Volume 10 Issue 1
Jan.  2019
Turn off MathJax
Article Contents
Article Navigation >  ORGAN TRANSPLANTATION  > 2019  >  10(1): 50-54, 87
Huang Yiming, Wang Li, Li Jinjun, et al. Establishment of acute liver failure models induced by D-galactosamine in non-human primates[J]. ORGAN TRANSPLANTATION, 2019, 10(1): 50-54, 87. doi: 10.3969/j.issn.1674-7445.2019.01.007
Citation: Huang Yiming, Wang Li, Li Jinjun, et al. Establishment of acute liver failure models induced by D-galactosamine in non-human primates[J]. ORGAN TRANSPLANTATION, 2019, 10(1): 50-54, 87. doi: 10.3969/j.issn.1674-7445.2019.01.007
shu

Establishment of acute liver failure models induced by D-galactosamine in non-human primates

doi: 10.3969/j.issn.1674-7445.2019.01.007

  • Department of Hepatic Surgery, Liver Transplantation Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou 510630, China

More Information
  • Corresponding author: Yang Yang, E-mail:yysysu@163.com
  • Received Date: 2018-10-28
    Available Online: 2021-01-19
  • Publish Date: 2019-01-15
    Abstract
  •   Objective  To evaluate the effect of different doses of D-galactosamine (D-Gal) on non-human primate cynomolgus monkey and to establish a monkey model with different degree of acute liver failure (ALF).  Methods  Twelve cynomolgus monkeys were evenly divided into the low-, medium- and high-dose groups (n=4) with a dosage of 0.23, 0.25 and 0.27 g/kg, respectively. In each group, the corresponding dose of D-Gal solution was injected into the monkeys through the forearm vein at one time in a sober state (without anesthesia). The survival time of the cynomolgus monkeys was recorded. Digestive tract and hepatic encephalopathy symptoms were observed. Vital signs were measured at 0 h before and 12, 24, 36, 48, 60, 72, 96, 120 and 144 h after D-Gal administration. Alanine transaminase (ALT), total bilirubin (TB), prothrombin time (PT), blood ammonia and other parameters were detected from the blood samples. The liver tissues were prepared for hematoxylin-eosin (HE) staining to observe the pathological changes.  Results  All cynomolgus monkeys in the low-dose group survived and transient liver injury was noted without the hepatic encephalopathy symptoms. At 60 h after D-Gal administration, the liver function and coagulation indexes reached the peak, gradually recovered and then basically returned to the normal range at 120 h. In the medium-dose group, the course of disease was relatively slow and gradually recovered after the appearance of severe liver damage and hepatic encephalopathy symptoms and only one animal died. All cynomolgus monkeys in the high-dose group died after developing hepatic encephalopathy symptoms and severe liver damage with a mean survival time of (72±13) h. Pathological examination of liver tissue demonstrated that scattered liver cell necrosis and inflammatory cell infiltration were observed in the liver tissues of the low-dose group. In the medium- and high-dose groups, the hepatic lobule structure was not clear, and the liver cell necrosis in flakes accompanied by evident hemorrhage were documented.  Conclusions  The D-Gal dosage in the medium- and high-dose groups meet the standards of the ALF model. The degree of ALF in the medium-dose group is relatively slight, which is beneficial to the implementation of liver transplantation. ALF in the high-dose group is relatively severe, which is suitable for the evaluation of the clinical efficacy of therapeutic options.

     

    • FullText(HTML)
  • loading
    • References(19)
  • [1]
    WANG YH, WU DB, CHEN B, et al. Progress in mesenchymal stem cell-based therapy for acute liver failure[J]. Stem Cell Res Ther, 2018, 9(1):227. DOI: 10.1186/s13287-018-0972-4.
    [2]
    CARDOSO FS, MARCELINO P, BAGULHO L, et al. Acute liver failure: an up-to-date approach[J]. J Crit Care, 2017, 39:25-30. DOI: 10.1016/j.jcrc.2017.01.003.
    [3]
    ISIK A, FIRAT D. Bilateral intra-areolar polythelia[J]. Breast J, 2018, 24(1):89-90. DOI: 10.1111/tbj.12838.
    [4]
    DEFTEREVOS G, NASTOS C, PAPALOIS A, et al. Peritoneal albumin dialysis as a novel approach for liver support: study in a porcine model of acute hepatic failure[J]. Artif Organs, 2016, 40(8):755-764. DOI: 10.1111/aor.12687.
    [5]
    SANG JF, SHI XL, HAN B, et al. Intraportal mesenchymal stem cell transplantation prevents acute liver failure through promoting cell proliferation and inhibiting apoptosis[J]. Hepatobiliary Pancreat Dis Int, 2016, 15(6):602-611. doi: 10.1016/S1499-3872(16)60141-8
    [6]
    桑剑锋, 马虎成, 施晓雷, 等.巴马小型猪85%肝切除术后急性肝功能衰竭模型的建立[J].中国实验动物学报, 2017, 25(2):174-180.DOI: 10.3969/j.issn.1005-4847.2017.02.011.

