Co-administration of prostaglandin E1 with somatostatin attenuates acute liver damage after massive hepatectomy in rats via inhibition of inflammatory responses, apoptosis and endoplasmic reticulum stress

Jia,Changjun; Dai,Chaoliu; Bu,Xianmin; Peng,Songlin; Xu,Feng; Xu,Yongqing; Zhao,Yang

doi:10.3892/ijmm.2012.1213

Co-administration of prostaglandin E1 with somatostatin attenuates acute liver damage after massive hepatectomy in rats via inhibition of inflammatory responses, apoptosis and endoplasmic reticulum stress

Authors:
- Changjun Jia
- Chaoliu Dai
- Xianmin Bu
- Songlin Peng
- Feng Xu
- Yongqing Xu
- Yang Zhao
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Affiliations: Department of Hepato-Biliary-Splenic Surgery, Shengjing Hospital, China Medical University, Shenyang, Liaoning 110004, P.R. China
Published online on: December 14, 2012 https://doi.org/10.3892/ijmm.2012.1213
Pages: 416-422

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Abstract

Acute liver damage is considered to be the major cause of mortality after massive hepatectomy. Prostaglandin E1 (PGE1) and somatostatin (SST) have been shown to protect against hepatic injury of rats after partial hepatectomy. However, the precise mechanisms remain largely unknown. In this study, we examined the effects of PGE1, SST and the combination of these two drugs on acute liver damage of rats after 90% hepatectomy. We found that animal survival was improved when pretreated with PGE1 and SST. Portal venous pressure (PVP), serum alanine aminotransferase (ALT) and aspartate aminotransaminase (AST), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were all reduced after administration of PGE1 and SST. In addition, apoptosis was inhibited via upregulation of Bcl-2 and downregulation of Bax and caspase-3 in drug treatment groups. Furthermore, pretreatment with PGE1 and SST alleviated endoplasmic reticulum (ER) stress by induction of heat shock protein 70 (HSP70) and glucose-regulated protein 78 (GRP78), but suppression of transcription factor C/EBP homologous protein (CHOP). Our data suggest that administration of PGE1 and SST, particularly in combination, may prevent acute liver damage of rats after massive hepatectomy by inhibiting inflammatory responses, apoptosis and ER stress.

