Volume 14, Issue 3 ( September 2022 2022)                   Iranian Journal of Blood and Cancer 2022, 14(3): 1-10 | Back to browse issues page

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Bordbar M, Fathpour G, Dehghani S M, Haghpanah S, Molavi Vardanjani H, Fattahi M, et al . The protective role of deferoxamine in the prevention of doxorubicin-induced hepatic fibrosis in children: A randomized controlled clinical trial. Iranian Journal of Blood and Cancer 2022; 14 (3) :1-10
URL: http://ijbc.ir/article-1-1191-en.html
The protective role of deferoxamine in the prevention of doxorubicin-induced hepatic fibrosis in children: A randomized controlled clinical trial
Mohammadreza Bordbar1 , Gholamreza Fathpour * 2, Seyed Mohsen Dehghani3 , Sezaneh Haghpanah4 , Hossein Molavi Vardanjani4 , Mohammadreza Fattahi5 , Mahdi Shahriari6 , Nader Shakibazad6
1- Hematology Research center, Shiraz University of Medical Sciences, Shiraz, Iran
2- Hematology Research center, Shiraz University of Medical Sciences, Shiraz, Iran , dr.reza.fathpour@gmail.com
3- Medical sciences
4- Shiraz Uni
5- Shiraz uni
6- shiraz uni
Abstract:   (907 Views)

Background: This study aimed to investigate the protective role of deferoxamine (DFO) in the prevention of doxorubicin (DOX)-induced hepatic fibrosis in children.
Methods: In this prospective randomized controlled trial, 61 treatment-naïve children (2-18 years) with different types of cancer who referred to a tertiary teaching hospital in the South of Iran were enrolled. They were randomly assigned to 3 groups; group 1 (control, n=21), group 2 (DFO 10 times DOX dose, n=20), group 3 (DFO 50mg/kg, n=20). DFO was administered as an 8-hour continuous intravenous infusion during and after DOX infusion in each chemotherapy cycle. Non-invasive serum markers of liver fibrosis, including AST-to-platelet ratio index (APRI), Fibrosis-4 (FIB-4) score and Fibro Test were measured in each individual. Besides, hepatic Fibro Scan was used after the last course of chemotherapy to estimate the fibrosis degree.
Results: Alanine aminotransferase was mildly increased after treatment compared to before treatment. The treatment with DFO 10 times DOX dose was associated with a significant decline in post-treatment APRI (adjusted odds ratio 0.17; 95% confidence interval 0.03- 0.84. P-value=0.015). The METAVIR fibro scores were in the F0-F1 zone in all participants, and the results were comparable in study groups. No adverse drug effects were reported in the treatment groups.
Conclusion: DOX may not lead to severe liver fibrosis if the maximum cumulative dose allowed is not exceeded. DFO at the dose of 10 times of DOX dose may have a potential protective role against liver fibrosis. More studies with longer follow-up are needed to further assess this issue.

