Association between hepatic sinusoidal obstruction syndrome induced by monocrotaline and neutrophil extracellular traps

doi:10.19803/j.1672-8629.20220667

Abstract

Abstract: Objective To investigate the association between neutrophil extracellular traps (NET) and hepatic sinusoidal obstruction syndrome (HSOS) induced by monocrotaline (MCT). Methods Ten Sprague-Dawley(SD) rats were randomly divided into the normal group and HSOS model group based on body weight, with five in each. The normal group was gavaged with saline while the model group received a single gavage of MCT (90 mg·kg^-1). Forty-eight hours after MCT administration, blood and liver samples were collected. The effects of MCT on histological changes of the liver, alanine aminotransferase and alkaline phosphatase levels, hepatic myeloperoxidase activity, protein expression of citrullinated histone H3 (Cit H3), immunofluorescence staining of NET structure as well as expressions of NET associated genes were investigated. Results In the model group, macroscopic and histological findings revealed liver congestion, sinusoidal alteration, perisinusoidal infiltration of red cells and inflammatory cells, and multifocal hepatocellular necrosis. Furthermore, plasma ALT and ALP levels were significantly increased compared with the normal group(P<0.01). Administration of MCT to rats resulted in a significant elevation of hepatic MPO activity and Cit H3 expression. It NET formation was also observed in the liver lobes in MCT-treated rats. Additionally, the mRNA levels of C-X-C motif chemokine receptor 2(CXCR2), and toll-like receptor 4 (TLR4) were significantly increased in the MCT group (P<0.01). Conclusion NET may be involved in the mechanism responsible for MCT-induced HSOS.

Key words: neutrophil extracellular trap, hepatic sinusoidal obstruction syndrome, monocrotaline, rats

CLC Number:

R979.1
R994

LI Yue, ZHANG Shuang, SUN Xin, LIU Chenghai, QIU Furong. Association between hepatic sinusoidal obstruction syndrome induced by monocrotaline and neutrophil extracellular traps[J]. Chinese Journal of Pharmacovigilance, 2023, 20(2): 121-126.

References

[1] Cooperative Group for Hepatic and Gall Diseases, Chinese Society of Gastroenterology, Chinese Medical Association. Expert consensus on diagnosis and treatment of quinazoline alkaloids-related sinusoidal obstruction syndrome(2017, Nanjing)[J]. Journal of Clinical Hepatology(临床肝胆病杂志), 2017, 33(9): 1627-1637.
[2] DALLE JH, GIRALT SA.Hepatic veno-occlusive disease after hematopoietic stem cell transplantation: risk factors and stratification, prophylaxis, and treatment[J]. Biol Blood Marrow Transplant, 2016, 22(3):400-9.
[3] ZHANG F, ZHOU Y, YANG X, et al.Gynura rhizoma containing pyrrolizidine alkaloids induces the hepatic sinusoidal obstruction syndrome in mice via upregulating fibrosis-related factors[J]. Acta Pharmacological Sinina, 2019, 40(6): 781-789.
[4] ZHU C, REN XH, LIU D, et al.Oxaliplatin-induced hepatic sinusoidal obstruction syndrome[J]. Toxicology, 2021,460: 152882.
[5] ZHUGE YZ, WANG X.Hepatic sinusoidal obstruction syndrome associated with pyrrolizidine alkaloids[J]. Journal of Practical Hepatology(实用肝脏病杂志), 2021, 24(5): 617-620.
[6] ZHU C, REN XH, LIU D, et al.Oxaliplatin-induced hepatic sinusoidal obstruction syndrome[J]. Toxicology, 2021, 460: 152882.
[7] PAUL VS, MATTHEW PL, BALJENDRA K, et al.Transjugular intrahepatic portosystemic shunt complications: prevention and management[J]. Seminars in Interventional Radiology, 2015, 32(2): 123-132.
[8] KOLACZKOWSKA E, JENNE CN, SUREWAARD BGJ, et al.Molecular mechanisms of NET formation and degradation revealed by intravital imaging in the liver vasculature[J]. Nature Communications, 2015, 6: 6673.
[9] HUANG H, TOHME S, AL-KHAFAJI AB, et al.DAMPs-activated neutrophil extracellular trap exacerbates sterile inflammatory liver injury[J]. Hepatology, 2016, 62(2): 600-614.
[10] HILSCHER MB, SEHRAWAT T, VERDUGO JPA, et al.Mechanical stretch increases expression of CXCL1 in liver sinusoidal endothelial cells to recruit neutrophils, generate sinusoidal microthombi, and promote portal hypertension[J]. Gastroenterology, 2019, 157(1): 193-209.
[11] KUMAR A, PALEK R, LISKA V.A critical analysis of experimental animal models of sinusoidal obstruction syndrome[J]. Journal of Clinical and Experimental Hepatology, 2019, 9(3): 345-353.
[12] YANG MB, RUAN JQ, FU PP, et al.Cytotoxicity of pyrrolizidine alkaloid in human hepatic parenchymal and sinusoidal endothelial cells: firm evidence for the reactive metabolites mediated pyrrolizidine alkaloid-induced hepatotoxicity[J]. Chemico-Biological Interactions, 2016, 243: 119-126.
[13] DELEVE LD, MCCUSKEY RS, WANG X, et al.Characterization of a reproducible rat model of hepatic veno-occlusive disease[J]. Hepatology, 1999, 29(6): 1779-1791.
[14] DU JW, ZHANG JM, CHEN XJ, et al.Neutrophil extracellular traps induced by pro-inflammatory cytokines enhance procoagulant activity in NASH patients[J]. Clinics and Research in Hepatology and Gastroenterology, 2022, 46(1): 101697.
[15] NARITA M, HATANO E, TAMAKI M, et al.Dai-kenchu-to attenuates rat sinusoidal obstruction syndrome by inhibiting the accumulation of neutrophils in the liver[J]. Journal of Gastroenterology and Hepatology, 2009, 24: 1051-1057.
[16] PAPAYANNOPOULOS V.Neutrophil extracellular traps in immunity and disease[J]. Nature Reviews Immunology, 2018, 18: 134-147.
[17] SAFFARZADEH M, JUENEMANN C, QUEISSER MA, et al.Neutrophil extracellular traps directly induce epithelial and endothelial cell death: a predominant role of histones[J]. Plos One, 2012, 7(2): e32366.
[18] NARITA M, HATANO E, IKAI I, et al.A phosphodiesterase III inhibitor protects rat liver from sinusoidal obstruction syndrome through heme oxygenase-1 induction[J]. Annals of Surgery, 2009, 249(5): 806-813.
[19] STADTMANN A, ZARBOCK A.CXCR2: from bench to bedside[J]. Frontiers in Immunology, 2012, 3: 263.
[20] WARNATSCH A, IOANNOU M, WANG Q, et al.Inflammation. neutrophil extracellular traps license macrophages for cytokine production in atherosclerosis[J]. Science, 2015, 349(6245): 316-320.