Investigation of Regeneration Capacity in Rat Liver After Hepatic Resection

Abstract

The liver is the largest gland of the body that secretes both endocrine and exocrine secretions and plays a major role in the regulation of metabolic functions. Numerous factors such as drugs, chemicals, accidents, alcohol, surgical procedures can cause damage to the liver tissue. In this study, we aimed to determine the regeneration capacity of liver tissue in order to recover the mass loss after hepatic resection. In our experiment 21 Wistar albino male rats were used. All experimental groups applied midline incision with laparotomy for resection of liver. At the end of 1 and 7th days, liver tissue removed for light microscopic analysis. The rats were divided three groups: Control, group 1: hepatectomy one day after liver resection, group 2: hepatectomy seven days after liver resection. The tissue of all experimental groups were showed some histopatological changes such as sinuzoidal dilatation, vacuolization in the hepatocytes. These histopathological differentiation was found to be severe in group II compared to other groups. At the end of the 7th day, it was observed that the regeneration increased significantly, and the mitotic index value reached almost the maximum level in the second group. It was observed that the mitotic index value gradually decreased in group I and reached values close to the control group.

Keywords

• Hepatectomy
• Regeneration
• Liver
• Mitosis

Investigation of Regeneration Capacity in Rat Liver After Hepatic Resection

Öz

The liver is the largest gland of the body that secretes both endocrine and exocrine secretions and plays a major role in the regulation of metabolic functions. Numerous factors such as drugs, chemicals, accidents, alcohol, surgical procedures can cause damage to the liver tissue. In this study, we aimed to determine the regeneration capacity of liver tissue in order to recover the mass loss after hepatic resection. In our experiment 21 Wistar albino male rats were used. All experimental groups applied midline incision with laparotomy for resection of liver. At the end of 1 and 7th days, liver tissue removed for light microscopic analysis. The rats were divided three groups: Control, group 1: hepatectomy one day after liver resection, group 2: hepatectomy seven days after liver resection. The tissue of all experimental groups were showed some histopatological changes such as sinuzoidal dilatation, vacuolization in the hepatocytes. These histopathological differentiation was found to be severe in group II compared to other groups. At the end of the 7th day, it was observed that the regeneration increased significantly, and the mitotic index value reached almost the maximum level in the second group. It was observed that the mitotic index value gradually decreased in group I and reached values close to the control group.

Anahtar Kelimeler

• Hepatectomy
• Regeneration
• Liver
• Mitosis

Kaynakça

1. [1] A. Aktümsek, ‘Anatomi ve Fizyoloji İnsan Biyolojisi,’ 3th. Ankara: Nobel Yayınları, 2006, pp.366-7.
2. [2] T.E. Andreoli, ‘Liver,’ In: M.B. Fallon, B.M. McGuire, G.A. Abrams, M.R. Arguedas Eds. Cecil Essentials of Medicine. 5th Ed. Philadelpia, USA: WB Saunders Company, 2001, pp.365-98.
3. [3] R, Adam, P, Bhangui, E. Vibert, D. Azoulay, G. Pelletier, J.C. Duclos-Vallée, D. Samuel, C. Guettier and D. Castaing, ‘Resection or transplantation for early hepatocellular carcinoma in a cirrhotic liver: does size define the best oncological strategy?,’ Ann. Surg. vol. 256, pp. 883-91, Dec, 2012, doi: 10.1097/SLA.0b013e318273bad0.
4. [4] E.A. Pomfret, J.J. Pomposelli, F.D. Gordon, N. Erbay, L. Lyn Price and W.D. Lewis, ‘Liver regeneration and surgical outcome in donors of right-lobe liver grafts,’ Transplantation. vol 76. pp. 5-10, jul, 2003, doi: 10.1097/01.TP.0000079064.08263.8E.
5. [5] Z.G. Ren, J.D. Zhao, K. Gu, J. Wang and G.L. Jiang, ‘Hepatic proliferation after partial liver irradiation in Sprague-Dawley rats,’ Mol. Biol. Rep. Vol. 39, pp. 3829-36, Apr, 2012, doi: 10.1007/s11033-011-1161-z.
6. [6] S. Perek, S. Kapan, Eds. U. Değerli, Y. Bozfakıoğlu, ‘Cerrahi Gastroenteroloji’. 5th ed. İstanbul: Nobel Tıp Kitabevleri, pp. 194-208, 2000.
7. [7] Y. Umeda, H. Iwagaki, M. Ozaki, T. Ogino, T. Iwamoto, R. Yoshida, S. Shinoura, H. Matsuda, H. Sadamori, N. Tanaka and T. Yagi, ‘Refractory response to growth factors impairs liver regeneration after hepatectomy in patients with viral hepatitis,’ Hepatogastroenterology. Vol. 56, pp. 971-7, Jul-Aug, 2009, PMID: 19760923.
8. [8] G.K. Michalopoulos and M.C. DeFrances, ‘Liver regeneration’. Science. Vol. 296, pp. 60-6, 1996.

