[en] [en] BACKGROUND: Curcumin is a pleiotropic antioxidant polyphenol, which has proven to be highly protective in various models of liver injury and inflammation. We hypothesized that adding a stable aqueous curcumin formulation which comprises a water-soluble cyclodextrin curcumin formulation (CDC) complex of the water-insoluble curcumin molecule (Novobion, Espoo, Finland) to preservation solution during liver procurement may reduce ischemia-reperfusion injury and improve graft function after liver transplantation using donation after circulatory death (DCD).
METHODS: In a preclinical pig model of DCD-liver transplantation, livers exposed to 15' of warm ischemia were either modulated (N = 6) with a flush of preservation solution (histidine-tryptophan-ketoglutarate) containing CDC (60 µmol/L) through the vena porta and the aorta, or not (controls, N = 6) before 4 h of cold storage. Area under the curve of log serum aspartate aminotransferase, markers of graft function (lactate, glycemia, prothrombin time, and bile production), inflammation (tumor necrosis factor-alpha), and survival were monitored.
RESULTS: Area under the curve of log serum aspartate aminotransferase were similar between curcumin and control groups (22.12 [20.87-24.88] versus 25.08 [22.1-26.55]; P = 0.28). No difference in the liver function markers were observed between groups except a lower serum lactate level 3-h post-reperfusion in the curcumin group (3 [1.95-6.07] versus 8.2 [4.85-13.45] mmol/L; P = 0.05). Serum tumor necrosis factor-alpha levels were similar in each group. Recipient survival rates were found similar.
CONCLUSIONS: CDC added to the preservation solution in DCD liver pig model did not improve ischemia-reperfusion injury severity, liver function, or survival. Further efforts are needed to explore this strategy, particularly with dynamic preservation, which finds its way into clinical practice.
Disciplines :
Surgery
Author, co-author :
MEURISSE, Nicolas ; Centre Hospitalier Universitaire de Liège - CHU > > Service de chirurgie abdo, sénologique, endocrine et de transplantation ; Laboratory of Abdominal Transplantation, Transplantation Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium ; Department of Abdominal Transplant Surgery, University Hospitals Leuven, Leuven, Belgium
Wylin, Tine; Laboratory of Abdominal Transplantation, Transplantation Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
Heedfeld, Veerle; Laboratory of Abdominal Transplantation, Transplantation Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
Fieuws, Steffen; Laboratory of Abdominal Transplantation, Transplantation Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium ; Department of Abdominal Transplant Surgery, University Hospitals Leuven, Leuven, Belgium ; Interuniversity Institute for Biostatistics and Statistical Bioinformatics, KU Leuven-University of Leuven, Leuven, Belgium
Ceulemans, Laurens; Department of Chronic Diseases and Metabolism, Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium ; Department of Thoracic Surgery, University Hospitals Leuven, Leuven, Belgium
Jochmans, Ina; Laboratory of Abdominal Transplantation, Transplantation Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium ; Department of Abdominal Transplant Surgery, University Hospitals Leuven, Leuven, Belgium
Pirenne, Jacques ; Université de Liège - ULiège > Département des sciences cliniques > Chirurgie abdominale ; Laboratory of Abdominal Transplantation, Transplantation Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium ; Department of Abdominal Transplant Surgery, University Hospitals Leuven, Leuven, Belgium
Monbaliu, Diethard; Laboratory of Abdominal Transplantation, Transplantation Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium ; Department of Abdominal Transplant Surgery, University Hospitals Leuven, Leuven, Belgium
Language :
English
Title :
Effects of Cyclodextrin Curcumin Formulation on Ischemia-Reperfusion Injury in Porcine DCD Liver Transplantation.
Wall S, Plunkett C, Caplan A. A potential solution to the shortage of solid organs for transplantation. JAMA. 2015; 313: 2321-2322.
Briceno J, Marchal T, Padillo J. Influence of marginal donors on liver preservation injury. Transplantation. 2002; 74: 522-526.
Eltzschig H, Eckle T. Ischemia and reperfusion-from mechanism to translation. Nat Med. 2011; 17: 1391-1401.
Zhai Y, Petrowsky H, Hong J. Ischemia-reperfusion injury in liver transplantation-from bench to bedside. Nat Rev Gastroenterol Hepatol. 2013; 10: 79-89.
De Vries Y, von Meijenfeldt FA, Porte RJ. Post-Transplant cholangiopathy: Classification, pathogenesis, and preventive strategies. Biochim Biophys Acta Mol Basis Dis. 2018; 1864: 1507-1515.
