The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
권호 표지
DOI QR코드

DOI QR Code

Loss of RAR-α and RXR-α and enhanced caspase-3-dependent apoptosis in N-acetyl-p-aminophenol-induced liver injury in mice is tissue factor dependent

  • Abdel-Bakky, Mohamed Sadek (Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University) ;
  • Helal, Gouda Kamel (Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University) ;
  • El-Sayed, El-Sayed Mohamed (Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University) ;
  • Amin, Elham (Department of Pharmacognosy, Faculty of Pharmacy, Beni-Suef University) ;
  • Alqasoumi, Abdulmajeed (Department of Pharmacy Practice, College of Pharmacy, Qassim University) ;
  • Alhowail, Ahmad (Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University) ;
  • Abdelmoti, Eman Sayed Said (Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University) ;
  • Saad, Ahmed Saad (Department of Pharmacology and Toxicology, Faculty of Pharmacy, Port Said University)
  • Received : 2020.09.21
  • Accepted : 2021.02.26
  • Published : 2021.09.01
Download PDF
⟨ Previous Next ⟩

Abstract

Tissue factor (TF) activates the coagulation system and has an important role in the pathogenesis of various diseases. Our previous study stated that retinoid receptors (RAR-α and RXR-α) are released as a lipid droplet in monocrotaline/lipopolysaccharide-induced idiosyncratic liver toxicity in mice. Herein, the interdependence between the release of retinoid receptors RAR-α and RXR-α and TF in N-acetyl-p-aminophenol (APAP)-induced mice liver toxicity, is investigated. Serum alanine transaminase (ALT) level, platelet and white blood cells (WBCs) counts, protein expression of fibrin, TF, cyclin D1 and cleaved caspase-3 in liver tissues are analyzed. In addition, histopathological evaluation and survival study are also performed. The results indicate that using of TF-antisense (TF-AS) deoxyoligonucleotide (ODN) injection (6 mg/kg), to block TF protein synthesis, significantly restores the elevated level of ALT and WBCs and corrects thrombocytopenia in mice injected with APAP. TF-AS prevents the peri-central overexpression of liver TF, fibrin, cyclin D1 and cleaved caspase-3. The release of RXR-α and RAR-α droplets, in APAP treated sections, is inhibited upon treatment with TF-AS. In conclusion, the above findings designate that the released RXR-α and RAR-α in APAP liver toxicity is TF dependent. Additionally, the enhancement of cyclin D1 to caspase-3-dependent apoptosis can be prevented by blocking of TF protein synthesis.

Keywords

Acknowledgement

The authors would like to thank all members of Pharmacology department, faculty of Pharmacy, Al-Azhar University for all supports during proceeding of research. Researchers would like to thank the Deanship of Scientific Research, Qassim University for funding publication of this project.

