[J].动物营养学报,2019,31(8):3496-3504. MIAO Q X,XIE Y J,TANG X F,et al.The production of oxidative stress and its effect on liver function of livestock and poultry and its mechanism[J].Chinese Journal of Animal Nutrition,2019,31(8):3496-3504.(in Chinese)
[14] 代俊合,谷德权,王超强,等.AST/ALT比值测定在肝炎及肝硬化中的临床意义[J].临床荟萃,2001,16(24):1131. DAI J H,GU D Q,WANG C Q,et al.The clinical significance of AST/ALT ratio determination in hepatitis and liver cirrhosis[J].Clinical Focus,2001,16(24):1131.(in Chinese)
[15] WALTER P,RON D.The unfolded protein response:from stress pathway to homeostatic regulation[J].Science,2011,334(6059):1081-1086.  
[16] HETZ C,MARTINON F,RODRIGUEZ D,et al.The unfolded protein response:integrating stress signals through the stress sensor IRE1α[J].Physiological Reviews,2011,91(4):1219-1243.  
[17] MIURA N,OSAKI Y,NAGASHIMA M,et al.A novel biomarker TERT mRNA is applicable for early detection of hepatoma[J].BMC Gastroenterology,2010,10:46.
[18] 张艳梅.沙葱黄酮对氧化应激小尾寒羊肝脏的保护作用及其机制研究[D].硕士学位论文.呼和浩特:内蒙古农业大学,2019:49-50. ZHANG Y M.Protective effect and mechanism of flavonoids from Allium spp.on the liver of oxidative stress small-tailed Han sheep[D].Master's Thesis.Hohhot:Inner Mongolia Agricultural University 2019:49-50.(in Chinese)
[19] 宓伟,练武,尹淑英,等.山楂原花青素及维生素C对胰岛素抵抗大鼠肝脏氧化应激的影响[J].中草药,2016,47(4):625-629. MI W,LIAN W,YIN S Y,et al.Effects of hawthorn proanthocyanidins and vitamin C on oxidative stress in the liver of insulin-resistant rats[J].Chinese Herbal Medicine,2016,47(4):625-629.(in Chinese)
[20] BAREZ S R,ATAR A M,AGHAEI M.Mechanism of inositol-requiring enzyme 1-alpha inhibition in endoplasmic reticulum stress and apoptosis in ovarian cancer cells[J].Journal of Cell Communication and Signaling,2020,14(4):403-415.  
[21] BAUER C,DUEWELL P,LEHR H A,et al.Protective and aggravating effects of NLRP3 inflammasome activation in IBD models:influence of genetic and environmental factors[J].Digestive Diseases,2012,30(Suppl.1):82-90.
[22] TRIPATHI A,DEBELIUS J,BRENNER D A,et al.Publisher correction:the gut-liver axis and the intersection with the microbiome[J].Nature Reviews Gastroenterology & Hepatology,2018,15(12):785.
[23] PAOLELLA G,MANDATO C,PIERRI L,et al.Gut-liver axis and probiotics:their role in non-alcoholic fatty liver disease[J].World Journal of Gastroenterology,2014,20(42):15518-15531.  
[24] LIN K M,HU W,TROUTMAN T D,et al.IRAK-1 bypasses priming and directly links TLRs to rapid NLRP3 inflammasome activation[J].Proceedings of the National Academy of Sciences of the United States of America,2014,111(2):775-780.  
[25] KOZICKY L K,MENZIES S C,HOTTE N,et al.Intravenous immunoglobulin (IVIg) or IVIg-treated macrophages reduce DSS-induced colitis by inducing macrophage IL-10 production[J].European Journal of Immunology,2019,49(8):1251-1268.
Outlines

/