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The Role of Apelin and Protamine Sulfate in Bile Duct Ligation-Induced Liver Fibrosis in Rats

  • MOLECULAR-BIOLOGICAL PROBLEMS OF DRUG DESIGN AND MECHANISM OF DRUG ACTION
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Pharmaceutical Chemistry Journal Aims and scope

This study was designed to investigate the effectiveness of protamine sulfate as an apelin receptor blocker on cholestatic liver fibrosis persuaded by common bile duct ligation (BDL) in experimental rats and to examine some of the related mechanisms. Three groups of adult male Wistar rats were included: control (sham-operated), BDL, and BDL + protamine sulfate groups. All groups were examined after 4 weeks for serum apelin, total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), hepatic interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA), transforming growth factor-β (TGF-β), and hydroxyproline content, and for extracted[PF1][H2] liver histopathological studies. BDL significantly increased serum apelin, total bilirubin, AST, ALT, ALP, hepatic IL-6, TNF-α, MDA, TGF-β and hydroxyproline content, but it significantly reduced serum albumin level and hepatic GPx and SOD activities. Serum level of apelin significantly revealed positive correlations with TNF-α, MDA, TGF-β, and hydroxyproline content. On the other hand, protamine sulfate significantly attenuated these changes, with no effect on either serum apelin or bilirubin levels, in the treated group. It also improved the hepatic histopathological changes. Protamine sulfate, maybe through its apelin receptor blockade, ameliorated cholestatic liver injury, inflammation, and fibrosis induced by BDL.

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References

  1. A. Ernández-Iglesias and J. Gracia-Sancho, Front. Med., 4, 7 (2017). https://doi.org/10.3389/fmed.2017.00007

    Article  Google Scholar 

  2. L. Russo, J. Gracia-Sancho, H. García-Calderó, et al., Hepatology, 55, 921–930 (2012). https://doi.org/10.1002/hep.24755

    Article  CAS  PubMed  Google Scholar 

  3. B. Li, C. Zhang and Y. T. Zhan, Can. J. Gastroenterol. Hepatol., 2784537 (2018). https://doi.org/10.1155/2018/2784537.

  4. K. Abshagen, M. König, A. Hoppe, et al., Biol., 9(83) (2015). https://doi.org/10.1186/s12918-015-0229-0.

  5. C. R. Bosoi, M. M. Oliveira, R. Ochoa-Sanchez, et al., Metab. Brain Dis., 32, 513 – 518 (2017). https://doi.org/10.1007/s11011-016-9937-4.

    Article  CAS  PubMed  Google Scholar 

  6. J. C. Sαnchez-Salgado, S. Estrada-Soto, S. García-Jiménez, et al., Biomolecules, 9(3), 102 (2019). https://doi.org/10.3390/biom9030102

    Article  CAS  Google Scholar 

  7. H. Samant, W. Manatsathit, D. Dies, et al., World J. Clin. Cases, 7(13), 1571 – 1581 (2019). https://doi.org/10.12998/wjcc.v7.i13.1571

  8. A. O’Carroll, S. Lolait, L. Harris, et al., J. Endocrinol., 219(1), 13 – 35 (2013). https://doi.org/10.1530/JOE-13-0227

    Article  CAS  Google Scholar 

  9. M. Kwon, B. Tuvshintur, W. Kim, et al., J. Sex Med., 10(12), 2928 – 2941 (2013). https://doi.org/10.1111/jsm.12158

    Article  CAS  PubMed  Google Scholar 

  10. P. Melgar-Lesmes, M. Pauta, V. Reichenbach, et al., Gut, 60, 1404 – 1411 (2011). https://doi.org/10.1136/gut.2010.234690

    Article  CAS  PubMed  Google Scholar 

  11. A. Principe, P. Melgar-Lesmes, G. Fernαndez-Varo, et al., Hepatology, 48, 1193 – 1201 (2008). https://doi.org/10.1002/hep.22467

