The Link between Iron Turnover and Pharmacotherapy in Transplant Patients
Abstract
:1. Introduction
2. Iron Homeostasis
3. Redox Activity of Iron
4. Iron and Immune System
5. Iron and Infections
6. Pharmacotherapy and Iron Turnover in Transplant Patients
7. Pharmacotherapy and Different Types of Anemia in Transplant Patients
7.1. Megaloblastic Anemia
7.2. Aplastic Anemia
7.3. Hemolytic Anemia
8. Conclusions and Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Drug | Model | Link with Anemia | Data Source |
---|---|---|---|
In vitro | |||
Acetylsalicylic acid | Pharmaceutical interaction | Formation of drug–iron complexes (further study needed to assess the biological significance) | Zhang et al. [16] |
Pharmaceutical interaction | Acetylsalicylic acid may chelate endogenous hepatic iron | Schwarz et al. [17] | |
Cell cultures | |||
Acetylsalicylic acid | Microglial cells under inflammatory conditions | Downregulation of hepcidin by inhibition of NF-κB and IL6/JAK2/STAT3 pathways | Li et al. [18] |
Microglial cells under inflammatory conditions | Negative effect on cell iron contents under ‘normal’ conditions, potential to partly reverse iron imbalance under inflammatory conditions | Xu et al. [19] | |
Bovine pulmonary artery endothelial cells | Aspirin at low antithrombotic concentrations induced the synthesis of ferritin protein in a time- and concentration-dependent fashion | Oberle et al. [20] | |
Simvastatin | HepG2 cell line (human liver carcinoma cell line) | Simvastatin significantly suppressed the mRNA expression of hepcidin | Chang et al. [21] |
Vitamin C | HepG2 cell line (human liver carcinoma cell line) | Vitamin C directly inhibits hepcidin expression | Chiu et al. [22] |
Animal model | |||
Sirolimus | Healthy rats | Microcytosis and polyglobulia | Diekmann et al. [23] |
Mice | Export-dependent iron-loss on cellular level | Bayeva et al. [24] | |
Pravastatin | Rat model of cholestasis | Pravastatin raised liver iron content by modulation of heme catabolism and an increase in hepatic iron uptake and storage capacity. | Kolouchova et al. [25] |
Acyclovir | Rats | Acyclovir binds endogenous and exogenous iron | Müller [26] |
Propranolol | Rats | Reduction of cardiac tissue iron uptake | Kramer et al. [27] |
Human model | |||
Sirolimus | Heart transplant patients | Anemia of chronic disease and functional iron deficiency | McDonald et al. [28] |
Renal transplant patients | Anemia, red blood cell microcytosis | Sofroniadou et al. [29] | |
Renal transplant patients | Anemia | Maiorano et al. [30] | |
Renal transplant patients | Anemia due to defective IL-10 dependent inflammatory regulation | Thaunat et al. [31] | |
Everolimus | Renal transplant patients | Anemia, microcytosis | Sánchez Fructuoso et al. [32] |
Liver transplant patients | Anemia | Masetti et al. [33] | |
Cyclosporine | Liver transplant patients | Anemia | Masetti et al. [33] |
Liver transplant patients | Hemolytic anemia (microangiopathic hemolytic anemia—MAHA) related to injury of microvascular endothelial cells and apoptosis | Kanellopoulou et al. [34] | |
Cyclosporine/ Sirolimus/ Steroids | Renal transplant patients | Cyclosporine withdrawal followed by sirolimus immunotherapy resulted in significantly less anemia than sirolimus-cyclosporine-steroids therapy | Friend et al. [35] |
Tacrolimus | Liver and renal transplant patients | Hemolytic anemia (microangiopathic hemolytic anemia—MAHA) related to injury of microvascular endothelial cells and apoptosis | Kanellopoulou et al. [36] |
Prednisone | Renal transplant patients | Pro-erythropoietic, steroid therapy may reduce the severity of anemia in the early post-transplant period | Al-Uzri et al. [37] |
