Novel Insights into Oxidative Stress and Antioxidant Enzymes in Acute Antibody-Mediated Rejection of Renal Allografts
Abstract
Introduction. Antibody mediated rejection (AMR) is a major challenge in kidney transplantation and adversely affects allograft survival. Oxidative stress (OS) is implicated in AMR pathogenesis by triggering inflammation, apoptosis and fibrosis in the graft tissue. However, the status of OS and antioxidant defense in AMR patients remains unclear. We aimed to evaluate the levels of OS markers and antioxidant enzymes in AMR patients.
Methods. We conducted a case-control study involving 22 biopsy-proven AMR patients (test group) and 14 kidney recipients with stable graft function (control group). Serum total oxidant status (TOS), total antioxidant capacity (TAC), total thiol groups, nitric oxide (NO), 8-isoprostane (8-IP) were determined and activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were measured by spectrophotometric methods.
Results. Data analysis showed significant increases in TOS, TAC and 8-IP levels together with marked reductions in NO and total thiol groups in AMR patients. CAT and GPx activities did not differ between groups, however SOD activity was significantly lower in AMR patients.
Conclusion. Our study showed increased OS and impaired antioxidant defense in AMR patients. NO level may serve as a potential biomarker of OS severity and immune response in AMR. Further studies are required to elucidate the mechanisms and consequences of OS in AMR and to explore the therapeutic potential of antioxidants.
Downloads
References
Kannan K, Jain SK. Oxidative stress and apoptosis. Pathophysiology. 2000;7(3):153-63.
Czerska M, Mikolajewska K, Zielinski M, Gromadzinska J, Wasowicz W. Today’s oxidative stress markers. 2015.
Liguori I, Russo G, Curcio F, et al. Oxidative stress, aging, and diseases. Clinical interventions in aging. 2018;13:757.
Cottone S, Palermo A, Vaccaro F, et al. In renal transplanted patients inflammation and oxidative
stress are interrelated. Transplantation proceedings. 2006;38(4):1026-30.
Daenen K, Andries A, Mekahli D, et al. Oxidative
stress in chronic kidney disease. Pediatric Nephrology. 2019;34(6):975-91.
Štrebl P, Horčička Jr V, Krejči K, et al. Oxidative
stress after kidney transplantation: The role of immunosuppression. Dialysis & Transplantation.
;39(9):391-4.
Vural A, Yilmaz MI, Caglar K, et al. Assessment of oxidative stress in the early posttransplant period: comparison of cyclosporine A and tacrolimus-
based regimens. American journal of nephrology.
;25(3):250-5.
Pérez Fernandez R, Martín Mateo M, De Vega L, et
al. Antioxidant enzyme determination and a study of
lipid peroxidation in renal transplantation. Renal failure. 2002;24(3):353-9.
Simic-Ogrizovic S, Simic T, Reljic Z, et al. Markers of oxidative stress after renal transplantation. Transplant International. 1998;11(1):S125-S9.
Cristol J-P, Vela C, Maggi M-F, Descomps B, Mourad
G. Oxidative Stress and Lipid Abnormalities in Renal Transplant Recipients with or without Chronic Rejection1. Transplantation. 1998;65(10):1322-8.
Eftekhar E, Hajirahimkhan A, Taghizadeh Afshari A, Nourooz-Zadeh J. Plasma glutathione peroxidase activity in kidney recipients with and without adverse outcome. Renal failure. 2012;34(5):628-33.
Raj DS, Lim G, Levi M, Qualls C, Jain SK. Advanced glycation end products and oxidative stress are increased in chronic allograft nephropathy. American Journal of Kidney Diseases. 2004;43(1):154-60.
Land WG. Ageing and immunosuppression in kidney transplantation. Exp Clin Transplant. 2004;2(2):229.
Perrea DN, Moulakakis KG, Poulakou MV, et
al. Correlation between oxidative stress and immunosuppressive therapy in renal transplant recipients with an uneventful postoperative course and stable renal function. International urology and nephrology. 2006;38(2):343-8.
Lucas JG, Co JP, Nwaogwugwu UT, Dosani I, Sureshkumar KK. Antibody-mediated rejection in
kidney transplantation: an update. Expert opinion on pharmacotherapy. 2011;12(4):579-92.
Adler S, Baker P, Johnson R, et al. Complement membrane attack complex stimulates production
of reactive oxygen metabolites by cultured rat
mesangial cells. The Journal of clinical investigation. 1986;77(3):762-7.
Nafar M, Sahraei Z, Salamzadeh J, Samavat S, Vaziri ND. Oxidative stress in kidney transplantation: causes, consequences, and potential treatment. Iranian journal of kidney diseases. 2011;5(6):357.
Tabriziani H, Lipkowitz MS, Vuong N. Chronic kidney disease, kidney transplantation and oxidative stress: a new look to successful kidney transplantation. Clinical Kidney Journal. 2017.
Roufosse C, Simmonds N, Clahsen-van Groningen M, et al. A 2018 reference guide to the Banff classification of renal allograft pathology. Transplantation.
;102(11):1795-814.
Benzie IF, Strain JJ. The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Analytical biochemistry. 1996;239(1):70-6.
Gay C, Collins J, Gebicki JM. Hydroperoxide assay with the ferric–xylenol orange complex. Analytical biochemistry. 1999;273(2):149-55.
Sánchez-Rodríguez MA, Mendoza-Núñez VM. Oxidative stress indexes for diagnosis of health or disease in humans. Oxid Med Cell Longev. 2019;2019.
