NF-κB and NLRP3 gene expression changes during warm hepatic ischemia-reperfusion in rats with and without silibinin
Gastroenterology and Hepatology from Bed to Bench,
Vol. 14 No. 3 (2021),
26 April 2021
,
Page 267-275
https://doi.org/10.22037/ghfbb.v14i3.2171
Abstract
Aim: This research examined silibinin's anti-inflammatory outcomes on the NOD-like receptor protein-3 (NLRP3) and NF-κB gene expression, which plays a notable role in inciting inflammatory pathways.
Background: Hepatic ischemia-reperfusion (I/R) is a common phenomenon in many clinical cases, including liver surgery and transplantation. Inflammatory mediators are vital contributors to the expansion of hepatic damage after I/R injury (I/RI), and therefore, targeting inflammation is a considerable candidate for the management of hepatic I/RI and its complications.
Methods: Thirty-two male Wistar rats were divided equally into four groups: 1) Control (Vehicle) group, in which rats underwent laparotomy and received normal saline; 2) SILI group, in which rats underwent laparotomy, and 30 mg/kg silibinin was injected intraperitoneal (IP); 3) I/R group, in which rats underwent I/R and received normal saline; and 4) I/R + SILI group, who encountered I/R after laparotomy and received silibinin. After one hour of ischemia and three hours of reperfusion, blood and liver tissue samples were assembled for future biochemical, histological, and gene expression studies.
Results: In vivo analysis attested that serum AST and ALT activities were significantly lessened by silibinin in the SILI + I/R group (p <0.001). Silibinin ameliorated inflammatory liver tissue injuries, including neutrophil and macrophage infiltration, hepatocyte degeneration, cytoplasmic vacuolation, vascular endothelial damages, and sinusoid dilation observed in the I/R group. During I/R, NLRP3 and NF-κB gene expression showed a significant increment compared to the control group (p <0.001), which could be alleviated by silibinin (p <0.01).
Conclusion: The results evidence that adjusting the expression of NLRP3 and NF-κB genes during I/R is probably one of the mechanisms of the anti-inflammatory effects of silibinin.
Keywords: Ischemia, NF-Κb, NLRP3, Reperfusion, Silibinin.
(Please cite as: Zarpou S, Mosavi H, Bagheri A, Malekzadeh Shafaroudi M, Khonakdar-Tarsi A. NF-κB and NLRP3 gene expression changes during warm hepatic ischemia-reperfusion in rats with and without silibinin. Gastroenterol Hepatol Bed Bench 2021;14(3):267-275).
- Keywords: Ischemia, NF-κB, NLRP3, Reperfusion, Silibinin.
How to Cite
References
Konishi T, Lentsch AB. Hepatic ischemia/reperfusion: mechanisms of tissue injury, repair, and regeneration. Gene Exp J Liver Res 2017;17:277-87.
Freitas SH, Doria RG, Bueno RS, Rocha WB, Filho JR, Moraes JR, et al. Evaluation of potential changes in liver and lung tissue of rats in an ischemia-reperfusion injury model (modified pringle maneuver). PLoS One 2017;12:e0178665.
Miah MK, Bickel U, Mehvar R. Effects of hepatic ischemia-reperfusion injury on the blood-brain barrier permeability to [14 C] and [13 C] sucrose. Metab Brain Dis 2017;32:1903-12.
Jochmans I, Meurisse N, Neyrinck A, Verhaegen M, Monbaliu D, Pirenne J. Hepatic ischemia/reperfusion injury associates with acute kidney injury in liver transplantation: prospective cohort study. Liver Transplant 2017;23:634-44.
van Golen RF, Reiniers MJ, Marsman G, Alles LK, van Rooyen DM, Petri B, et al. The damage-associated molecular pattern HMGB1 is released early after clinical hepatic ischemia/reperfusion. Biochim Biophys Acta Mol Basis Dis 2019;1865:1192-200.
Wu Y, Zhang W, Li M, Cao D, Yang X, Gong J. Nobiletin ameliorates ischemia–reperfusion injury by suppressing the function of Kupffer cells after liver transplantation in rats. Biomed Pharmacother 2017;89:732-41.
Li SP, Wang FF, Zhang WK, Bian MZ, Zhang SY, Yan H, et al. Characteristics of Changes in Inflammatory Cytokines as a Function of Hepatic Ischemia-Reperfusion Injury Stage in Mice. Inflammation 2019;42:2139-47.
Abazari O, Divsalar A, Ghobadi R. Inhibitory effects of oxali-Platin as a chemotherapeutic drug on the function and structure of bovine liver catalase. J Biomol Struct Dyn 2020;38:609-15.