Mycophenolate mofetil | Renal transplant patients | Megaloblastic anemia | Al-Uzri et al. [37] |
Liver transplant patients | Anemia | Al-Uzri et al. [37] | |
Enalapril | Renal transplant patients | Anemia | Vlahakos et al. [38] |
Renal transplant patients | Anemia | Graafland et al. [39] | |
Sulfamethoxazole and trimethoprim | Single patient | Drug-induced immune hemolytic anemia | Frieder et al. [40] Arndt et al. [41] |
Single patient | Drug-induced immune hemolytic anemia with antibodies to both substances | Arndt et al. [42] | |
Single patient | Hemolytic anemia | Chisholm-Burns et al. [43] | |
Ketoconazole, fluconazole | - | - | No data |
Azathioprine | Post-kidney transplantation | Serum iron and serum transferrin saturation increased significantly. No evidence of hemolysis | Habas et al. [44] |
Azathioprine | Post-liver transplantation | Modulation of purine metabolism | Maheshwari et al. [45] |
Azathioprine and prednisolone | Single patient | Successful management of idiopathic pulmonary hemosiderosis | Willms et al. [46] |
Basiliximab | - | - | No data |
Thymoglobulin | - | - | No data |
Rituximab | |||
Amlodipine | Patients with thalassemia major | Amlodipine decreases iron overload and reduces ferritin levels | Fernandes et al. [47] |
Acetylsalicylic acid | A representative cohort of community-dwelling subjects | No association between aspirin use and reduced serum iron or iron saturation | Hammerman-Rozenberg et al. [48] |
Males and females infected or not infected by H. pylori | No effect of low-dose aspirin use on ferritin levels (in males); lower ferritin levels in H. pylori infected subjects using aspirin, compared with both uninfected and infected non-aspirin users (in females) | Kaffes et al. [49] | |
Elderly participants | Aspirin use is associated with lower serum ferritin | Fleming et al. [50] | |
Postmenopausal women | 19% lower mean serum ferritin in aspirin users than in non-users | Liu et al. [51] | |
NSAIDs (loxoprofen, diclofenac, ampiroxicam, naproxen, etodolac) | Patients undergoing chronic hemodialysis | The use of non-aspirin NSAIDs may increase the risk of iron deficiency | Wang et al. [52] |
Fluvastatin | Dyslipidemic end-stage renal disease patients with renal anemia | Fluvastatin treatment decreased high-sensitive C-reactive protein (hs-CRP) and serum prohepcidin (prohormone of hepcidin) levels | Arabul et al. [53]. |
Simvastatin | End-stage renal disease patients with renal anemia | Simvastatin did not significantly change the serum prohepcidin, hs- CRP, or IL-6 concentrations | Li et al. [54] |
Valgancyclovir | - | - | No data |
Allopurinol | Patient with chronic kidney disease | Aplastic anemia | Kim et al. [55] |
Metformin | Patients treated with metformin | Reduction of vitamin B12 | Liu et al. [56] |
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Delijewski, M.; Bartoń, A.; Maksym, B.; Pawlas, N. The Link between Iron Turnover and Pharmacotherapy in Transplant Patients. Nutrients 2023, 15, 1453. https://doi.org/10.3390/nu15061453
Delijewski M, Bartoń A, Maksym B, Pawlas N. The Link between Iron Turnover and Pharmacotherapy in Transplant Patients. Nutrients. 2023; 15(6):1453. https://doi.org/10.3390/nu15061453
Chicago/Turabian StyleDelijewski, Marcin, Aleksandra Bartoń, Beata Maksym, and Natalia Pawlas. 2023. "The Link between Iron Turnover and Pharmacotherapy in Transplant Patients" Nutrients 15, no. 6: 1453. https://doi.org/10.3390/nu15061453
APA StyleDelijewski, M., Bartoń, A., Maksym, B., & Pawlas, N. (2023). The Link between Iron Turnover and Pharmacotherapy in Transplant Patients. Nutrients, 15(6), 1453. https://doi.org/10.3390/nu15061453