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Recent Advances in Inflammation & Allergy Drug Discovery

Recent Advances in Inflammation & Allergy Drug Discovery

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ISSN (Print): 2772-2708
ISSN (Online): 2772-2716

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Research Article

Monitoring Tacrolimus and Cyclosporine Blood Trough Levels and the Capacity of Anti-oxidant after Kidney Transplantation: A Patent Perspective

Author(s): Zahra Tolou-Ghamari*

Volume 19, Issue 3, 2025

Published on: 10 December, 2024

Page: [374 - 379] Pages: 6

DOI: 10.2174/0127722708319486241202113259

Price: $65

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Abstract

Background: It is well known that acute or chronic kidney injury could be due to free radicals and pro-oxidants. This investigation aimed to monitor tacrolimus or cyclosporine blood trough levels and anti-oxidant capacity after kidney transplantation.

Methods: There was no intervention in the routine management of transplant recipients. The sample size (n=70) included healthy individuals and kidney-transplanted recipients (n=25 on tacrolimus and n=10 on cyclosporine). The study population was matched for age. The attained information was examined by using the Statistical Package (SPSS Inc, Chicago, IL, USA). The significance level was considered as P ≤ 0.05.

Results: In healthy individuals, the mean ± SD for the capacity of antioxidants was 91.9 ± 16.6 (u/ml), which was significantly higher when compared to the mean value of 28.5 ± 22.6 (u/ml) versus 24.7 ± 25.5 (u/ml), kidney recipients with tacrolimus versus cyclosporine (P ≤ 0.04) as immunosuppressive drugs. The mean value of tacrolimus levels was 14.6 ± 6.4 (ng/ml). The correlation between tacrolimus and cyclosporine trough levels and anti-oxidant capacity was 0.19 (P ≤ 0.14). There were no significant differences regarding age in cases and controls (P ≤ 0.42).

Conclusion: This study showed that the capacity of anti-oxidants in kidney transplant recipients, those on tacrolimus or cyclosporine, might be lower than in healthy individuals. Subsequent investigations are recommended to delve into the therapeutic consequences of the influence of antioxidant therapies on the clinical outcomes of transplanted recipients.

Keywords: Anti-oxidant capacity, tacrolimus, cyclosporine, kidney, transplantation, recipient, chitosan nanoparticles.