References

  1. Heestermans M, Salloum-Asfar S, Streef T, Laghmani EH, Salvatori D, Luken BM, Zeerleder SS, Spronk HMH, Korporaal SJ, Kirchhofer D, Wagenaar GTM, Versteeg HH, Reitsma PH, Renne T, van Vlijmen BJM. Mouse venous thrombosis upon silencing of anticoagulants depends on tissue factor and platelets, not FXII or neutrophils. Blood. 2019;133:2090-2099. https://doi.org/10.1182/blood-2018-06-853762
  2. Arai M, Mochida S, Ohno A, Ogata I, Obama H, Maruyama I, Fujiwara K. Blood coagulation equilibrium in rat liver microcirculation as evaluated by endothelial cell thrombomodulin and macrophage tissue factor. Thromb Res. 1995;80:113-123. https://doi.org/10.1016/0049-3848(95)00157-M
  3. Bataller R, Gabele E, Parsons CJ, Morris T, Yang L, Schoonhoven R, Brenner DA, Rippe RA. Systemic infusion of angiotensin II exacerbates liver fibrosis in bile duct-ligated rats. Hepatology. 2005;41:1046-1055. https://doi.org/10.1002/hep.20665
  4. Copple BL, Woolley B, Banes A, Ganey PE, Roth RA. Anticoagulants prevent monocrotaline-induced hepatic parenchymal cell injury but not endothelial cell injury in the rat. Toxicol Appl Pharmacol. 2002;180:186-196. https://doi.org/10.1006/taap.2002.9394
  5. Pearson JM, Schultze AE, Schwartz KA, Scott MA, Davis JM, Roth RA. The thrombin inhibitor, hirudin, attenuates lipopolysaccharide-induced liver injury in the rat. J Pharmacol Exp Ther. 1996;278:378-383.
  6. Goodman DS. Vitamin A and retinoids in health and disease. N Engl J Med. 1984;310:1023-1031. https://doi.org/10.1056/NEJM198404193101605
  7. Nakamura K, Kadotani Y, Ushigome H, Akioka K, Okamoto M, Ohmori Y, Yaoi T, Fushiki S, Yoshimura R, Yoshimura N. Antisense oligonucleotide for tissue factor inhibits hepatic ischemic reperfusion injury. Biochem Biophys Res Commun. 2002;297:433-441. https://doi.org/10.1016/S0006-291X(02)02024-7
  8. Hammad MA, Abdel-Bakky MS, Walker LA, Ashfaq MK. Oxidized low-density lipoprotein and tissue factor are involved in monocrotaline/lipopolysaccharide-induced hepatotoxicity. Arch Toxicol. 2011;85:1079-1089. https://doi.org/10.1007/s00204-011-0649-6
  9. Pohl E, Tomlinson CWE. Classical pathways of gene regulation by retinoids. Methods Enzymol. 2020;637:151-173. https://doi.org/10.1016/bs.mie.2020.03.008
  10. Ohata M, Lin M, Satre M, Tsukamoto H. Diminished retinoic acid signaling in hepatic stellate cells in cholestatic liver fibrosis. Am J Physiol. 1997;272(3 Pt 1):G589-G596.
  11. Nagpal S, Chandraratna RA. Recent developments in receptor-selective retinoids. Curr Pharm Des. 2000;6:919-931. https://doi.org/10.2174/1381612003400146
  12. Mezaki Y, Yamaguchi N, Yoshikawa K, Miura M, Imai K, Itoh H, Senoo H. Insoluble, speckled cytosolic distribution of retinoic acid receptor alpha protein as a marker of hepatic stellate cell activation in vitro. J Histochem Cytochem. 2009;57:687-699. https://doi.org/10.1369/jhc.2009.953208
  13. Abdel-Bakky MS, Hammad MA, Walker LA, Ashfaq MK. Tissue factor dependent liver injury causes release of retinoid receptors (RXR-α and RAR-α) as lipid droplets. Biochem Biophys Res Commun. 2011;410:146-151. https://doi.org/10.1016/j.bbrc.2011.05.127
  14. Abdel-Bakky MS, Helal GK, El-Sayed EM, Alhowail AH, Mansour AM, Alharbi KS, Amin E, Allam S, Salama SA, Saad AS. Silencing of tissue factor by antisense deoxyoligonucleotide mitigates thioacetamide-induced liver injury. Naunyn Schmiedebergs Arch Pharmacol. 2020;393:1887-1898. https://doi.org/10.1007/s00210-020-01896-0
  15. Hammad MA, Abdel-Bakky MS, Walker LA, Ashfaq MK. Tissue factor antisense deoxyoligonucleotide prevents monocrotaline/LPS hepatotoxicity in mice. J Appl Toxicol. 2013;33:774-783. https://doi.org/10.1002/jat.2728