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1.	He J, Gu D, Wu X, et al: Major causes of death among men and women in China. N Engl J Med. 353:1124–1134. 2005. View Article : Google Scholar : PubMed/NCBI
2.	Chen JG and Zhang SW: Liver cancer epidemic in China: past, present and future. Semin Cancer Biol. 21:59–69. 2011. View Article : Google Scholar : PubMed/NCBI
3.	Hammond JS, Guha IN, Beckingham IJ and Lobo DN: Prediction, prevention and management of postresection liver failure. Br J Surg. 98:1188–1200. 2011. View Article : Google Scholar : PubMed/NCBI
4.	Jarnagin WR, Gonen M, Fong Y, et al: Improvement in perioperative outcome after hepatic resection: analysis of 1,803 consecutive cases over the past decade. Ann Surg. 236:397–407. 2002. View Article : Google Scholar : PubMed/NCBI
5.	Belghiti J, Hiramatsu K, Benoist S, Massault P, Sauvanet A and Farges O: Seven hundred forty-seven hepatectomies in the 1990s: an update to evaluate the actual risk of liver resection. J Am Coll Surg. 191:38–46. 2000. View Article : Google Scholar : PubMed/NCBI
6.	Virani S, Michaelson JS, Hutter MM, et al: Morbidity and mortality after liver resection: results of the patient safety in surgery study. J Am Coll Surg. 204:1284–1292. 2007. View Article : Google Scholar : PubMed/NCBI
7.	House MG, Ito H, Gonen M, et al: Survival after hepatic resection for metastatic colorectal cancer: trends in outcomes for 1,600 patients during two decades at a single institution. J Am Coll Surg. 210:744–755. 2010. View Article : Google Scholar : PubMed/NCBI
8.	Hasegawa S, Kubota T, Fukuyama N, et al: Apoptosis of hepatocytes is a main cause of inducing lethal hepatic failure after excessive hepatectomy in rats. Transplant Proc. 31:558–559. 1999. View Article : Google Scholar : PubMed/NCBI
9.	Mochida S, Ogata I, Hirata K, Ohta Y, Yamada S and Fujiwara K: Provocation of massive hepatic necrosis by endotoxin after partial hepatectomy in rats. Gastroenterology. 99:771–777. 1990.PubMed/NCBI
10.	Leist M, Gantner F, Bohlinger I, Tiegs G, Germann PG and Wendel A: Tumor necrosis factor-induced hepatocyte apoptosis precedes liver failure in experimental murine shock models. Am J Pathol. 146:1220–1234. 1995.PubMed/NCBI
11.	Andiran F, Ayhan A, Tanyel FC, Abbasoglu O and Sayek I: Regenerative capacities of normal and cirrhotic livers following 70% hepatectomy in rats and the effect of alpha-tocopherol on cirrhotic regeneration. J Surg Res. 89:184–188. 2000.
12.	Kobayashi S, Baba H, Takeno K, et al: Blood flow analysis of compressed nerve root after intravenous injection of lipo-prostaglandin E1. J Orthop Res. 27:1252–1257. 2009. View Article : Google Scholar : PubMed/NCBI
13.	Li JP, Wang Y, Huang YH, Li HP, Chen W and Yang JY: Experimental study of protective mechanism of Lipo-PGE(1) on hepatic ischemia-reperfusion injury. Zhonghua Yi Xue Za Zhi. 89:3371–3374. 2009.(In Chinese).
14.	Matsuo K, Togo S, Sekido H, et al: Pharmacologic preconditioning effects: prostaglandin E1 induces heat-shock proteins immediately after ischemia/reperfusion of the mouse liver. J Gastrointest Surg. 9:758–768. 2005. View Article : Google Scholar
15.	Suehiro T, Shimada M, Kishikawa K, et al: Effect of intraportal infusion to improve small for size graft injury in living donor adult liver transplantation. Transpl Int. 18:923–928. 2005. View Article : Google Scholar : PubMed/NCBI
16.	Ishibe A, Togo S, Kumamoto T, et al: Prostaglandin E1 prevents liver failure after excessive hepatectomy in the rat by upregulating Cyclin C, Cyclin D1, and Bclxl. Wound Repair Regen. 17:62–70. 2009. View Article : Google Scholar : PubMed/NCBI
17.	Ando K, Miyazaki M, Shimizu H, Okuno A and Nakajima N: Beneficial effects of prostaglandin E(1) incorporated in lipid microspheres on liver injury and regeneration after 90% partial hepatectomy in rats. Eur Surg Res. 32:155–161. 2000.PubMed/NCBI
18.	Togo S, Chen H, Takahashi T, et al: Prostaglandin E1 improves survival rate after 95% hepatectomy in rats. J Surg Res. 146:66–72. 2008.PubMed/NCBI
19.	Yoshida N, Iwata H, Yamada T, et al: Improvement of the survival rate after rat massive hepatectomy due to the reduction of apoptosis by caspase inhibitor. J Gastroenterol Hepatol. 22:2015–2021. 2007. View Article : Google Scholar : PubMed/NCBI
20.	Dasgupta P: Somatostatin analogues: multiple roles in cellular proliferation, neoplasia, and angiogenesis. Pharmacol Ther. 102:61–85. 2004. View Article : Google Scholar : PubMed/NCBI
21.	Pinter E, Helyes Z and Szolcsanyi J: Inhibitory effect of somatostatin on inflammation and nociception. Pharmacol Ther. 112:440–456. 2006. View Article : Google Scholar : PubMed/NCBI
