Email Alerts
RSS
Turn off MathJax
Article Contents
Article Navigation >  CHINESE JOURNAL OF BURNS AND WOUNDS  >  > Accepted Manuscript
Xiao Hongyan,Su Shan,An Jiawei,et al.Effects and mechanism of aminoguanidine on acute liver injury in mice[J].Chin J Burns Wounds,2026,42(2):1-10.DOI: 10.3760/cma.j.cn501225-20251016-00431.
Citation: Xiao Hongyan,Su Shan,An Jiawei,et al.Effects and mechanism of aminoguanidine on acute liver injury in mice[J].Chin J Burns Wounds,2026,42(2):1-10.DOI: 10.3760/cma.j.cn501225-20251016-00431.
shu

Effects and mechanism of aminoguanidine on acute liver injury in mice

doi: 10.3760/cma.j.cn501225-20251016-00431
  • 1.

    State Key Laboratory of Trauma and Chemical Poisoning, Department of Wound Infection and Drug, the Army Medical Center, Chongqing 400042, China

  • 2.

    Department of Neurosurgery, the Second Affiliated Hospital of Hainan Medical University, Haikou 570216, Hainan, China

Funds:

Joint Program on Health Science & Technology Innovation of Hainan Province WSJK2025ZD21

More Information
  • Corresponding author: Ouyang Yibin, Email: 55922527@qq.com
  • Received Date: 2025-10-16
    Available Online: 2026-02-09
    Abstract
  •   Objective  To explore the effect and mechanism of aminoguanidine on acute liver injury in mice.  Methods  This was an experimental study. Sixty 6-8-week-old male C57BL/6J mice were randomly divided into blank control group, model group, aminoguanidine control group, and aminoguanidine intervention group, with 15 mice in each group. Mice in model group and aminoguanidine intervention group were induced to acute liver injury by intraperitoneal injection of lipopolysaccharide+D-galactosamine, and mice in aminoguanidine intervention group were intraperitoneally injected with aminoguanidine 12 hours before modeling; mice in aminoguanidine control group were only intraperitoneally injected with an equal amount of aminoguanidine; mice in blank control group were intraperitoneally injected with an equal volume of phosphate buffered saline. At 6 hours after modeling, hematoxylin-eosin staining was used to detect the pathological conditions of liver tissues in blank control group, model group, and aminoguanidine intervention group. According to the kit instructions, a microplate reader was used to determine the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the serum of mice in blank control group, model group and aminoguanidine intervention group, as well as the contents of malondialdehyde (MDA), glutathione (GSH) and iron ions in the liver tissues. TdT-mediated dUTP nick-end labeling (TUNEL) staining was used to detect the cell apoptosis in liver tissues of mice in blank control group, model group, and aminoguanidine intervention group. Reverse transcription polymerase chain reaction was used to detect the mRNA levels of inflammatory factors such as nitric oxide synthase 2 (NOS2), interleukin (IL)-18, IL-1β, and NOD-like receptor pyrin domain-containing protein 3 (NLRP3) in liver tissues of mice in blank control group, model group, aminoguanidine control group, and aminoguanidine intervention group. Western blotting was used to detect the relative expression levels of ferroptosis marker proteins acyl-CoA synthetase long-chain family member 4 (ACSL4), GSH peroxidase 4 (GPX4), and inflammation-related pathway protein NLRP3 and Phosphorylated P65 (p-P65)/P65 ratio in liver tissues of mice in blank control group, model group, aminoguanidine control group, and aminoguanidine intervention group.  Results  At 6 hours after modeling, the liver lobule structure of mice in blank control group was intact, the arrangement of hepatocyte cords was regular, and there was no inflammatory cell infiltration or hepatocyte necrosis. The liver lobule structure of mice in model group was abnormal, the arrangement of hepatocyte cords was disordered, hepatocytes were necrotic, and there was a large amount of inflammatory cell infiltration and liver sinus dilation and congestion. The degree of pathological damage in aminoguanidine intervention group was between that of blank control group and model group. At 6 hours after modeling, compared with that in blank control group, the levels of AST and ALT in the serum of mice in model group were significantly increased (P<0.05); compared with that in model group, the levels of AST and ALT in the serum of mice in aminoguanidine intervention group were significantly decreased (P<0.05). At 6 hours after modeling, compared with that in blank control group, the contents of MDA and iron ions in liver tissues of mice in model group were significantly increased (P<0.05), and the content of GSH was significantly decreased (P<0.05); compared with that in model group, the content of MDA in liver tissues of mice in aminoguanidine intervention group was significantly decreased (P<0.05), and the level of GSH was significantly increased (P<0.05). At 6 hours after modeling, the proportion of TUNEL-positive cells in liver tissues of mice in model group was 26.93%, which was significantly higher than 0.43% in blank control group (P<0.05); the proportion of TUNEL-positive cells in liver tissues of mice in aminoguanidine intervention group was 0.37%, which was significantly lower than that in model group (P<0.05). At 6 hours after modeling, compared with that in blank control group, the aminoguanidine control group of mice showed no statistically significant differences in the mRNA levels of NOS2, IL-18, IL-1β, and NLRP3 in the liver tissues (P>0.05); compared with that in blank control group, the mRNA levels of aforementioned genes in liver tissues of mice in model group were significantly increased (P<0.05); compared with that in model group, the mRNA levels of aforementioned genes in liver tissues of mice in aminoguanidine intervention group were significantly decreased (P<0.05). At 6 hours after modeling, Compared with that in blank control group, the aminoguanidine control group of mice showed no statistically significant differences in the relative expression levels of ACSL4, NLRP3, and GPX4 or p-P65/P65 ratio in liver tissues (P > 0.05); compared with that in blank control group, the relative expression levels of ACSL4 and NLRP3 or p-P65/P65 ratio in the liver tissues of mice in model group were significantly increased (P<0.05), while the relative expression level of GPX4 was significantly decreased (P<0.05). Compared with that in model group, the relative expression levels of ACSL4 and NLRP3 or p-P65/P65 ratio in aminoguanidine intervention group were significantly decreased (P<0.05), and the relative expression level of GPX4 protein was significantly increased (P<0.05).  Conclusions  Aminoguanidine can improve liver function and alleviate acute liver injury induced by lipopolysaccharide+D-galactosamine in mice by down-regulating inflammatory response and inhibiting ferroptosis.