9. [9] D.R. Labrecque, G. Steele, S. Fogerty, M. Wilson and J. Barton, ‘Purification and physical-chemical characterisation of hepatic stimulator substance,’ Hepatol. Vol. 7, pp. 100-6, 1987.
10. [10] M.J. Xu, D. Feng, H. Wu, H. Wang, Y. Chan, J. Kolls, N. Borregaard, B. Porse, T. Berger, T.W. Mak, J.B. Cowland, X. Kong and B. Gao, ‘Liver is the major source of elevated serum lipocalin-2 levels after bacterial infection or partial hepatectomy: a critical role for IL-6/STAT3,’ Hepatology. Vol. 61, pp. 692-702, Feb; 2015, doi: 10.1002/hep.27447.
11. [11] A. Akcan, C. Kucuk, E. Ok, O. Canoz, S. Muhtaroglu, N. Yilmaz and Z. Yilmaz, ‘The effect of amrinone on liver regeneration in experimental hepatic resection model,’ J. Surg. Res. Vol. 130, pp. 66-72, Jan; 2006, doi: 10.1016/j.jss.2005.07.020.
12. [12] M. Selzne and P.A. Clavien, ‘Failure of regeneration of the steatotic rat liver: Disruption at two different levels in the regeneration pathway,’ Hepatology. Vol. 31, pp. 35-42, 2000.
13. [13] R.G. Kilbourn, D.L. Traber and C. Szabo, ‘Nitrik oxide and shock’. Dis. Mon. Vol. 47, pp. 277-348, 1997.
14. [14] Z. Hou, K. Yanaga, Y. Kamohara, S. Eguchi, R. Tsutsumi and J. Furu, ‘A new suppressive agent against interleukin-1b and tumor necrosis factor-a enhances liver regeneration after partial hepatectomy in rats,’ Hepatology. Research. Vol. 26, pp. 40-46, 2003.
15. [15] N. Fausto, ‘Liver regeneration,’ J. Hepatol. Vol. 32, pp. 19-31, 2000.
16. [16] A.K. Rohlfing, K. Trescher, J. Hähnel, C. Müller and J.P. Hildebrandt, ‘Partial hepatectomy in rats results in immediate down-regulation of p27Kip1 in residual liver tissue by transcriptional and post-translational processes,’ Front. Physiol. Vol. 13, pp. 4-139, Jun, 2013, doi: 10.3389/fphys.2013.00139.
17. [17] R. Veteläinen, A.K. van Vliet and T.M. van, ‘Gulik. Severe steatosis increases hepatocellular injury and impairs liver regeneration in a rat model of partial hepatectomy’ Ann. Surg. vol. 245, pp. 44-50, 2007.
18. [18] D. Palmes and H.U. Spiegel, ‘Animal models of liver regeneration,’ Biomaterials. Vol. 25, pp. 1601-11, 2004.
19. [19] A. Mimuro, T. Aoki, A. Tsuchida, T. Miyashita, Y. Koyanag and S. Enosawa, ‘Effect of ethanolamine on liver regeneration after 90% hepatectomy in rats,’ Transplant. Proc. vol. 234, pp. 2664-7, 2002.
20. [20] T.X. Tang, T. Hashimoto, L.Y. Chao, K. Itoh and T. Manabe, ‘Effects of partial pancreatectomy on liverregeneration in rats’ J. Surg. Res. Vol. 72, pp. 8-14, 1997.
21. [21] E.B. Fernandez, I.A. Sesterhenn, W.F. McCarthy, F.K. Mostofi and J.W. Moul, ‘Proliferating cell nuclear antigen expression to predict occult disease in clinical stage I nonseminomatous testicular germ cell tumors,’ J. Urol. Vol. 152, pp. 1133-8, 1994.
22. [22] N. Ekici, S. Muhtaroğlu, A. Bedirli, ‘Administration of Ginkgo biloba extract (egb761) alone and in combination with fk506 promotes liver regeneration in a rat model of partial hepatectomy,’ Balkan. Med. J. 35(2), pp.174-180, 2018.
23. [23] D. Mangnall, N.C. Bird and A.W. Majeed, ‘The molecular physiology of liver regeneration following partial hepatectomy,’ Liver. Int. Vol. 23, pp. 124-138, 2003.
24. [24] N. Assy and G.Y. Minuk, ‘Liver regeneration: methods for monitoring and their applications,’ J. Hepatol. Vol. 26, pp. 945-52, 1997.
25. [25] D. Mangnall, N.C. Bird and A.W. Majeed, ‘The molecular physiology of liver regeneration following partial hepatectomy,’ Liver. Int. Vol. 23, pp. 124-138, 2003.
26. [26] C. Picard, L. Lambotte, P. Starkel, C. Sempoux, A. Saliez and V.V.D. Berge, ‘Steatosis is not sufficient to cause an impaired regenerative response after partial hepatectomy in rats,’ J. Hepatol. Vol. 32, pp. 645-52, 2002.
27. [27] O. Castro-e-Silva Jr, S. Zucoloto, F.S. Ramalho, L.N.Z. Ramalho and J.M.C. Reis, ‘Antiproliferative Activity of copaifera duckei oleoresin on liver regeneration in rats,’ Phytother. Res. Vol. 18, pp. 92-94, 2004.