  16. Gardner CR, Laskin JD, Dambach DM, Sacco M, Durham SK, Bruno MK, Cohen SD, Gordon MK, Gerecke DR, Zhou P, Laskin DL. Reduced hepatotoxicity of acetaminophen in mice lacking inducible nitric oxide synthase: potential role of tumor necrosis factor-alpha and interleukin-10. Toxicol Appl Pharmacol. 2002;184:27-36. https://doi.org/10.1006/taap.2002.9474
  17. James LP, Mayeux PR, Hinson JA. Acetaminophen-induced hepatotoxicity. Drug Metab Dispos. 2003;31:1499-1506. https://doi.org/10.1124/dmd.31.12.1499
  18. Dragomir AC, Laskin JD, Laskin DL. Macrophage activation by factors released from acetaminophen-injured hepatocytes: potential role of HMGB1. Toxicol Appl Pharmacol. 2011;253:170-177. https://doi.org/10.1016/j.taap.2011.04.003
  19. Liu ZX, Han D, Gunawan B, Kaplowitz N. Neutrophil depletion protects against murine acetaminophen hepatotoxicity. Hepatology. 2006;43:1220-1230. https://doi.org/10.1002/hep.21175
  20. Ganey PE, Luyendyk JP, Newport SW, Eagle TM, Maddox JF, Mackman N, Roth RA. Role of the coagulation system in acetaminophen-induced hepatotoxicity in mice. Hepatology. 2007;46:1177-1186. https://doi.org/10.1002/hep.21779
  21. Brass LF, Zhu L, Stalker TJ. Novel therapeutic targets at the platelet vascular interface. Arterioscler Thromb Vasc Biol. 2008;28:s43-s50.
  22. Mackman N. Tissue-specific hemostasis in mice. Arterioscler Thromb Vasc Biol. 2005;25:2273-2281. https://doi.org/10.1161/01.ATV.0000183884.06371.52
  23. Friedman A, Halevy O, Schrift M, Arazi Y, Sklan D. Retinoic acid promotes proliferation and induces expression of retinoic acid receptor-alpha gene in murine T lymphocytes. Cell Immunol. 1993;152:240-248. https://doi.org/10.1006/cimm.1993.1284
  24. Okuno M, Sato T, Kitamoto T, Imai S, Kawada N, Suzuki Y, Yoshimura H, Moriwaki H, Onuki K, Masushige S, Muto Y, Friedman SL, Kato S, Kojima S. Increased 9,13-di-cis-retinoic acid in rat hepatic fibrosis: implication for a potential link between retinoid loss and TGF-beta mediated fibrogenesis in vivo. J Hepatol. 1999;30:1073-1080. https://doi.org/10.1016/S0168-8278(99)80262-1
  25. Chen Q, Yan D, Zhang Q, Zhang G, Xia M, Li J, Zhan W, Shen E, Li Z, Lin L, Chen YH, Wan X. Treatment of acetaminophen-induced liver failure by blocking the death checkpoint protein TRAIL. Biochim Biophys Acta Mol Basis Dis. 2020;1866:165583. https://doi.org/10.1016/j.bbadis.2019.165583
  26. Guo Q, Shen Z, Yu H, Lu G, Yu Y, Liu X, Zheng P. Carnosic acid protects against acetaminophen-induced hepatotoxicity by potentiating Nrf2-mediated antioxidant capacity in mice. Korean J Physiol Pharmacol. 2016;20:15-23. https://doi.org/10.4196/kjpp.2016.20.1.15
  27. Wu YL, Jiang YZ, Jin XJ, Lian LH, Piao JY, Wan Y, Jin HR, Joon Lee J, Nan JX. Acanthoic acid, a diterpene in Acanthopanax koreanum, protects acetaminophen-induced hepatic toxicity in mice. Phytomedicine. 2010;17:475-479. https://doi.org/10.1016/j.phymed.2009.07.011
  28. Helal MG, Samra YA. Irbesartan mitigates acute liver injury, oxidative stress, and apoptosis induced by acetaminophen in mice. J Biochem Mol Toxicol. 2020;34:e22447. https://doi.org/10.1002/jbt.22447
  29. Li J, Li X, Xu W, Wang S, Hu Z, Zhang Q, Deng X, Wang J, Zhang J, Guo C. Antifibrotic effects of luteolin on hepatic stellate cells and liver fibrosis by targeting AKT/mTOR/p70S6K and TGFβ/Smad signalling pathways. Liver Int. 2015;35:1222-1233. https://doi.org/10.1111/liv.12638
  30. Bhushan B, Walesky C, Manley M, Gallagher T, Borude P, Edwards G, Monga SP, Apte U. Pro-regenerative signaling after acetaminophen-induced acute liver injury in mice identified using a novel incremental dose model. Am J Pathol. 2014;184:3013-3025. https://doi.org/10.1016/j.ajpath.2014.07.019
  31. Bustany S, Cahu J, Guardiola P, Sola B. Cyclin D1 sensitizes myeloma cells to endoplasmic reticulum stress-mediated apoptosis by activating the unfolded protein response pathway. BMC Cancer. 2015;15:262. https://doi.org/10.1186/s12885-015-1240-y