The preventive effect of sulforaphane on liver injury in a non-heart-beating donor model

Aim: In this preliminary study, we aimed to investigate the effect of sulforaphane (SFN) warm ischemia in a non-heart beat rat liver model (NHBD). Materials and Methods: Livers taken from NHBD 15,30,60 min after warm ischemia were stored up at University of Wisconsin solution for 5 h at 40C [cold storage (CS)] and were, then, exposed to 2 h of machine reperfusion (MRP) at 370C. In the study group, SFN 5 mg/kg was intraperitoneal given 30 min before the introduction of NHB. Firstly, we divided the rats into the control and SFN groups. Then, each group was divided into three groups (n=10 in each) including control I, II, III and SFN I, II, III groups (15-, 30-, and 60-min warm ischemia period, respectively).Control and study groups at the same time of ischemia were compared with each other in terms of lactate, AST, ALT, IL-6, TNF-α and morphologically.Results: In the group treated with SFN, AST, ALT, TNF-α, IL-6, and lactate levels were lower, compared to the control group. Histopathologically, Bcl-2 staining intensity and percentages of staining were statistically significant, compared to the control and study groups during 15-min warm ischemia. Although not statistically significant, the intensity and percentage of staining were higher at 30 min and identical at 60 min. Conclusion: Our study results suggest that, despite prolonged warm ischemia time, SFN can biochemically and morphologically protect the liver from the hazardous effects of ischemia reperfusion in an experimentally-controlled NHB in rats, indicating an increased utilization rate of NHBDs.

PDF

___

1. XianwaNiu, Wen Hua Huang, Bastiaan De Boer, et al.Iron-Induced Oxidative Rat Liver Injury After Non– Heart-Beating Warm Ischemia Is Mediatedby Tumor Necrosis Factor a and Prevented byDeferoxamin. LiverTranplatation 2014;20:904-11.
2. Guerrero-Beltrán CE, Calderón-Oliver M, Pedraza- ChaverriJ,et al. Protective effect of sulforaphane against oxidative stress: recentadvances. ExpToxicolPathol 2012; 64: 503-8.
3. Okada K, Warabi E, SugimotoH, et al. Nrf2 inhibits hepatic iron accumulation and counteracts oxidative stress-induced liver injury in nutritional steatohepatitis. J Gastroenterol 2012;47:924-35.
4. Seung-HaeBaek, Min Park, Jae-Hee Suh, et al. Protective effects of an extract of young radish (Raphanussativus L) cultivated with sulfur (sulfurradish extract) and of sulforaphane on carbon tetrachloride-induced hepatotoxicity. Biosci Biotechnol Biochem, 2008;72:1176-82.
5. Sue Kyung Yu, Gaab Soo Kim, Jun Young Chung. Anesthesia for liver transplantation from a maastricht category 4 non-heart-beating donor -A case report-. Korean Journal of Anesthsiology 2010;59:119-23.
6. Olivier de Rougemont, KunoLehmann, Pierre-Alain Clavien.Preconditioning, organ preservation, and postconditioning to prevent ischemia-reperfusion injury to the liver. Liver Transplantation 2009;15:1172- 82.
7. A Yalin, S Arbak, F Ercan. Preservatıon of lıver wıth euro-collıns solutıon: evaluatıon of ultrastructural alteratıons.MarmaraMedikal J 1999;12:29-32.
8. Karlsson JO. Cryopreservation; freezing and vitrifi cation. Science 2002;296:655-6.
9. JM Neuberger, WO Bechstein, DRJ Kuypers, et all. Practical Recommendations for Long-term Management of Modifiable Risks in Kidney and Liver Transplant Recipients. Transplantation 2017;101:1- 56.
10. JM O'Callaghan, RD Morgan, SR Knight, et al. Systematic review and meta-analysis of hypothermic machine perfusion versus static cold storage of kidney allografts on transplant outcomes.BJS 2013;100: 991-1001.
11. Belzer F, Ashby B, Dunphy J. 24-hour and 72-hour preservation of canine kidneys. Lancet 1967;2:536-8.
12. Karlsson JO. Cryopreservation; freezing and vitrifi cation. Science 2002;296:655-6.
13. Hai-Dong Zhao, Feng Zhang, Gang Shen, et. al, Sulforaphane protects liver injury induced by intestinal ischemia reperfusion through Nrf2-ARE pathway World J Gastroenterol 2010;16: 3002-10.
14. Reddy S, Zilvetti M, BrockmannJ, et al. Liver transplantation from non–heart–beating donors: current status and future prospects. Liver Transpl 2004;10:1223-32.
15. Fondevila C, Busuttil RW, Kupiec-Weglinski JW et al. Hepatic ischemia/reperfusion injury–a fresh look. ExpMolPathol 2003;74:86-93.
16. Dokumacioglu E, Iskender H, Aktas MS, et al.The effect of sulforaphane on oxidative stress and inflammationin rats with toxic hepatitis induced by acetaminophene.Bratislava Med J 2017;118:453 -9.
17. Li W, Chan AC, Lau YJ, et al. Superoxide and nitric oxide production by Kupffer cells in rats with obstructive jaundice: Effect of internal and external drainage. J GastroenterolHepatol 2004;19:160-5.
18. Rudiger HA, Clavien PA. Tumor necrosis factor alpha, but not Fas, mediates hepatocellular apoptosis in the murine ischemic liver. Gastroenterology 2002;122: 202-10.
19. Kong JS, Yoo SA, Kim HS, et al. Inhibition of synovial hyperplasia, rheumatoid T cell activation, and experimental arthritis in mice by sulforaphane, a naturally occurring isothiocyanate. Arthritis Rheum2010;62:159-70.
20. Chattopadhyay P, Chaudhury P ,Wahi K. Bcl-2 Expression Alters the Mitochondrial Tri Carboxyl Acid Pathway in Hepatic Ischemic and ReperfusionInduced Necrosis and Apoptosis in Rat Liver. Indian J Pharm Sci 2010;72:437-41.
21. Gapany C, Zhao M, Zimmermann A, et al. The apoptosis protector, bcl-2 protein, is downregulated in bile duct epithelial cells of human liver allografts. Hepatology1997;26:535-42.
22. Cetin M, Yİlmaz Z, ArtisT, et al.The Effect of Edavaron's Liver Damage in an Experimental Non-Heart Beating Donor Model. Erciyes Med J 2012;34:127-31.