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Graphical Abstract

Graphical abstract illustrating key findings of the study

[1]
Manns B, Hemmelgarn B, Tonelli M, et al. The cost of care for people with chronic kidney disease. Can J Kidney Health Dis 2019; 6: 2054358119835521.
[http://dx.doi.org/10.1177/2054358119835521]
[2]
Collister D, Pannu N, Ye F, et al. Health care costs associated with AKI. Clin J Am Soc Nephrol 2017; 12(11): 1733-43.
[http://dx.doi.org/10.2215/CJN.00950117]
[3]
Daenen K, Andries A, Mekahli D, Van Schepdael A, Jouret F, Bammens B. Oxidative stress in chronic kidney disease. Pediatr Nephrol 2019; 34(6): 975-91.
[http://dx.doi.org/10.1007/s00467-018-4005-4]
[4]
Tabriziani H, Lipkowitz MS, Vuong N. Chronic kidney disease, kidney transplantation and oxidative stress: a new look to successful kidney transplantation. Clin Kidney J 2018; 11(1): 130-5.
[http://dx.doi.org/10.1093/ckj/sfx091]
[5]
Rajbala A, Sane AS, Shah PR, et al. Effect of renal transplantation (surgical stress) on serum levels of oxidants and reducing system. Panminerva Med 1999; 41(1): 31-4.
[6]
Dennis J, Witting P. Protective Role for Antioxidants in Acute Kidney Disease. Nutrients 2017; 9(7): 718.
[http://dx.doi.org/10.3390/nu9070718]
[7]
Gyurászová M, Gurecká R, Bábíčková J, Tóthová Ľ. Oxidative Stress in the Pathophysiology of Kidney Disease: Implications for Noninvasive Monitoring and Identification of Biomarkers. Oxid Med Cell Longev 2020; 2020: 1-11.
[http://dx.doi.org/10.1155/2020/5478708]
[8]
Basile DP, Anderson MD, Sutton TA. Pathophysiology of acute kidney injury. Compr Physiol 2012; 2(2): 1303-53.
[http://dx.doi.org/10.1002/cphy.c110041]
[9]
Fonseca I. Evidence-based practice, step by step: searching for the evidence. Am J Nurs 2014; 110(5): 41-7.
[http://dx.doi.org/10.1097/01]
[10]
Nafar M. Oxidative stress in kidney transplantation: Causes, consequences, and potential treatment. Iran J Kidney Dis 2011; 5(6): 357-72.
[11]
Chrzanowska M, Kamińska J, Głyda M, Duda G, Makowska E. Antioxidant capacity in renal transplant patients. Pharmazie 2010.
[12]
Tariq M, Morais C, Sobki S, Al Sulaiman M, Al Khader A. N-acetylcysteine attenuates cyclosporin-induced nephrotoxicity in rats. Nephrol Dial Transplant 1999; 14(4): 923-9.
[http://dx.doi.org/10.1093/ndt/14.4.923]
[13]
Manrique J, Errasti P, Lavilla J, et al. Treatment of hyperhomocysteinemia after renal transplantation. Transplant Proc 2003; 35(5): 1742-4.
[http://dx.doi.org/10.1016/S0041-1345(03)00628-6]
[14]
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. Am J Nephrol 2005; 25(3): 250-5.
[http://dx.doi.org/10.1159/000086079]
[15]
Cofan F, Cofan M, Campos B, Guerra R, Campistol JM, Oppenheimer F. Effect of calcineurin inhibitors on low-density lipoprotein oxidation. Transplant Proc 2005; 37(9): 3791-3.
[http://dx.doi.org/10.1016/j.transproceed.2005.10.068]
[16]
Perrea DN, Moulakakis KG, Poulakou MV, Vlachos IS, Papachristodoulou A, Kostakis AI. Correlation between oxidative stress and immunosuppressive therapy in renal transplant recipients with an uneventful postoperative course and stable renal function. Int Urol Nephrol 2006; 38(2): 343-8.
[http://dx.doi.org/10.1007/s11255-006-0054-x]
[17]
Mazdak H, Tolou Ghamari Z, Gholampour M. Bladder cancer: total antioxidant capacity and pharmacotherapy with vitamin-E. Int Urol Nephrol 2020; 52(7): 1255-60.
[http://dx.doi.org/10.1007/s11255-020-02411-3]
[18]
Tolou-Ghamari Z, Mortazavi M, Palizban AA, Najafi MR. The investigation of correlation between Iminoral concentration and neurotoxic levels after kidney transplantation. Adv Biomed Res 2015; 4(1): 59.
[http://dx.doi.org/10.4103/2277-9175.151876]
[19]
Tadayon F, Shariati A, Tolou-Ghamari Z. Type of vascular anastomosis and early outcome after kidney transplantation. Urologiia 2021.
[20]
Kurutas EB. The importance of antioxidants which play the role in cellular response against oxidative/nitrosative stress: current state. Nutr J 2015; 15(1): 71.
[http://dx.doi.org/10.1186/s12937-016-0186-5]
[21]
Tolou-Ghamari Z. Tacrolimus and cyclosporin pharmacotherapy, detection methods, cytochrome p450 enzymes after heart transplantation. Cardiovasc Hematol Agents Med Chem 2024; 22(2): 106-13.