Zhai Y, Busuttil RW, Kupiec-Weglinski JW. Liver ischemia and reperfusion injury: New insights into mechanisms of innate-Adaptative immune-mediated tissue inflammation. Am J Transplant. 2011; 11: 2279-2296.
Soares RO, Losada DM, Jordani MC. Ischemia/reperfusion injury revisited: An overview of the latest pharmacological strategies. Int J Mol Sci. 2019; 20: 5034-5079.
Bavarsad K, Riahi MM, Saasat S. Protective effects of curcumin against ischemia-reperfusion injury in the liver. Pharmacol Res. 2019; 141: 53-62.
Rivera-Espinoza Y, Muriel P. Pharmacological actions of curcumin in liver disease or damage. Liver Int. 2009; 29: 1457-1466.
Strimpakos AS, Sharma RA. Curcumin: Preventive and therapeutic properties in laboratory studies and clinical trials. Antioxid Redox Signal. 2008; 10: 511-545.
Shen SQ, Zhang Y, Xiang JJ. Protective effect of curcumin against liver warm ischemia/reperfusion injury in rat model is associated with regulation of heat shock protein and antioxidant enzymes. World J Gastroenterol. 2007; 13: 1953-1961.
Wang L, Li ND, Zang Y. Curcumin protects against hepatic ischemia/reperfusion induced injury through inhibiting TLR4/NF-KB pathway. Oncotarget. 2017; 8: 65414-65420.
Saidi SA, Meurisse N, Jochmans I. Hepatocellular uptake of cyclodextrin-complexed curcumin during liver preservation: A feasibility study. Biopharm Drug Dispos. 2018; 39: 18-29.
Liu Y, Zhang W, Cheng Y. Activation of PPARγ by curcumin protects mice from ischemia/reperfusion injury induced by orthotopic liver transplantation via modulating polarization of Kupffer cells. Int Immunopharmacol. 2018; 62: 270-276.
Prasad S, Tyagi A, Aggarwal B. Recent developments in delivery, bioavailability, absorption and metabolism of curcumin: The golden pigment from golden spice. Cancer Res Treat. 2014; 46: 2-18.
Matloob A, Mourtas S, Klepetsanis P. Increasing the stability of curcumin in serum with liposomes or hybrid drug-in-cyclodextrin-in-liposome systems: A comparative study. Int J Pharm. 2014; 476: 108-115.
Sou K, Inenaga S, Takeoka S. Loading of curcumin into macrophages using lipid-based nanoparticles. Int J Pharm. 2008; 352: 287-293.
Yadav VR, Prasad S, Kannappan R. Cyclodextrin-complexed curcumin exhibits anti-inflammatory and antiproliferative activities superior to those of curcumin through higher cellular uptake. Biochem Pharmacol. 2010; 80: 1021-1032.
Thuillier R, Allain G, Giraud S. Cyclodextrin curcumin formulation improves outcome in a preclinical pig model of marginal kidney transplantation. Am J Transplant. 2014; 14: 1073-1083.
Chen C, Johnston TD, Wu G. Curcumin has potent liver preservation properties in an isolated perfusion model. Transplantation. 2006; 82: 931-937.
Monbaliu D, Crabbe T, Roskams T. Livers from non-heart-beating donors tolerate short periods of warm ischemia. Transplantation. 2005; 79: 1226-1230.
EUR-Lex. Directive 2010/63/EU of the European parliament and of the council of 22 September 2010 on the protection of animals used for scientific purposes. 2010. Available at http://eur-lex.europa.eu/. Accessed September 22, 2022.
Jochmans I, Monbaliu D, Pirenne J. The beginning of an end point: Peak AST in liver transplantation. J Hepatol. 2014; 61: 1186-1187.
Oguz A, Kapan M, Onder A. The effect of curcumin on the liver and remote organs after hepatic ischemia reperfusion injury formed with Pringle manoeuvre in rats. Eur Rev Med Pharmacol Sci. 2013; 17: 457-466.
Ma P, Tumin D, Cismowski M. Effects of preoperative curcumin on the inflammatory response during mechanical circulatory support: A porcine model. Cardiol Res. 2018; 9: 7-10.
Dei Cas M, Ghidoni R. Dietary curcumin: Correlation between bioavailability and health potential. Nutrients. 2019; 11: 2147-2161.
Anand P, Kunnumakkara AB, Newman RA. Bioavailability of curcumin: Problems and promises. Mol Pharm. 2007; 4: 807-818.
Meurisse N, Monbaliu D, Berlakovich G. Heterogeneity of bile duct management in the development of ischemic cholangiopathy after liver transplantation: Results of a European liver and intestine transplant association survey. Transplant Proc. 2019; 51: 1926-1933.