Hu M, Dillard C. Plasma SH and GSH measurement. Methods Enzymol. 1994;233(385):87.
Sun J, Zhang X, Broderick M, Fein H. Measurement of nitric oxide production in biological systems by using Griess reaction assay. Sensors. 2003;3(8):276-84.
Agarwal A, Kim Y, Matas AJ, Alam J, Nath KA. Gas-generating systems in acute renal allograft rejection in the rat: Co-induction of heme oxygenase and nitric oxide synthase1, 2. Transplantation. 1996;61(1):93-8.
Bellos JK, Perrea DN, Theodoropoulou E, et al. Clinical correlation of nitric oxide levels with acute rejection
in renal transplantation. International urology and nephrology. 2011;43(3):883-90.
Carrillo-Ibarra S, Cerrillos-Gutiérrez JI, Escalante-Núñez A, et al. The oxidative and inflammatory state in patients with acute renal graft dysfunction treated with tacrolimus. Oxid Med Cell Longev. 2016;2016.
Banerjee D, Mazumder S, Sinha AK. Involvement of nitric oxide on calcium mobilization and arachidonic
acid pathway activation during platelet aggregation with different aggregating agonists. International journal of biomedical science: IJBS. 2016;12(1):25.
Lucke-Wold B, Logsdon A, Li X, et al. Reduced endothelial basal nitric oxide induces leukocyte adhesion through Src-dependent phosphorylation of constitutive intercellular adhesion molecule-1. The FASEB Journal. 2016;30(1_ supplement):723.11-.11.
Vos IH, Joles JA, Rabelink TJ, editors. The role of nitric oxide in renal transplantation. Seminars in nephrology; 2004: Elsevier.
Lubos E, Handy DE, Loscalzo J. Role of oxidative
stress and nitric oxide in atherothrombosis. Frontiers in bioscience: a journal and virtual library. 2008;13:5323.
Pierini D, Bryan NS. Nitric oxide availability as a marker of oxidative stress. Advanced Protocols in Oxidative Stress III: Springer; 2015. p. 63-71.
Chandra M, Panchatcharam M, Miriyala S. Biomarkers in ROS and role of isoprostanes in oxidative stress. Free Radicals and Diseases. 2016:131-48.
Ikizler TA, Morrow J, Roberts L, et al. Plasma F2-isoprostane levels are elevated in chronic hemodialysis patients. Clinical nephrology. 2002;58(3):190-7.
Simmons EM, Langone A, Sezer MT, et al. Effect of renal transplantation on biomarkers of inflammation and oxidative stress in end-stage renal disease patients. Transplantation. 2005;79(8):914-9.
Cracowski JL, Souvignet C, Quirin N, et al. Urinary F2-isoprostanes formation in kidney transplantation. Clinical transplantation. 2001;15(1):58-62.
Campise M, Bamonti F, Novembrino C, et al. Oxidative stress in kidney transplant patients1. Transplantation. 2003;76(10):1474-8.
Soleymanian T, Ranjbar A, Alipour M, Ganji MR, Najafi
I. Impact of kidney transplantation on biomarkers of oxidative stress and inflammation. Iranian journal of kidney diseases. 2015;9(5):400-5.
Aveles PR, Criminácio CR, Gonçalves S, et al. Association between biomarkers of carbonyl stress with increased systemic inflammatory response in different stages of chronic kidney disease and after renal transplantation. Nephron Clinical Practice. 2010;116(4):c294-c9.
Chrzanowska M, Kamińska J, Głyda M, Duda G, Makowska E. Antioxidant capacity in renal transplant patients. Die Pharmazie-An International Journal of Pharmaceutical Sciences. 2010;65(5):363-6.
Fonseca I, Reguengo H, Almeida M, et al. Oxidative stress in kidney transplantation: malondialdehyde is an early predictive marker of graft dysfunction. Transplantation. 2014;97(10):1058-65.
Vostálová J, Galandáková A, Svobodová AR, et al. Time-course evaluation of oxidative stress-related biomarkers after renal transplantation. Renal failure. 2012;34(4):413-9.
MacMillan-Crow LA, Cruthirds DL, Ahki KM, Sanders PW, Thompson JA. Mitochondrial tyrosine nitration precedes chronic allograft nephropathy. Free Radical Biology and Medicine. 2001;31(12):1603-8.
Wang P-X, Sanders PW. Immunoglobulin light chains generate hydrogen peroxide. Journal of the American Society of Nephrology. 2007;18(4):1239-45.
Cvetković T, Veličković-Radovanović R, Stojanović
D, et al. Oxidative and nitrosative stress in stable
renal transplant recipients with respect to the immunosuppression protocol–differences or similarities?Journal of Medical Biochemistry. 2015;34(3):295.
Díaz-De la Cruz EN, Cerrillos-Gutiérrez JI, García-Sánchez A, et al. The alteration of pro-inflammatory cytokines and oxidative stress markers at six-month post-living kidney donation. Frontiers in medicine. 2020;7:382.
Kumar A, Hammad A, Sharma AK, et al. Oxidative stress in kidney transplant biopsies. Exp Clin Transplant. 2015;13(Suppl 1):207-13.
Antolini F, Valente F, Ricciardi D, Fagugli R. Normalization of oxidative stress parameters after kidney transplant
is secondary to full recovery of renal function. Clinical nephrology. 2004;62(2):131-7.
Sofic E, Rustembegovic A, Kroyer G, Cao G. Serum antioxidant capacity in neurological, psychiatric, renal diseases and cardiomyopathy. Journal of neural transmission. 2002;109(5-6):711-9.