    Article  CAS  PubMed  Google Scholar 

  12. W. Chen, T. Oue, T. Ueno, et al., Pediatr. Surg. Int., 29, 79 – 85 (2013). https://doi.org/10.1007/s00383-012-3210-7

    Article  PubMed  Google Scholar 

  13. S. Y. Lv, B. Cui, W. D, Chen, et al., Oncotarget, 8(67), 112145 – 112151 (2017). https://doi.org/10.18632/oncotarget.22841

  14. V. Reichenbach, J. Ros, G. Fernández-Varo, et al., J. Pharmacol. Exp. Ther., 340, 629 – 37 (2012). https://doi.org/10.1124/jpet.111.188078

    Article  CAS  PubMed  Google Scholar 

  15. D. K. Lee, V. R. Saldivia, T. Nguyen, et al., Endocrinology, 146(1), 231 – 236 (2005). https://doi.org/10.1210/en.2004-0359

    Article  CAS  PubMed  Google Scholar 

  16. S. Le Gonidec, C. Chaves-Almagro, Y. Bai, et al., FASEB J., 31(6), 2507–2519 (2017). https://doi.org/10.1096/fj.201601074R

    Article  PubMed  PubMed Central  Google Scholar 

  17. K. X. Liuhttps://www.ncbi.nlm.nih.gov/pubmed/–term=Liu%20KX%5BAuthor%5D&cauthor=true&cauthoruid=9458769, Y Katohttps://www.ncbi.nlm.nih.gov/pubmed/-term=Kato%20Y%5BAuthor%5D&cauthor=true&cauthoruid=9458769, T. I. Kaku, et al., Pharmaceut. Res., 26(4), 1012 – 1021 (2009). https://doi.org/10.1007/s11095-008-9810-1.

  18. Y. X. Zhou, Y. Ni, Y. B. Liu, et al., Exp. Ther. Med., 8(1), 15 – 20 (2014). https://doi.org/10.3892/etm.2014.1697

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. F. Liu, L. Chen, H. Y. Rao, et al., J. Tech. Meth. and Pathol., 97(1), 84 – 92 (2017). https://doi.org/10.1038/labinvest.2016.128.

    Article  CAS  Google Scholar 

  20. A. Slododa, J. Birnpaum, A. Oronsky, et al., Arthritis Rheum., 24, 616 – 624 (1981). https://doi.org/10.1002/art.1780240408

    Article  Google Scholar 

  21. J. S. Rec, J. Clin. Biochem., 8, 658 (1970).

    Google Scholar 

  22. A. Belfield and D. M. Goldberg, Biochem. Med,. 4, 135–148 (1971). https://doi.org/10.1016/0006-2944(70)90090-6.

    Article  Google Scholar 

  23. M. A. Stoskopf, Sounders Company. U.S.A., 882 (1993).

  24. M. I. Walters and H. W. Gerarde, Michrochem. J., 15, 231 – 243 (1970). https://doi.org/10.1016/0026-265X(70)90045-7

    Article  CAS  Google Scholar 

  25. O. Firat, O. Makayhttps://www.ncbi.nlm.nih.gov/pubmed/-term=Makay%20O%5BAuthor%5D&cauthor=true&cauthoruid=28706885, L. Yeniayhttps://www.ncbi.nlm.nih.gov/pubmed/-term=Yeniay%20L%5BAuthor%5D&cauthor=true&cauthoruid=28706885, et al., Ann. Surg. Treat. Res., 93(1), 1 – 10 (2017). https://doi.org/10.4174/astr.2017.93.1.1