Keywords: Deferoxamine, Doxorubicin, Hepatic fibrosis, Children
Full-Text [PDF 491 kb]   (625 Downloads)    
: Original Article | Subject: Pediatric Hematology & Oncology
Received: 2021/10/12 | Accepted: 2022/07/17 | Published: 2022/09/19
References
1. Mallet V DVV, Roussin C, Bourliere M, Pettinelli M, Giry C, et al. The accuracy of the FIB‐4 index for the diagnosis of mild fibrosis in chronic hepatitis B. Aliment Pharmacol Ther. 2009; 29(4): 409-415. [DOI:10.1111/j.1365-2036.2008.03895.x]
2. McGowan JV CR, Maulik A, Piotrowska I, Walker JM, Yellon DM. Anthracyclinechemotherapy and cardiotoxicity. Cardiovasc Drugs Ther. 2017; 31(1): 63-75. [DOI:10.1007/s10557-016-6711-0]
3. Liu L-L LQ-X, Xia L, Li J, Shao L. Differential effects of dihydropyridine calcium antagonists on doxorubicin-induced nephrotoxicity in rats. Toxicology. 2007; 231(1): 81-90. [DOI:10.1016/j.tox.2006.11.067]
4. Ghibu S DS, Richard C, Guilland J-C, Martin L, Gambert S, et al. General oxidative stress during doxorubicin-induced cardiotoxicity in rats: absence of cardioprotection and low antioxidant efficiency of alpha-lipoic acid. Biochimie. 2012; 94(4): 932-935. [DOI:10.1016/j.biochi.2011.02.015]
5. Mizutani H T-OS, Hiraku Y, Kojima M, Kawanishi S. Mechanism of apoptosis induced by doxorubicin through the generation of hydrogen peroxide. Life Sci 2005; 76(13): 1439-1453. [DOI:10.1016/j.lfs.2004.05.040]
6. Carvalho C SR, Cardoso S, Correia S, Oliveira PJ, Santos MS, et al. Doxorubicin: the good, the bad and the ugly effect. Curr Med Chem. 2009; 16(25): 3267-3285. [DOI:10.2174/092986709788803312]
7. Lee H-J LJ, Lee S-K, Lee S-K, Kim E-C. Differential regulation of iron chelator-induced IL-8 synthesis via MAP kinase and NF-κB in immortalized and malignant oral keratinocytes. BMC cancer. 2007; 7(1): 9-12. [DOI:10.1186/1471-2407-7-176]
8. Leman Yalcintepe EH. Modulation of iron metabolism by iron chelation regulates intracellular calcium and increases sensitivity to doxorubicin. Bosn J Basic Med Sci. 2016; 16(1): 14-18. [DOI:10.17305/bjbms.2016.576]
9. Yamasaki T TS, Sakaida I. Deferoxamine for advanced hepatocellular carcinoma. N Engl J. 2011; 365(6): 576-578. [DOI:10.1056/NEJMc1105726]
10. Elalfy MS, Saber MM, Adly AA, Ismail EA, Tarif M, Ibrahim F, et al. Role of vitamin C as an adjuvant therapy to different iron chelators in young beta-thalassemia major patients: efficacy and safety in relation to tissue iron overload. Eur J Haematol. 2016; 96(3):318-26. [DOI:10.1111/ejh.12594]
11. Hoke EM MC, Shacter E. Desferal inhibits breast tumor growth and does not interfere with the tumoricidal activity of doxorubicin. Free Radic Biol Med. 2005; 39(3): 403-411. [DOI:10.1016/j.freeradbiomed.2005.03.029]
12. Saad SY NT, Al-Rikabi AC. The preventive role of deferoxamine against acute doxorubicin-induced cardiac, renal and hepatic toxicity in rats. Pharmacol Res. 2001;43(3):211-8. [DOI:10.1006/phrs.2000.0769]
13. Lambrecht J VS, Mannaerts I, Reynaert H, van Grunsven LA. Prospects in non-invasive assessment of liver fibrosis: Liquid biopsy as the future gold standard? Biochim Biophys Acta Mol Basis Dis. 2018; 1864(4): 1024-1036. [DOI:10.1016/j.bbadis.2018.01.009]
14. Shah AG LA, Murray K, Tetri BN, Contos MJ, Sanyal AJ, et al. Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2009; 7(10): 1104-1112. [DOI:10.1016/j.cgh.2009.05.033]
15. Unalp‐Arida A, Ruhl CE. Liver fibrosis scores predict liver disease mortality in the United States population. Hepatology 2017; 66(1): 84-95. [DOI:10.1002/hep.29113]
16. Chindamo MC BJ, Luiz RR, Fouchard-Hubert I, Pannain VLN, de Araújo Neto JM, et al. Fibrosis assessment using FibroMeter combined to first generation tests in hepatitis C. World J Hepatol. 2017; 9(6): 310. [DOI:10.4254/wjh.v9.i6.310]
17. Lin ZH XY, Dong QJ, Wang Q, Jiang XJ, Zhan SH, et al. Performance of the aspartate aminotransferase‐to‐platelet ratio index for the staging of hepatitis C‐related fibrosis: an updated meta‐analysis. Hepatology. 2011; 53(3): 726-736. [DOI:10.1002/hep.24105]
18. Xiao G YJ, Yan L. Comparison of diagnostic accuracy of aspartate aminotransferase to platelet ratio index and fibrosis‐4 index for detecting liver fibrosis in adult patients with chronic hepatitis B virus infection: a systemic review and meta‐analysis. Hepatology. 2015; 61(1): 292-302. [DOI:10.1002/hep.27382]
19. Thiele M MB, Hansen JF, Detlefsen S, Antonsen S, Krag A. Accuracy of the enhanced liver fibrosis test vs FibroTest, elastography, and indirect markers in detection of advanced fibrosis in patients with alcoholic liver disease. Gastroenterology. 2018; 154(5): 1369-1379. [DOI:10.1053/j.gastro.2018.01.005]
20. Lurie Y WM, Cytter-Kuint R, Shteingart S, Lederkremer GZ. Non-invasive diagnosis of liver fibrosis and cirrhosis. World J Gastroenterol. 2015; 21(41): 11567-11583. [DOI:10.3748/wjg.v21.i41.11567]
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