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Silibinin treatment results in reducing OPA1&MFN1 genes expression in a rat model hepatic ischemia–reperfusion

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Abstract

The mitochondrial damage has a pivotal role in triggering apoptosis and cell death. This study assessed the effect of silibinin on optical atrophy-1 (OPA1) and mitofusin-1 (MFN1) gene expression in liver tissue during hepatic warm ischemia–reperfusion (IR). Four groups of rats, eight rats each were designed: Vehicle: the rats received normal saline and encountered to laparotomy, Sili: silibinin (60 mg/kg) was administered to animals, IR: the rats received the normal saline and insulted by liver IR procedure, and IR + Sili: silibinin was injected to rats. All groups were subjected to the same process of injection of the solvent or silibinin (30 min before laparotomy or ischemia and immediately after the reperfusion), intraperitoneally (IP). After 3 h of reperfusion, blood and liver tissue samples were collected for future examinations. Our results showed no significant differences between the Vehicle and Sili groups in all assessed parameters. In IR + Sili, the increased serum levels of AST and ALT in comparison with the control group were markedly reduced by silibinin treatment. Silibinin lowered the elevated expression of OPA1 and MFN1 mRNAs in the IR group. Histology revealed silibinin could decline tissue degeneration compared to the IR group. Electron microscopy of control and silibinin groups showed no fusion of mitochondria and tissue degradation both of which were observed in the IR group. The extent of tissue destruction and mitochondrial fusion decreased significantly with silibinin treatment. Silibinin has a protective effect on liver cells against IR induced injuries by preserving mitochondrial membrane.

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References

  1. Colletti LM, Kunkel SL, Walz A, Burdick MD, Kunkel RG, Wilke CA, Strieter RM (1996) The role of cytokine networks in the local liver injury following hepatic ischemia/reperfusion in the rat. Hepatology 23:506–514

    Article  CAS  Google Scholar 

  2. Lentsch AB, Kato A, Yoshidome H, McMasters KM, Edwards MJ (2000) Inflammatory mechanisms and therapeutic strategies for warm hepatic ischemia/reperfusion injury. Hepatology 32:169–173

    Article  CAS  Google Scholar 

  3. Inal M, Kanbak G, Adali M (2006) Prevention of ischemia-reperfusion-induced oxidative injury in liver by allopurinol and pentoxifylline. Transplantationsmedizin 18:29

    Google Scholar 

  4. Caraceni P, Domenicali M, Vendemiale G, Grattagliano I, Pertosa A, Nardo B, Morselli-Labate AM, Trevisani F, Palasciano G, Altomare E (2005) The reduced tolerance of rat fatty liver to ischemia reperfusion is associated with mitochondrial oxidative injury1. J Surg Res 124:160–168

    Article  CAS  Google Scholar 

  5. Ates E, Genç E, Erkasap N, Erkasap S, Akman S, Firat P, Emre S, Kiper H (2002) Renal protection by brief liver ischemia in rats1. Transplantation 74:1247–1251

    Article  Google Scholar 

  6. Van der Bliek AM, Shen Q, Kawajiri S (2013) Mechanisms of mitochondrial fission and fusion. Cold Spring Harb Perspect Biol 5:a011072

    PubMed  PubMed Central  Google Scholar 

  7. Škottová N, Kazdová L, Oliyarnyk O, Večeřa R, Sobolová L, Ulrichová J (2004) Phenolics-rich extracts from Silybum marianum and Prunella vulgaris reduce a high-sucrose diet induced oxidative stress in hereditary hypertriglyceridemic rats. Pharmacol Res 50:123–130

    Article  Google Scholar 

  8. Kang JS, Jeon YJ, Park S-K, Yang K-H, Kim HM (2004) Protection against lipopolysaccharide-induced sepsis and inhibition of interleukin-1β and prostaglandin E2 synthesis by silymarin. Biochem Pharmacol 67:175–181

    Article  CAS  Google Scholar 

  9. Akbari-Kordkheyli V, Azizi S, Khonakdar-Tarsi A (2019) Effects of silibinin on hepatic warm ischemia-reperfusion injury in the rat model. Iran J Basic Med Sci 22:789–796

    PubMed  PubMed Central  Google Scholar 

  10. Ghobadi M, Ghanaat K, Valizadeh-Dizgikan A, Gohari G, Roadi B, Khonakdar-Tarsi A (2015) The Effect of dexamethasone on expression of inducible nitric oxide synthase gene during liver warm ischemia-reperfusion in rat. Res Molr Med 3:17–22

    Google Scholar 

  11. Mayer J, Giannuzzi LA, Kamino T, Michael J (2007) TEM sample preparation and FIB-induced damage. MRS Bull 32:400–407

    Article  CAS  Google Scholar 

  12. Elias-Miró M, Jiménez-Castro M, Peralta C (2012) Ischemia-reperfusion injury associated with liver transplantation in 2011: Past and future. Liver Transpl Basic 12:21–56

    Google Scholar 

  13. Papadopoulos D, Siempis T, Theodorakou E, Tsoulfas G (2013) Hepatic ischemia and reperfusion injury and trauma: current concepts. Arch Trauma Res 2:63