[http://dx.doi.org/10.2174/1871525721666230726150021]
[22]
Tolou Ghamari Z, Palizban AA. Tacrolimus Pharmacotherapy: Infectious Complications and Toxicity in Organ Transplant Recipients; An Updated Review. Curr Drug Res Rev 2023.
[http://dx.doi.org/10.2174/0125899775259326231212073240]
[23]
Tolou-Ghamari Z, Palizban AA, Michael Tredger J. Clinical monitoring of tacrolimus after liver transplantation using pentamer formation assay and microparticle enzyme immunoassay. Drugs R D 2004; 5(1): 17-22.
[http://dx.doi.org/10.2165/00126839-200405010-00003]
[24]
Tolou-Ghamari Z, Wendon J, Tredger JM. In vitro pentamer formation as a biomarker of tacrolimus-related immunosuppressive activity after liver transplantation. Clin Chem Lab Med 2000; 38(11): 1209-11.
[http://dx.doi.org/10.1515/CCLM.2000.190]
[25]
Tolou-Ghamari Z, Palizban AA. Laboratory Monitoring of Cyclosporine Pre-Dose Concentration (C 0) after Kidney Transplantation in Isfahan. IJMS 2003; 28(2): 81-5.
[26]
Carcy R, Cougnon M, Poet M, et al. Targeting oxidative stress, a crucial challenge in renal transplantation outcome. Free Radic Biol Med 2021; 169: 258-70.
[http://dx.doi.org/10.1016/j.freeradbiomed.2021.04.023]
[27]
Mittal M, Siddiqui MR, Tran K, Reddy SP, Malik AB. Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal 2014; 20(7): 1126-67.
[http://dx.doi.org/10.1089/ars.2012.5149]
[28]
Cau SBA, Carneiro FS, Tostes RC. Differential modulation of nitric oxide synthases in aging: therapeutic opportunities. Front Physiol 2012; 3: 218.
[http://dx.doi.org/10.3389/fphys.2012.00218]
[29]
Kwiatkowska M, Oldakowska-Jedynak U, Wojtaszek E, Glogowski T, Malyszko J. Potential Effects of Immunosuppression on Oxidative Stress and Atherosclerosis in Kidney Transplant Recipients. Oxid Med Cell Longev 2021; 2021(1): 6660846.
[http://dx.doi.org/10.1155/2021/6660846]
[30]
Thongprayoon C, Hansrivijit P, Kovvuru K, et al. Impacts of High Intra- and Inter-Individual Variability in Tacrolimus Pharmacokinetics and Fast Tacrolimus Metabolism on Outcomes of Solid Organ Transplant Recipients. J Clin Med 2020; 9(7): 2193.
[http://dx.doi.org/10.3390/jcm9072193]
[31]
Tolou-Ghamari Z. Nephro and neurotoxicity of calcineurin inhibitors and mechanisms of rejections: A review on tacrolimus and cyclosporin in organ transplantation. J Nephropathol 2012; 1(1): 23-30.
[http://dx.doi.org/10.5812/jnp.6]
[32]
Elsamanoudy AZ, El-Bassossy HM, Hassanien MA, Bima A, Ghoneim FM. Renal oxidative stress and inflammatory response in perinatal Cyclosporine-A exposed rat progeny and its relation to gender. J Microsc Ultrastruct 2019; 7(1): 44-9.
[http://dx.doi.org/10.4103/JMAU.JMAU_52_18]
[33]
Abd-Eldayem AM, Makram SM, Messiha BAS, Abd-Elhafeez HH, Abdel-Reheim MA. Cyclosporine-induced kidney damage was halted by sitagliptin and hesperidin via increasing Nrf2 and suppressing TNF-α, NF-κB, and Bax. Sci Rep 2024; 14(1): 7434.
[http://dx.doi.org/10.1038/s41598-024-57300-x]
[34]
Liu C, Zhu P, Fujino M, et al. 5-aminolaevulinic acid (ALA), enhances heme oxygenase (HO)-1 expression and attenuates tubulointerstitial fibrosis and renal apoptosis in chronic cyclosporine nephropathy. Biochem Biophys Res Commun 2019; 508(2): 583-9.
[http://dx.doi.org/10.1016/j.bbrc.2018.11.175]
[35]
Lu Y, Li CF, Ping NN, et al. Hydrogen‐rich water alleviates cyclosporine A‐induced nephrotoxicity via the Keap1/Nrf2 signaling pathway. J Biochem Mol Toxicol 2020; 34(5): e22467.
[http://dx.doi.org/10.1002/jbt.22467]
[36]
Al-Massarani G, Vacher-Coponat H, Paul P, et al. Impact of immunosuppressive treatment on endothelial biomarkers after kidney transplantation. Am J Transplant 2008; 8(11): 2360-7. [x.].
[http://dx.doi.org/10.1111/j.1600-6143.2008.02399.x]
[37]
Tolou-Ghamari Z. Monitoring tacrolimus after liver transplantation; consideration of alternative techniques and the influence of clinical status. London: King’s College 1999.
[38]
Tolou-Ghamari Z, Palizban A, Gharavi M. Cyclosporin trough concentration-rejection relationship after kidney transplantation. Indian J Pharmacol 2003; 35(6): 395-6.
[39]
