Obesity, lipid profiles and oxidative stress in children after liver transplantation
Abstract
PURPOSE: Liver transplant recipients are potentially at higher risk cardiovascular complications mostly due to immunosuppressive treatment. The aim of the study was to assess lipid profiles and oxidative stress markers after pediatric liver transplantation in long-term stable recipients.
METHOD: In 74 children at least 3 years after LTx with normal graft function, we assessed lipid parameters, insulin resistance, markers of oxidative stress and atherosclerosis: glutathione (GSH), glutathione peroxidase (GPx), asymmetrical dimethyl arginine (ADMA) and oxidized low-density lipoprotein (oxyLDL). All patients were assessed after 3-year follow-up. Baseline results were compared with healthy age-matched control group.
RESULTS: Transplant recipients presented with normal lipid profiles but there were differences in ADMA 0,84 ± 0,31 vs. 0,29 ± 0,17 mol/l , p<0.001, GSH 689.5 ± 66.2 vs 782.4 ± 17.2 mol/ml p<0.001, GPx 30,4 ± 3,0 vs 32,6 ± 1,6 U/gHb p<0.001 and oxyLDL 316.4 ± 118.3 vs 124.6 ± 20.4 mU/ml, p<0,0001. Insulin resistance by HOMA-IR was increased in study group. After 3,1 ± 0,3 years follow-up we found significant decrease of oxidative stress markers in the study group.
CONCLUSION: Children after LTx present with normal lipid profiles but are at higher risk of oxidative stress.
References
Buculvas J. Long-term outcomes in pediatric liver transplantation. Liver transplant 2009;15:S6-S11,. http://doi.org/10.1002/lt.21915.
Christians U, Gottschalk S, Miljus J, et al. Alterations in glucose metabolism by cyclosporine in rat brain slices link to oxidative stress: interactions with mTOR inhibitors. Br J Pharmacol 2004;143:388-96, http://doi.org/10.1038/sj.bjp.0705939
D'Avola D, Cuervas-Mons V, Martí J, Ortiz de Urbina J, Lladó L, Jimenez C, Otero E, Suarez F, Rodrigo JM, Gómez MA, Fraga E, Lopez P, Serrano MT, Rios A, Fábrega E, Herrero JI. Cardiovascular morbidity and mortality after liver transplantation: The protective role of mycophenolate mofetil. Liver Transpl. 2017;23(4):498-509; http://doi.org/10.1002/lt.24738
Granot E, Elinav H, Kohen R. Markers of Oxidative Stress in Cyclosporine-Treated and Tacrolimus-Treated Children After Liver Transplantation. Liver Transpl 2002; 8:469-75 http://doi.org/1 0.1053/jlts.2002.32716
Hannson GK. Inflammation, Atherosclerosis and Coronary Artery Disease. N Engl J Med 2005;352:1685-95 http://doi.org/ 10.1056/NEJMra043430
Krötz F, Keller M, Derflinger S, et al. Mycophenolate Acid Inhibits Endothlial NAD[P]H Oxidase Activity and Superoxide Formation by a Rac1-Dependent Mechanism. Hypertension 2007;49:201-8
http://doi.org/10.1161/01.HYP.0000251162.14782.d4
Llado L, Xiol X, Figueras J, Ramos E, Memba R, Serrano T, et al. Immunosuppression without steroids in liver transplantation is safe and reduces infection and metabolic complications: results from a prospective multicenter randomized study. J Hepatol. 2006;44(4):710-6 http://doi.org/ 10.1016/j.jhep.2005.12.010
Lucey MR, Abdelmalek MF, Gagliardi R, Granger D, Holt C, Kam I, et al. A comparison of tacrolimus and cyclosporine in liver transplantation: effects on renal function and cardiovascular risk status. Am J Transplant. 2005;5(5):1111-9. http://doi.org/ 10.1111/j.1600-6143.2005.00808.x
Neal DA, Tom BD, Luan J, et al. Is there disparity between risk and incidence of cardiovascular disease after liver transplant? Transplantation 2004;77(1),93-9 http://doi.org/ 10.1097/01.TP.0000100685.70064.90
Nobili V, de Ville de Goyet J. Pediatric post-transplant metabolic syndrome: New clouds on the horizon. Pediatr Transplant 2013;17:216-223 http://doi.org/ 10.1111/petr.12065
Ossoli A, Pavanello C, Calabresi L. „High- density lipoprotein, Lecithin-cholesterol acyltransferase, and Atherosclerosis” Endocrinol Metab 2016;31(2):223-9 http://doi.org/ 10.3803/EnM.2016.31.2.223
Satapathy SK, Charlton MR. Posttransplant Metabolic Syndrome: New Evidence of an Epidemic and Recommendations for Management. Liver transplant 2011;17:1-6 http://doi.org/ 10.1002/lt.22222.
Singh R, Devi S, Gollen R. Role of free radicals in atherosclerosis, diabetes and dyslipidemia. Diabetes Metab Res Rev. 2015; 31(2):113-26 http://doi.org/1 0.1002/dmrr.2558.
Steven S, Daiber A, Dopheide JF, Münzel T, Espinola-Klein C. Peripheral artery disease, redox signaling, oxidative stress - Basic and clinical aspects. Redox Biol. 2017;13;12:787-797 http://doi.org/10.1016/j.redox.2017.04.017
Czubkowski P, Socha P, Pawlowska J. Oxidative stress in liver transplant recipients. Ann Transplant. 2011;16(1):99-108. PMID:21436783
Sundaram SS, Alonso EM, Zeitler P, Yin W, Anand R; SPLIT Research Group. Obesity after pediatric liver transplantation: prevalence and risk factors. J Pediatr Gastroenterol Nutr. 2012;55(6):657-62 http://doi.org/ 10.1097/MPG.0b013e318266243c
Trapp A, Weis M. The Impact of Immunosuppression on Endothelial Function. Journal of Cardiovascular Pharmacology 2005; 45:81-7 PMID:15613984
Trieb M, Horvath A, Birner-Gruenberger R, Spindelboeck W, Stadlbauer V, Taschler U, Curcic S, Stauber RE, Holzer M, Pasterk L, Heinemann A, Marsche G. „Liver disease alters high- density lipoprotein composition, metabolism and function” Biochim Biophys Acta. 2016 ;1861(7):630-8. http://doi.org/ 10.1016/j.bbalip.2016.04.013
Valentine WN, Pagalia DE „Syndromes with increased red cell glutatione (GSH)”. Hemoglobin 1980;4(5-6):799-804 PMID:7440225
Valentine WN, Pagalia DE „Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J.Lab Clin Med. 1967;70(1):158-169. PMID: 6066618
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