Li J, Li R, Lv G, Liu H. The mechanisms and strategies to protect from hepatic ischemia-reperfusion injury. Eur Rev Med Pharmacol Sci 2015;19:2036-47.
de Zoete MR, Palm NW, Zhu S, Flavell RA. Inflammasomes. Cold Spring Harb Perspect Biol 2014;6:a016287.
Broz P, Dixit VM. Inflammasomes: mechanism of assembly, regulation and signalling. Nat Rev Immunol 2016;16:407-20.
Bortolotti P, Faure E, Kipnis E. Inflammasomes in tissue damages and immune disorders after trauma. Front Immunol 2018;9:1900.
Jo EK, Kim JK, Shin DM, Sasakawa C. Molecular mechanisms regulating NLRP3 inflammasome activation. Cell Mol Immunol 2016;13:148-59.
Asadi A, Nezhad DY, Javazm AR, Khanicheragh P, Mashouri L, Shakeri F, et al. In vitro Effects of Curcumin on Transforming Growth Factor-β-mediated Non-Smad Signaling Pathway, Oxidative Stress, and Pro‐inflammatory Cytokines Production with Human Vascular Smooth Muscle Cells. Iran J Allergy Asthma Immunol 2019:1-10.
Kim HY, Kim SJ, Lee SM. Activation of NLRP 3 and AIM2 inflammasomes in Kupffer cells in hepatic ischemia/reperfusion. FEBS J 2015;282:259-70.
Musavi H, Abazari O, Safaee MS, Variji A, Koohshekan B, Kalaki-Jouybari F, et al. Mechanisms of COVID-19 Entry into the Cell: Potential Therapeutic Approaches based on Virus Entry Inhibition in COVID-19 Patients with Underlying Diseases. Iran J Allergy Asthma Immunol 2021:1-13.
Wang L, Li N, Lin D, Zang Y. Curcumin protects against hepatic ischemia/reperfusion induced injury through inhibiting TLR4/NF-κB pathway. Oncotarget 2017;8:65414.
Patel P, Drayman N, Liu P, Bilgic M, Tay S. Deep learning reveals hidden variables underlying NF-κB activation in single cells. bioRxiv 2019:687848.
Afonina IS, Zhong Z, Karin M, Beyaert R. Limiting inflammation—the negative regulation of NF-κB and the NLRP3 inflammasome. Nat Immunol 2017;18:861.
Boaru SG, Borkham-Kamphorst E, Van de Leur E, Lehnen E, Liedtke C, Weiskirchen R. NLRP3 inflammasome expression is driven by NF-κB in cultured hepatocytes. Biochem Biophys Res Commun 2015;458:700-6.
Abazari O, Shafaei Z, Divsalar A, Eslami-Moghadam M, Ghalandari B, Saboury AA, et al. Interaction of the synthesized anticancer compound of the methyl-glycine 1, 10-phenanthroline platinum nitrate with human serum albumin and human hemoglobin proteins by spectroscopy methods and molecular docking. J Iran Chem Soc 2020; 17: 1-14.
Akbari-Kordkheyli V, Azizi S, Khonakdar-Tarsi A. Effects of silibinin on hepatic warm ischemia-reperfusion injury in the rat model. Iran J Basic Med Sci 2019;22:789.
Qajari NM, Shafaroudi MM, Gholami M, Khonakdar-Tarsi A. Silibinin treatment results in reducing OPA1&MFN1 genes expression in a rat model hepatic ischemia–reperfusion. Mol Biol Rep 2020:1-10.
Zhu XX, Ding YH, Wu Y, Qian LY, Zou H, He Q. Silibinin: a potential old drug for cancer therapy. Expert Rev Clin Pharmacol 2016;9:1323-30.
Yang N, Jia X, Wang D, Wei C, He Y, Chen L, et al. Silibinin as a natural antioxidant for modifying polysulfone membranes to suppress hemodialysis-induced oxidative stress. J Memb Sci 2019;574:86-99.
Tajmohammadi A, Razavi BM, Hosseinzadeh H. Silybum marianum (milk thistle) and its main constituent, silymarin, as a potential therapeutic plant in metabolic syndrome: A review. Phytother Res 2018;32:1933-49.
Chen YH, Lin H, Wang Q, Hou JW, Mao ZJ, Li YG. Protective role of silibinin against myocardial ischemia/reperfusion injury-induced cardiac dysfunction. Int J Biol Sci 2020;16:1972.
Abazari O, Shafaei Z, Divsalar A, Eslami-Moghadam M, Ghalandari B, Saboury AA. Probing the biological evaluations of a new designed Pt (II) complex using spectroscopic and theoretical approaches: Human hemoglobin as a target. J Biomol Struct Dyn 2016;34:1123-31.
Musavi H, Abazari O, Barartabar Z, Kalaki-Jouybari F, Hemmati-Dinarvand M, Esmaeili P, et al. The benefits of Vitamin D in the COVID-19 pandemic: biochemical and immunological mechanisms. Arch Physiol Biochem 2020:1-9.