    Article  Google Scholar 

  14. Jaeschke H (2003) Molecular mechanisms of hepatic ischemia-reperfusion injury and preconditioning. Am J  Physiol-Gastroin Liver Physiol 284:G15–G26

    Article  CAS  Google Scholar 

  15. Nieminen A, Byrne A, Herman B, Lemasters J (1997) Mitochondrial permeability transition in hepatocytes induced by t-BuOOH: NAD (P) H and reactive oxygen species. Am J Physiol-Cell Physiol 272:C1286–C1294

    Article  CAS  Google Scholar 

  16. Babbar M, Sheikh MS (2013) Metabolic stress and disorders related to alterations in mitochondrial fission or fusion. Mol Cell Pharmacol 5:109

    PubMed  PubMed Central  Google Scholar 

  17. Varanita T, Soriano ME, Romanello V, Zaglia T, Quintana-Cabrera R, Semenzato M, Menabo R, Costa V, Civiletto G, Pesce P (2015) The OPA1-dependent mitochondrial cristae remodeling pathway controls atrophic, apoptotic, and ischemic tissue damage. Cell Metabol 21:834–844

    Article  CAS  Google Scholar 

  18. Jaeschke H (1998) Mechanisms of reperfusion injury after warm ischemia of the liver. J Hepato-Biliary-Pancreat Surg 5:402–408

    Article  CAS  Google Scholar 

  19. Katiyar SK (2005) Silymarin and skin cancer prevention: anti-inflammatory, antioxidant and immunomodulatory effects. Int J Oncol 26:169–176

    CAS  PubMed  Google Scholar 

  20. Lingappan K (2018) NF-κB in oxidative stress. Curr Opin Toxicol 7:81–86

    Article  Google Scholar 

  21. Albensi BC (2019) What is nuclear factor kappa B (NF-κB) doing in and to the mitochondrion? Front Cell Dev Biol 7:154

    Article  Google Scholar 

  22. Kim B-R, Seo H-S, Ku J-M, Kim G-J, Jeon CY, Park JH, Jang B-H, Park S-J, Shin Y-C, Ko S-G (2013) Silibinin inhibits the production of pro-inflammatory cytokines through inhibition of NF-κB signaling pathway in HMC-1 human mast cells. Inflamm Res 62:941–950

    Article  CAS  Google Scholar 

  23. Zhang B, Wang B, Cao S, Wang Y, Wu D (2017) Silybin attenuates LPS-induced lung injury in mice by inhibiting NF-κB signaling and NLRP3 activation. Int J Mol Med 39:1111–1118

    Article  CAS  Google Scholar 

  24. Loguercio C, Festi D (2011) Silybin and the liver: from basic research to clinical practice. World J Gastroenterol: WJG 17:2288

    Article  CAS  Google Scholar 

  25. Surai P (2015) Silymarin as a natural antioxidant: an overview of the current evidence and perspectives. Antioxidants 4:204–247

    Article  CAS  Google Scholar 

  26. Arimura S-I, Yamamoto J, Aida GP, Nakazono M, Tsutsumi N (2004) Frequent fusion and fission of plant mitochondria with unequal nucleoid distribution. ProcNat Acad Scis 101:7805–7808

    Article  CAS  Google Scholar 

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Acknowledgements

The authors thank the head and staff of the Immunogenic Research Center (IRC) of Mazandaran University of Medical Sciences who helped us with financial support in conducting the experiments.

Funding

The study was supported by a grant from the Immunogenetic Research Center (IRC) of Mazandaran University of Medical Sciences (Grant Number: 10358).

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Authors and Affiliations

  1. Genetic Biology, Islamic Azad University of Tonekabon, Tonekabon, Iran

    Neda Masoumi Qajari & Abbas Khonakdar-Tarsi

  2. Anatomy and Cell Biology Department, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Mazandaran, Iran

    Majid Malekzadeh Shafaroudi

  3. Department of Biochemistry and Genetics, School of Medicine, Arak University of Medical Sciences, Arak, Iran

    Milad Gholami

  4. Department of Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

    Abbas Khonakdar-Tarsi

  5. Faculty of Medicine, Immunogenetic Research Center (IRC), Mazandaran University of Medical Sciences, Sari, Iran

    Majid Malekzadeh Shafaroudi & Abbas Khonakdar-Tarsi

  6. Department of Medical Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, 17 km Khazarabad road, Sari, Mazandaran, Iran

    Abbas Khonakdar-Tarsi

Authors
  1. Neda Masoumi Qajari
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  2. Majid Malekzadeh Shafaroudi
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Correspondence to Abbas Khonakdar-Tarsi.

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We have no conflicts of interest to declare.

Ethical approval

The protocol of experiments was permitted by the ethical committee of MAZUMS (Code: IR.MAZUMS.REC.1398.10358).

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Qajari, N.M., Shafaroudi, M.M., Gholami, M. et al. Silibinin treatment results in reducing OPA1&MFN1 genes expression in a rat model hepatic ischemia–reperfusion. Mol Biol Rep 47, 3271–3280 (2020). https://doi.org/10.1007/s11033-020-05383-w

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  • DOI: https://doi.org/10.1007/s11033-020-05383-w

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