22.	Landa I, Arias J, Gomez M, Quadros M, Moreno A and Balibrea JL: Cytoprotective effect of somatostatin in a rat model of hepatic ischemic reperfusion. Hepatology. 16:1474–1476. 1992. View Article : Google Scholar : PubMed/NCBI
23.	Villanueva C and Balanzo J: Variceal bleeding: pharmacological treatment and prophylactic strategies. Drugs. 68:2303–2324. 2008. View Article : Google Scholar : PubMed/NCBI
24.	Pruthi RS, Farouk M, Tsai WH, Michalopoulos G and Meyers WC: The effect of octreotide on hepatic regeneration in rats. Surgery. 113:84–89. 1993.PubMed/NCBI
25.	Yamamoto K, Takenaka K, Matsumata T, Shimada M and Sugimachi K: The effect of octreotide on morphological hepatic regeneration and hepatic functional recovery after a two-thirds hepatectomy in rats. Hepatogastroenterology. 46:1880–1884. 1999.PubMed/NCBI
26.	Hashimoto M, Kothary PC and Raper SE: The effects of transforming growth factor alpha and somatostatin on regenerating hepatocytes in the rat. Regul Pept. 44:49–59. 1993. View Article : Google Scholar : PubMed/NCBI
27.	Feng ZY, Xu X, Wu LJ, Wu J, Zhu SM and Zheng SS: Downregulation of endothelin-1 by somatostatin improves liver function of recipients undergoing adult-to-adult living donor liver transplantation. Chin Med J (Engl). 123:1961–1966. 2010.PubMed/NCBI
28.	Xu X, Man K, Zheng SS, et al: Attenuation of acute phase shear stress by somatostatin improves small-for-size liver graft survival. Liver Transpl. 12:621–627. 2006. View Article : Google Scholar : PubMed/NCBI
29.	Koyama S, Sato Y and Hatakeyama K: The subcutaneous splenic transposition prevents liver injury induced by excessive portal pressure after massive hepatectomy. Hepatogastroenterology. 50:37–42. 2003.
30.	Yachida S, Wakabayashi H, Kokudo Y, et al: Measurement of serum hyaluronate as a predictor of human liver failure after major hepatectomy. World J Surg. 24:359–364. 2000. View Article : Google Scholar : PubMed/NCBI
31.	Panis Y, McMullan DM and Emond JC: Progressive necrosis after hepatectomy and the pathophysiology of liver failure after massive resection. Surgery. 121:142–149. 1997. View Article : Google Scholar : PubMed/NCBI
32.	Ogata T, Yamashita K, Horiuchi H, Okuda K and Todo S: A novel tumor necrosis factor-alpha suppressant, ONO-SM362, prevents liver failure and promotes liver regeneration after extensive hepatectomy. Surgery. 143:545–555. 2008. View Article : Google Scholar
33.	Zinszner H, Kuroda M, Wang X, et al: CHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulum. Genes Dev. 12:982–995. 1998. View Article : Google Scholar : PubMed/NCBI
34.	Garcea G and Maddern GJ: Liver failure after major hepatic resection. J Hepatobiliary Pancreat Surg. 16:145–155. 2009. View Article : Google Scholar : PubMed/NCBI
35.	Nakadaira K, Tsukada K, Sakaguchi T, et al: A pharmacological analysis of prostaglandin E1 on portal blood flow after partial hepatectomy in rats. Surg Today. 23:277–279. 1993. View Article : Google Scholar : PubMed/NCBI
36.	Fausto N and Riehle KJ: Mechanisms of liver regeneration and their clinical implications. J Hepatobiliary Pancreat Surg. 12:181–189. 2005. View Article : Google Scholar : PubMed/NCBI
37.	Selzner N, Selzner M, Odermatt B, Tian Y, Van Rooijen N and Clavien PA: ICAM-1 triggers liver regeneration through leukocyte recruitment and Kupffer cell-dependent release of TNF-alpha/IL-6 in mice. Gastroenterology. 124:692–700. 2003. View Article : Google Scholar : PubMed/NCBI
38.	Cataldegirmen G, Zeng S, Feirt N, et al: RAGE limits regeneration after massive liver injury by coordinated suppression of TNF-alpha and NF-kappaB. J Exp Med. 201:473–484. 2005. View Article : Google Scholar : PubMed/NCBI
39.	Selzner N, Selzner M, Tian Y, Kadry Z and Clavien PA: Cold ischemia decreases liver regeneration after partial liver transplantation in the rat: A TNF-alpha/IL-6-dependent mechanism. Hepatology. 36:812–818. 2002. View Article : Google Scholar : PubMed/NCBI
40.	Morita T, Togo S, Kubota T, et al: Mechanism of postoperative liver failure after excessive hepatectomy investigated using a cDNA microarray. J Hepatobiliary Pancreat Surg. 9:352–359. 2002. View Article : Google Scholar : PubMed/NCBI
41.	Malhi H, Guicciardi ME and Gores GJ: Hepatocyte death: a clear and present danger. Physiol Rev. 90:1165–1194. 2010. View Article : Google Scholar : PubMed/NCBI
42.	Malhi H and Kaufman RJ: Endoplasmic reticulum stress in liver disease. J Hepatol. 54:795–809. 2011. View Article : Google Scholar