Tolou-Ghamari Z, Sanei B. Prograf Concentrations in Liver Transplantation: Correlation with Headache and Other Neurotoxic Complications? Thrita 2016; 5(1)
[40]
Tolou-Ghamari Z. Monitoring heart transplant recipients in order to investigate immunosuppressive drug absorption using pharmacokinetics parameters and its’ correlation with nephrotoxicity. AJECR 2019; 6(4)
[41]
Tolou-Ghamari Z, Palizban AA, Tredger JM. Modelling tacrolimus AUC in acute and chronic liver disease immediately after transplant. Transplantationsmedizin. Organ der Deutschen Transplantationsgesellschaft 2004; 16(2): 109-11.
[42]
Tolou-Ghamari Z, Palizban AA, Wendon J, Tredger JM. Pharmacokinetics of tacrolimus immediately after liver transplantation. Transplantationsmedizin. Organ der Deutschen Transplantationsgesellschaft 2004; 16(2): 112-6.
[43]
Ammar M, Yaich S, Hakim A, et al. Tacrolimus trough level and oxidative stress in Tunisian kidney transplanted patients. Ren Fail 2024; 46(1): 2313863.
[http://dx.doi.org/10.1080/0886022X.2024.2313863]
[44]
Frijhoff J, Winyard PG, Zarkovic N, et al. Clinical relevance of biomarkers of oxidative stress. Antioxid Redox Signal 2015; 23(14): 1144-70.
[http://dx.doi.org/10.1089/ars.2015.6317]
[45]
Stefanović NZ, Cvetković TP, Jevtović-Stoimenov TM, et al. Potential role of tacrolimus in erythrocytes’ antioxidative capacity in long-term period after renal transplantation. Eur J Pharm Sci 2015; 70: 132-9.
[http://dx.doi.org/10.1016/j.ejps.2015.01.013]
[46]
de Cal M, Silva S, Cruz D, et al. Oxidative stress and ‘monocyte reprogramming’ after kidney transplant: a longitudinal study. Blood Purif 2008; 26(1): 105-10.
[http://dx.doi.org/10.1159/000110575]
[47]
Joncquel M, Labasque J, Demaret J, et al. Targeted Metabolomics Analysis Suggests That Tacrolimus Alters Protection against Oxidative Stress. Antioxidants 2023; 12(7): 1412.
[http://dx.doi.org/10.3390/antiox12071412]
[48]
Kidokoro K, Satoh M, Nagasu H, et al. Tacrolimus induces glomerular injury via endothelial dysfunction caused by reactive oxygen species and inflammatory change. Kidney Blood Press Res 2012; 35(6): 549-57.
[http://dx.doi.org/10.1159/000339494]
[49]
Stumpf J, Budde K, Witzke O, et al. Fixed low dose versus concentration-controlled initial tacrolimus dosing with reduced target levels in the course after kidney transplantation: results from a prospective randomized controlled non-inferiority trial (Slow & Low study). EClinicalMedicine 2024; 67: 102381.
[http://dx.doi.org/10.1016/j.eclinm.2023.102381]
[50]
Deng S, Jin T, Zhang L, Bu H, Zhang P. Mechanism of tacrolimus-induced chronic renal fibrosis following transplantation is regulated by ox-LDL and its receptor, LOX-1. Mol Med Rep 2016; 14(5): 4124-34.
[http://dx.doi.org/10.3892/mmr.2016.5735]
[51]
Jiang YJ, Cui S, Luo K, et al. Nicotine exacerbates tacrolimus-induced renal injury by programmed cell death. Korean J Intern Med (Korean Assoc Intern Med) 2021; 36(6): 1437-49.
[http://dx.doi.org/10.3904/kjim.2021.326]
[52]
Moreno JM, Ruiz MC, Ruiz N, et al. Modulation factors of oxidative status in stable renal transplantation. Transplant Proc 2005; 37(3): 1428-30.
[http://dx.doi.org/10.1016/j.transproceed.2005.02.037]
[53]
Tolou-Ghamari Z. Nosocomial Urinary Tract Infections in a Tertiary Hospital; Preliminary Study of Antibiotics Susceptibility Testing and Pathogen Types. Antiinfect Agents 2024; 22(2): e251023222696.
[http://dx.doi.org/10.2174/0122113525258170231016081424]
[54]
Tolou-Ghamari Z. Investigation of Nosocomial Urianary Tract Infections Post transplanatation, Main Pathogens, and Sensitivity Tests. Curr Drug Ther 2023.
[http://dx.doi.org/10.2174/0115748855271275231115064229]
[55]
Tolou-Ghamari Z. Preliminary Study of Antibiotics Susceptibility Testing and Pathogens Associated with Nosocomial Infections in a Tertiary Hospital. Antiinfect Agents 2024; 22(2): e271023222865.
[http://dx.doi.org/10.2174/0122113525259607231020063637]
[56]
Rodrigues-Diez R, González-Guerrero C, Ocaña-Salceda C. Calcineurin inhibitors cyclosporine A and tacrolimus induce vascular inflammation and endothelial activation through TLR4 signaling. Sci Rep 2016; 6: 27915.
[http://dx.doi.org/10.1038/srep27915]

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