  26. E. Engvall and P. Perlmann, Immunochemistry, 8(9), 871 – 874 (1971). https://doi.org/10.1016/0019-2791(71)90454-x

    Article  CAS  PubMed  Google Scholar 

  27. B. Fernando, R. Marley, S. Holt, et al., Hepatology, 28(3), 689 (1998). https://doi.org/10.1002/hep.510280314

    Article  CAS  PubMed  Google Scholar 

  28. D. Gerard-Monnier, I. Erdelmeier, K. Regnard, et al., Chem. Res. Toxicol., 11, 1176 – 1183 (1998). https://doi.org/10.1021/tx9701790

    Article  CAS  PubMed  Google Scholar 

  29. C. Nebot, M. Moutet, P. Huet, et al., Anal. Biochem., 214, 442 – 451 (1993). https://doi.org/10.1006/abio.1993.1521

    Article  CAS  PubMed  Google Scholar 

  30. F. Ursini, M. Maiorino, M. Valente, et al., Biochim. Biophys. Acta, 710, 197 – 211 (1982). https://doi.org/10.1016/0005-2760(82)90150-3

    Article  CAS  PubMed  Google Scholar 

  31. I. S. Jamal, V. N. Finelli & S. Q. Hee, Anal. Biochem., 112(1), 70 – 75 (1981). https://doi.org/10.1016/0003-2697(81)90261-x.

    Article  Google Scholar 

  32. Z. Altunkaynak, Eur. J. Gen. Med., 2(3), 100 – 109 (2005). https://doi.org/10.29333/ejgm/82319.

  33. A. E. Alsemeh, R. S. Moawad & E. R. Abdelfattah, Anatom. Sci. Int., 94(4), 307 – 323 (2019). https://doi.org/10.1007/s12565-019-00488-0.

    Article  Google Scholar 

  34. C. Jüngst and F. Lammert, Dig. Dis., 31, 152–154 (2013). https://doi.org/10.1159/000347210

    Article  PubMed  Google Scholar 

  35. Y. Lim, E. Choi, Y. Jang, et al., Gut Liver, 10(1), 109 – 116 (2016). https://doi.org/10.5009/gnl14345

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. N. E. Owen, D. Nyimanu, R. E. Kuc, et al., Peptides, 136, 170440 (2020). https://doi.org/10.1016/j.peptides.2020.170440

    Article  CAS  PubMed  Google Scholar 

  37. C. Teixeira, E. Franco, P. A. Oliveira, et al., In Vivo, 27(5), 635 – 40 (2013). https://doi.org/10.1177/0960327112474832.

    Article  CAS  PubMed  Google Scholar 

  38. H. G. Kim, J. M. Han, J. S. Leehttps://www.ncbi.nlm.nih.gov/pubmed/-term=Lee%20JS%5BAuthor%5D&cauthor=true&cauthoruid=26412144, et al., Sci. Rep., 28(5), 14531 (2015). https://doi.org/10.1038/srep14531.

  39. T. Tsuchida and S. L. Friedman, Nat. Rev. Gastroenterol. Hepatol., 14, 397 – 411 (2017). https://doi.org/10.1038/nrgastro.2017.38

    Article  CAS  PubMed  Google Scholar 

  40. L. Cordero-Espinoza and M. Huch, J. Clin. Investig., 128, 85 – 96 (2018). https://doi.org/10.1172/JCI93562

    Article  PubMed  PubMed Central  Google Scholar 

  41. G. Tahan, O. Tarcin, V. Tahan, et al., Dig. Dis. Sci., 52, 3348 – 3354 (2007). https://doi.org/10.1007/s10620-006-9717-9

    Article  CAS  PubMed  Google Scholar 

  42. G. Datta, B. J. Fuller & B. R. Davidson, World J. Gastroenterol., 19(11), 1683 – 1698 (2013). https://doi.org/10.3748/wjg.v19.i11.1683

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. D. García-Díaz, J. Campión, F. I. Milagro, et al., Mol. Cell Biochem., 305, 87–94 (2007). https://doi.org/10.1007/s11010-007-9531-5.