     

    • FullText(HTML)
  • loading
    • References(40)
  • [1]
    HuangS, WangY, XieS, et al. Hepatic TGFβr1 deficiency attenuates lipopolysaccharide/D-galactosamine-induced acute liver failure through inhibiting GSK3β-Nrf2-mediated hepatocyte apoptosis and ferroptosis[J]. Cell Mol Gastroenterol Hepatol, 2022,13(6):1649-1672. DOI: 10.1016/j.jcmgh.2022.02.009.
    [2]
    WangR, ChenY, HanJ, et al. Selectively targeting the AdipoR2-CaM-CaMKII-NOS3 axis by SCM-198 as a rapid-acting therapy for advanced acute liver failure[J]. Nat Commun, 2024,15(1):10690. DOI: 10.1038/s41467-024-55295-7.
    [3]
    YuC, ChenP, MiaoL, et al. The role of the NLRP3 inflammasome and programmed cell death in acute liver injury[J]. Int J Mol Sci, 2023,24(4) :3067. DOI: 10.3390/ijms24043067.
    [4]
    ZhangH, GaoM, WangH, et al. Atractylenolide I prevents acute liver failure in mouse by regulating M1 macrophage polarization[J]. Sci Rep, 2025,15(1):4015. DOI: 10.1038/s41598-025-86977-x.
    [5]
    GaoZ, DaiH, ZhangQ, et al. Hydroxytyrosol alleviates acute liver injury by inhibiting the TNF-α/PI3K/AKT signaling pathway via targeting TNF-α signaling[J]. Int J Mol Sci, 2024,25(23) :12844. DOI: 10.3390/ijms252312844.
    [6]
    YangW, BianS, LiuL. Urantide alleviates lipopolysaccharide/D-galactosamine-induced acute liver failure through upregulating carboxylesterase1f in mice[J]. Front Cell Infect Microbiol, 2025,15:1653725. DOI: 10.3389/fcimb.2025.1653725.
    [7]
    LiuY, ZhaoJ, CongW, et al. Alpinetin pretreatment prevents lipopolysaccharide/D-galactosamine-induced acute liver injury in mice by inhibiting ferroptosis via the Nrf2/SLC7A11/GPX4 pathway[J]. Sci Rep, 2025,15(1):40065. DOI: 10.1038/s41598-025-26588-8.
    [8]
    LongL, ZhangM, QinH, et al. Isorhamnetin protects against D-GalN/LPS-induced acute liver injury in mice through anti-oxidative stress, anti-inflammation, and anti-apoptosis[J]. BMC Complement Med Ther, 2025,25(1):297. DOI: 10.1186/s12906-025-04949-0.
    [9]
    GuoY, GuoW, ChenH, et al. Mechanisms of sepsis-induced acute liver injury: a comprehensive review[J]. Front Cell Infect Microbiol, 2025,15:1504223. DOI: 10.3389/fcimb.2025.1504223.
    [10]
    CaiX, DengJ, WangL, et al. Gallium-doped MXene nanozymes protect liver through multi-death pathway blockade and hepatocyte regeneration[J]. Adv Sci (Weinh), 2026:e09079. DOI: 10.1002/advs.202509079.
    [11]
    ZhengS, GaoY, CaoH, et al. Sophoricoside ameliorates LPS/D-GalN-induced acute liver failure by inhibiting ferroptosis via activation of the Nrf2/GPX4 signaling pathway[J]. Phytomedicine, 2026,150:157716. DOI: 10.1016/j.phymed.2025.157716.
    [12]
    CormanB, DuriezM, PoitevinP, et al. Aminoguanidine prevents age-related arterial stiffening and cardiac hypertrophy[J]. Proc Natl Acad Sci U S A, 1998,95(3):1301-1306. DOI: 10.1073/pnas.95.3.1301.
    [13]
    ThornalleyPJ. Use of aminoguanidine (Pimagedine) to prevent the formation of advanced glycation endproducts[J]. Arch Biochem Biophys, 2003,419(1):31-40. DOI: 10.1016/j.abb.2003.08.013.