    SANG JF, MA HC, SHI XL, et al. Establishment of a porcine model of acute liver failure after 85% hepatectomy[J]. Acta Lab Anim Sci Sin, 2017, 25(2):174-180. DOI: 10.3969/j.issn.1005-4847.2017.02.011.
    [7]
    FLAMM SL, YANG YX, SINGH S, et al. American gastroenterological association institute guidelines for the diagnosis and management of acute liver failure[J]. Gastroenterology, 2017, 152(3):644-647. DOI: 10.1053/j.gastro.2016.12.026.
    [8]
    FENG L, CAI L, HE GL, et al. Novel D-galactosamine-induced cynomolgus monkey model of acute liver failure[J]. World J Gastroenterol, 2017, 23(42):7572-7583. DOI: 10.3748/wjg.v23.i42.7572.
    [9]
    CAI L, WENG J, FENG L, et al. Establishment of a novel simplified surgical model of acute liver failure in the cynomolgus monkey[J]. Biomed Res Int, 2016:3518989. DOI: 10.1155/2016/3518989.
    [10]
    时红波, 时红林, 张向颖, 等.细胞自噬在D-氨基半乳糖/脂多糖诱导的小鼠急性肝损伤模型中的保护作用及机制[J].临床肝胆病杂志, 2017, 33(2):329-333. DOI: 10.3969/j.issn.1001-5256.2017.02.027.

    SHI HB, SHI HL, ZHANG XY, et al. Protective effect of autophagy in mice with acute liver injury induced by D-galactosamine/lipopolysaccharide and related mechanisms[J]. J Clin Hepatol, 2017, 33(2):329-333. DOI: 10.3969/j.issn.1001-5256.2017.02.027.
    [11]
    HE GL, FENG L, CAI L, et al. Artificial liver support in pigs with acetaminophen-induced acute liver failure[J]. World J Gastroenterol, 2017, 23(18):3262-3268. DOI: 10.3748/wjg.v23.i18.3262.
    [12]
    NING Y, KIM JK, MIN HK, et al. Cholesterol metabolites alleviate injured liver function and decrease mortality in an LPS-induced mouse model[J]. Metabolism, 2017, 71:83-93. DOI: 10.1016/j.metabol.2016.12.007.
    [13]
    TUÑÓN MJ, ALVAREZ M, CULEBRAS JM, et al. An overview of animal models for investigating the pathogenesis and therapeutic strategies in acute hepatic failure[J]. World J Gastroenterol, 2009, 15(25):3086-3098. doi: 10.3748/wjg.15.3086
    [14]
    MAES M, VINKEN M, JAESCHKE H. Experimental models of hepatotoxicity related to acute liver failure[J]. Toxicol Appl Pharmacol, 2016, 290:86-97. DOI: 10.1016/j.taap.2015.11.016.
    [15]
    GLORIOSO JM, MAO SA, RODYSILL B, et al. Pivotal preclinical trial of the spheroid reservoir bioartificial liver[J]. J Hepatol, 2015, 63(2):388-398. DOI: 10.1016/j.jhep.2015.03.021.
    [16]
    ZHOU P, SHAO L, ZHAO L, et al. Efficacy of fluidized bed bioartificial liver in treating fulminant hepatic failure in pigs: a metabolomics study[J]. Sci Rep, 2016, 6:26070. DOI: 10.1038/srep26070.
    [17]
    BUTTERWORTH RF. Pathogenesis of hepatic encephalopathy and brain edema in acute liver failure[J]. J Clin Exp Hepatol, 2015, 5(Suppl 1):S96-S103. DOI: 10.1016/j.jceh.2014.02.004.
    [18]
    曾艳丽, 高飞, 魏君峰, 等.血栓弹力图评价慢加急性肝衰竭患者的凝血功能及预后研究[J].中华肝脏病杂志, 2017, 25(1):32-37.DOI: 10.3760/cma.j.issn.1007-3418.2017.01.008.

    ZENG YL, GAO F, WEI JF, et al. Value of thromboelastography in evaluating coagulation function and prognosis in patients with acute-on-chronic liver failure[J]. Chin J Hepatol, 2017, 25(1):32-37. DOI: 10.3760/cma.j.issn.1007-3418.2017.01.008.
    [19]
    RAMANATHAN R, PETTINATO G, BEESTON JT, et al. Transplantation of human stem cell-derived hepatocytes in an animal model of acute liver failure[J]. Surgery, 2015, 158(2):349-359. DOI: 10.1016/j.surg.2015.04.014.
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(2)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (147) PDF downloads(15) Cited by()
    Proportional views
    Related

    WeChat Subscription Account

    Wechat Service Account

    Contact Us
    • Tel：020-38736410
    • Email: organtranspl@163.com
    • Address：The Third Affiliated Hospital of Sun Yat-sen University, No. 600, Tianhe Road, Tianhe District, Guangzhou
    • Editorial Office of Organ Transplantation  粤ICP备2021030844号
    Links

    Supported by: Beijing Renhe Information Technology Co. Ltd    

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return