Chen Z, Ding T, Ma CG. Dexmedetomidine (DEX) protects against hepatic ischemia/reperfusion (I/R) injury by suppressing inflammation and oxidative stress in NLRC5 deficient mice. Biochem Biophys Res Commun 2017;493:1143-50.
Olthof PB, van Golen RF, Meijer B, van Beek AA, Bennink RJ, Verheij J, et al. Warm ischemia time-dependent variation in liver damage, inflammation, and function in hepatic ischemia/reperfusion injury. Biochim Biophys Acta Mol Basis Dis 2017;1863:375-85.
Cannistrà M, Ruggiero M, Zullo A, Gallelli G, Serafini S, Maria M, et al. Hepatic ischemia reperfusion injury: A systematic review of literature and the role of current drugs and biomarkers. Int J Surg 2016;33:S57-70.
Shafaei Z, Abazari O, Divsalar A, Ghalandari B, Poursoleiman A, Saboury AA, et al. Effect of a Synthesized Amyl-Glycine1, 10-Phenanthroline Platinum Nitrate on Structure and Stability of Human Blood Carrier Protein, Albumin: Spectroscopic and Modeling Approaches. J Fluoresc 2017;27:1829-38.
Inoue Y, Shirasuna K, Kimura H, Usui F, Kawashima A, Karasawa T, et al. NLRP3 regulates neutrophil functions and contributes to hepatic ischemia–reperfusion injury independently of inflammasomes. J Immunol 2014;192:4342-51.
Guo Z, Yu S, Chen X, Ye R, Zhu W, Liu X. NLRP3 is involved in ischemia/reperfusion injury. CNS Neurol Disord Drug Targets 2016;15:699-712.
Zare Z, Dizaj TN, Lohrasbi A, Sheikhalishahi ZS, Asadi A, Zakeri M, et al. Silibinin inhibits TGF-β-induced MMP-2 and MMP-9 through Smad Signaling pathway in colorectal cancer HT-29 cells. Basic Clin Cancer Res 2020;12:79-88.
Serasanambati M, Chilakapati SR. Function of nuclear factor kappa B (NF-kB) in human diseases-a review. South Indian Journal of Biological Sciences 2016;2:368-87.
Huang H, Tohme S, Al‐Khafaji AB, Tai S, Loughran P, Chen L, et al. Damage‐associated molecular pattern–activated neutrophil extracellular trap exacerbates sterile inflammatory liver injury. Hepatology 2015;62:600-14.
Sadatomo A, Inoue Y, Ito H, Karasawa T, Kimura H, Watanabe S, et al. Interaction of neutrophils with macrophages promotes IL-1β maturation and contributes to hepatic ischemia–reperfusion injury. J Immunol 2017;199:3306-15.
He Q, Li Z, Wang Y, Hou Y, Li L, Zhao J. Resveratrol alleviates cerebral ischemia/reperfusion injury in rats by inhibiting NLRP3 inflammasome activation through Sirt1-dependent autophagy induction. Int Immunopharmacol 2017;50:208-15.
Lingappan K. NF-κB in oxidative stress. Curr Opin Toxicol 2018;7:81-6.
Zare Z, Dizaj TN, Lohrasbi A, Sheikhalishahi ZS, Panji M, Hosseinabadi F, et al. The Effect of Piperine on MMP-9, VEGF, and E-cadherin Expression in Breast Cancer MCF-7 Cell Line. Basic Clin Cancer Res 2020;12:112-9.
Kim BR, Seo HS, Ku JM, Kim GJ, Jeon CY, Park JH, et al. Silibinin inhibits the production of pro-inflammatory cytokines through inhibition of NF-κB signaling pathway in HMC-1 human mast cells. Inflamm Res 2013;62:941-50.
Zhang B, Wang B, Cao S, Wang Y, Wu D. Silybin attenuates LPS-induced lung injury in mice by inhibiting NF-κB signaling and NLRP3 activation. Int J Mol Med 2017;39:1111-8.
Matias ML, Gomes VJ, Romao-Veiga M, Ribeiro VR, Nunes PR, Romagnoli GG, et al. Silibinin downregulates the NF-κB pathway and NLRP1/NLRP3 inflammasomes in monocytes from pregnant women with preeclampsia. Molecules 2019;24:1548.
Kyriakopoulos G, Tsaroucha AK, Valsami G, Lambropoulou M, Kostomitsopoulos N, Christodoulou E, et al. Silibinin improves TNF-α and M30 expression and histological parameters in rat kidneys after hepatic ischemia/reperfusion. J Invest Surg 2018;31:201-9.
- Abstract Viewed: 18 times
- PDF Downloaded: 21 times