    Article  CAS  PubMed  Google Scholar 

  44. Y. Lu, X. Zhu, G. X. Liang, et al., Amino Acids, 43, 2125 – 2136 (2012). https://doi.org/10.1007/s00726-012-1298-7

    Article  CAS  PubMed  Google Scholar 

  45. D. Lv, H. Li & L. Chen, Acta Biochim. Biophys. Sin. (Shanghai), 45, 527 – 533 (2013). https://doi.org/10.1093/abbs/gmt040

    Article  CAS  PubMed  Google Scholar 

  46. A. Than, X. Zhang, M. K. Leow, et al., J. Biol. Chem., 289, 3763 – 3774 (2014). https://doi.org/10.1074/jbc.M113.526210

    Article  CAS  PubMed  Google Scholar 

  47. C. Foussal, O. Lairez, D. Calise, et al., FEBS Lett., 584, 2363 – 2370 (2010). https://doi.org/10.1016/j.febslet.2010.04.025

    Article  CAS  PubMed  Google Scholar 

  48. T. Sagiroglu, M. B. Aksoy, G. Sagiroglu, et al., Indian J. Surg., 76(2), 111 – 116 (2014). https://doi.org/10.1007/s12262-012-0676-4

    Article  Google Scholar 

  49. Q. Zhou, J. Cao and L. Chen, Int. J. Mo.l Med., 37(5), 1159 – 1169 (2016). https://doi.org/10.3892/ijmm.2016.2544

  50. T. Kisseleva and D. A. Brenner, J. Gastroenterol. Hepatol., 22(1), S73–S78 (2007). https://doi.org/10.1111/j.1440-1746.2006.04584.x

    Article  CAS  PubMed  Google Scholar 

  51. C. Erenoğlu, M. Kanter, B. Aksu, et al., Balkan Med. J., 28, 352 – 357 (2011). https://doi.org/10.5174/tutfd.2010.04312.1

    Article  CAS  Google Scholar 

  52. S. A. Gabr, A. H. Alghadir, Y. E. Sherif, et al., Biomarkers in Liver Disease, 1 – 21 (2017). https://doi.org/10.1007/978-94-007-7675-326

  53. G. Svegliati-Baroni, S. De Minicis and M. Marzioni, Liver Int., 28, 1052–1064 (2008). https://doi.org/10.1111/j.1478-3231.2008.01825.x

    Article  CAS  PubMed  Google Scholar 

  54. E. Marei, H. Mohamed & D. Shaheen, J. Radiation Res. & Appl. Sci., 13, 155 – 163 (2020). https://doi.org/10.1080/16878507.2020.1715556

    Article  CAS  Google Scholar 

  55. H. Z. Ying, Q. Chen, W. Y. Zhang, et al., Mol. Med. Rep., 16, 7879 – 7889 (2017). https://doi.org/10.3892/mmr.2017.7641

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Y. Wang, J. Song, H. Bian, et al., Mol. Cell Biochem., 460, 205 – 215 (2019). https://doi.org/10.1007/s11010-019-03581-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Physiology Department, Faculty of Medicine-Zagazig University, Zagazig, Egypt

    Suzan M. M. Moursi & Sherein F. El-sayed

  2. Zoology Department, Faculty of Science-Zagazig University, Zagazig, Egypt

    Eman El Bahaie

  3. Clinical pharmacology Department, Faculty of Medicine-Zagazig University, Zagazig, Egypt

    Amira Mohamed Abdelhamid

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  2. Eman El Bahaie
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  3. Amira Mohamed Abdelhamid
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  4. Sherein F. El-sayed
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Correspondence to Amira Mohamed Abdelhamid.

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Moursi, S.M.M., Bahaie, E.E., Abdelhamid, A.M. et al. The Role of Apelin and Protamine Sulfate in Bile Duct Ligation-Induced Liver Fibrosis in Rats. Pharm Chem J 57, 1339–1349 (2023). https://doi.org/10.1007/s11094-023-02995-x

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