    [14]
    KosticT, PopovićD, PerisicZ, et al. The hepatoprotective effect of aminoguanidine in acute liver injury caused by CCl4 in rats[J]. Biomed Pharmacother, 2022,156:113918. DOI: 10.1016/j.biopha.2022.113918.
    [15]
    PatrycyM, JanickaM, KaucA, et al. The role of nitric oxide in HSV-1 infection: the use of an inducible nitric synthase inhibitor aminoguanidine to treat neuroinflammation[J]. Microorganisms, 2025,13(10) :2222. DOI: 10.3390/microorganisms13102222.
    [16]
    TIdSilva, TdCFernandes, de Sá MoreiraET, et al. Role of Nitric oxide synthase Ⅱ in cognitive impairment due to experimental cerebral malaria[J]. Nitric Oxide, 2024,153:41-49. DOI: 10.1016/j.niox.2024.10.002.
    [17]
    Díez-FernándezC, SanzN, AlvarezAM, et al. Influence of aminoguanidine on parameters of liver injury and regeneration induced in rats by a necrogenic dose of thioacetamide[J]. Br J Pharmacol, 1998,125(1):102-108. DOI: 10.1038/sj.bjp.0702014.
    [18]
    MahmoudMF, ZakariaS, FahmyA. Can chronic nitric oxide inhibition improve liver and renal dysfunction in bile duct ligated rats?[J]. Adv Pharmacol Sci, 2015,2015:298792. DOI: 10.1155/2015/298792.
    [19]
    YangS, KuangG, ZhangL, et al. Mangiferin attenuates LPS/D-GalN-induced acute liver injury by promoting HO-1 in kupffer cells[J]. Front Immunol, 2020,11:285. DOI: 10.3389/fimmu.2020.00285.
    [20]
    FengJ, YeS, HaiB, et al. RNF115/BCA2 deficiency alleviated acute liver injury in mice by promoting autophagy and inhibiting inflammatory response[J]. Cell Death Dis, 2023,14(12):855. DOI: 10.1038/s41419-023-06379-7.
    [21]
    陈立, 李东良. 免疫检查点抑制剂相关肝损伤临床诊治的若干问题与思考[J]. 中华肝脏病杂志,2025,33(8):806-810.DOI: 10.3760/cma.j.cn501113-20240103-00005.
    [22]
    Rastegar-MoghaddamSH, KiumarsiZ, MiraniA, et al. Aminoguanidine improved liver function and attenuated oxidative stress in hypothyroid rats by propylthiouracil[J]. Adv Biomed Res, 2025,14:64. DOI: 10.4103/abr.abr_538_24.
    [23]
    PastenC, LozanoM, RoccoJ, et al. Aminoguanidine prevents the oxidative stress, inhibiting elements of inflammation, endothelial activation, mesenchymal markers, and confers a renoprotective effect in renal ischemia and reperfusion injury[J]. Antioxidants (Basel), 2021,10(11):1724.DOI: 10.3390/antiox10111724.
    [24]
    AhmedAF, MahmoudMF, OufMA, et al. Aminoguanidine potentiates the hepatoprotective effect of silymarin in CCL4 treated rats[J]. Ann Hepatol, 2011,10(2):207-215.
    [25]
    徐小惠,冯金梅,罗颖,等. NDUFA13过表达可减轻 CCl4诱导的小鼠肝纤维化:基于抑制NLRP3活化[J]. 南方医科大学学报, 2024,44(2):201-209. DOI: 10.12122/j.issn.1673-4254.2024.02.01.
    [26]
    MaY, SongX, MaT, et al. Aminoguanidine inhibits IL-1β-induced protein expression of iNOS and COX-2 by blocking the NF-κB signaling pathway in rat articular chondrocytes[J]. Exp Ther Med, 2020,20(3):2623-2630. DOI: 10.3892/etm.2020.9021.
    [27]
    刘潇, 蒙健林, 王明刚, 等. 解毒化瘀升散方抑制NLRP3信号通路缓解慢加急性肝衰竭大鼠炎症损伤的实验研究[J]. 中华肝脏病杂志,2024,32(4):354-362.DOI: 10.3760/cma.j.cn501113-20230816-00060.
    [28]
    EkongU, ZengS, DunH, et al. Blockade of the receptor for advanced glycation end products attenuates acetaminophen-induced hepatotoxicity in mice[J]. J Gastroenterol Hepatol, 2006,21(4):682-688. DOI: 10.1111/j.1440-1746.2006.04225.x.
    [29]
    ZengS, FeirtN, GoldsteinM, et al. Blockade of receptor for advanced glycation end product (RAGE) attenuates ischemia and reperfusion injury to the liver in mice[J]. Hepatology, 2004,39(2):422-432. DOI: 10.1002/hep.20045.
    [30]
    GoodwinM, HerathC, JiaZ, et al. Advanced glycation end products augment experimental hepatic fibrosis[J]. J Gastroenterol Hepatol, 2013,28(2):369-376. DOI: 10.1111/jgh.12042.
    [31]
    WeinhageT, WirthT, SchützP, et al. The Receptor for advanced glycation endproducts (RAGE) contributes to severe inflammatory liver injury in mice[J]. Front Immunol, 2020,11:1157. DOI: 10.3389/fimmu.2020.01157.
    [32]
    ReddyVP, AryalP, DarkwahEK. Advanced glycation end products in health and disease[J]. Microorganisms, 2022,10(9):1848. DOI: 10.3390/microorganisms10091848.
    [33]
    龚政, 张筱薇, 李笑眉, 等. 黄芩苷对高糖处理的小鼠成纤维细胞铁死亡的作用及其机制[J].中华烧伤与创面修复杂志,2025,41(3):277-285. DOI: 10.3760/cma.j.cn501225-20240425-00151.
    [34]
    CapellettiMM, ManceauH, PuyH, et al. Ferroptosis in liver diseases: an overview[J]. Int J Mol Sci, 2020,21(14):4908. DOI: 10.3390/ijms21144908.
    [35]
    SunY, ZhaoB, LiH, et al. Overview of ferroptosis and pyroptosis in acute liver failure[J]. World J Gastroenterol, 2024,30(34):3856-3861. DOI: 10.3748/wjg.v30.i34.3856.
    [36]
    GuoY, ChenH, SunJ, et al. Maresin1 inhibits ferroptosis via the Nrf2/SLC7A11/GPX4 pathway to protect against sepsis-induced acute liver injury[J]. J Inflamm Res, 2024,17:11041-11053. DOI: 10.2147/JIR.S498775.
    [37]
    WangJ, LiaoL, MiaoB, et al. Deciphering the role of the MALT1-RC3H1 axis in regulating GPX4 protein stability[J]. Proc Natl Acad Sci U S A, 2025,122(1):e2419625121. DOI: 10.1073/pnas.2419625121.
    [38]
    张浩, 官浩, 汪宇航, 等. 铁死亡在大鼠烧冲复合伤合并急性肺损伤中的作用及其机制[J].中华烧伤与创面修复杂志,2024,40(11):1034-1042. DOI: 10.3760/cma.j.cn501225-20240528-00199.
    [39]
    DollS, PronethB, TyurinaYY, et al. ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition[J]. Nat Chem Biol, 2017,13(1):91-98. DOI: 10.1038/nchembio.2239.
    [40]
    HeY, WangJ, YingC, et al. The interplay between ferroptosis and inflammation: therapeutic implications for cerebral ischemia-reperfusion[J]. Front Immunol, 2024,15:1482386. DOI: 10.3389/fimmu.2024.1482386.
    • 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(7)  / Tables(2)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (103) PDF downloads(10) Cited by()
    Proportional views
    Related

    Copyright © Chinese Journal of Burns京ICP备07035254号-14

    E-mail：shaoshangzazhi@163.com

    Website：https://zhsszz.xml-journal.net/

    Supported by: Beijing Renhe Information Technology Co. Ltd    

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return