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Gülüzar Özbolat
Gülüzar Özbolat
Faculty of Health Science, Sinop University, Sinop, Turkey
-
Arash Alizadeh Yegani
Arash Alizadeh Yegani
Department of Pharmacology, Faculty of Veterinary, Mustafa Kemal University, Hatay, Turkey
Published Date
- Dec 31, 2021
Effects of Curcumin on Iron Overload in Rats
Abstract
Background: Iron overload, common in patients with hematological disorders, is a key target in drug development. This study investigated the effects of curcumin on iron overload in rats.
Methods: Forty male Wistar rats weighing 139.78 ± 11.95 gm (Mean ± SD) were divided into three equal groups: (i) controls; (ii) iron overload group that received six doses of iron dextran 1000 mg/kg–1 by intraperitoneal injections (i.p.); and (iii) iron overload curcumin group that received six doses of curcumin (1000 mg/kg BW by i.p.). In addition to six doses of iron dextran 1000 mg/kg–1 by i.p., we studied the effects of curcumin on liver function enzymes (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]); antioxidant enzymes (malondialdehyde [MDA], total oxidant status [TOS], total antioxidant status [TAS]); hematological parameters (hemoglobin [Hb], hematocrit [Hct], red blood cells [RBC], white blood cells [WBC], mean corpus volume [MCV], mean corpuscular hemoglobin [MCH], mean corpuscular hemoglobin concentration [MCHC]); and iron parameters (serum iron profile, transferrin, total iron-binding capacity [TIBC], ferritin, and transferrin saturation [TS%]).
Results: Curcumin caused a significant decrease in the Hct and Hb concentrations in Group III (P < 0.05). It also significantly reduced the serum levels of ALT (52.45 ± 4.51 vs 89.58 ± 4.65 U/L) and AST (148.03 ± 6.47 vs 265.27 ± 13.02 U/L) at the end of the study (P < 0.05). The TIBC, transferrin levels, and TS significantly decreased when the rats were administered curcumin serum iron (P < 0.05). The TAS level significantly increased in Group III in comparison to Group I (the control group) (P < 0.05). At the end of the study, curcumin significantly reduced the serum levels of TOS (12.03 ± 2.8 vs 16.95 ± 5.05 mmol H2O2/L) while the TAS (1.98 ± 0.42 vs 1.06 ± 0.33 mmol Trolox equiv./L) was increased.
Conclusion: The findings of the present study suggest the therapeutic potential of curcumin against iron overload.
Keywords:
curcumin, iron overload, TIBC, TAS, TOS, MDA
References
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[26] Porter, J. B. (2007). Concepts and goals in the management of transfusional iron overload. American Journal of Hematology, vol. 82, no. 12, pp. 1136–1139.
[27] Shah, N. R. (2017). Advances in iron chelation therapy: transitioning to a new oral formulation. Drugs in Context, vol. 6, p. 212502.
[28] Sheth, S. (2014). Iron chelation: an update. Current Opinion in Hematology, vol. 21, no. 3, pp. 179–185.
[29] Davis, B. A. and Porter, J. B. (2000). Long-term outcome of continuous 24-hour desferoxamine infusion via indwelling intravenous catheters in high-risk beta thalassemia. Blood, vol. 95, no. 4, pp. 1229–1236.
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[32] Borgna-Pignatti, C., Cappellini, M. D., De Stefano, P., et al. (2006). Cardiac morbidity and mortality in deferoxamine- or deferiprone treated patients with thalassemia major. Blood, vol. 107, no. 9, pp. 3733–3737.
[33] Xia, S., Zhang, W., Huang, L., et al. (2013). Comparative efficacy and safety of deferoxamine, deferiprone and deferasirox on severe thalassemia: a meta-analysis of 16 randomized controlled trials. PLoS One, vol. 8, no. 12, p. e82662.
[34] Hejazi, S., Safari, O., Arjmand, R., et al. (2016). Effect of combined versus monotherapy with deferoxamine and deferiprone in iron overloaded thalassemia patients: a randomized clinical trial. International Journal of Pediatrics, vol. 4, no. 30, pp. 1959–1965.
[35] Caro J., Huybrechts, K. F., and Green, T. C. (2002). Estimates of the effect on hepatic iron of oral deferiprone compared with subcutaneous desferrioxamine for treatment of iron overload in thalassemia major: a systematic review. BMC Blood Disorders, vol. 2, no. 1, p. 4.
[36] Ejaz, M. S., Baloch, S., and Arif, F. (2015). Efficacy and adverse effects of oral chelating therapy (deferasirox) in multi-transfused Pakistani children with β-thalassemia major. Pakistan Journal of Medical Sciences, vol. 31, no. 3, pp. 621–625.
[37] Senol, S. F., Tiftik, E. C., Unal, S., et al. (2016). Quality of life, clinical effectiveness, and satisfaction in patients with beta thalassemia major and sickle cell anemia receiving deferasirox chelation therapy. Journal of Basic and Clinical Pharmacy, vol. 7, no. 2, pp. 49–59.
[38] Du, X.-X., Xu, H.-M., Jiang, H., et al. (2012). Curcumin protects nigral dopaminergic neurons by iron-chelation in the 6-hydroxydopamine rat model of Parkinson’s disease. Neuroscience Bulletin, vol. 28, no. 3, pp. 253–258.
[39] Messne, D. J., Sivam, G., and Kowdley, K. V. (2009). Curcumin reduces the toxic effects of iron loading in rat liver. Liver International, vol. 29, no. 1, pp. 63–72.
[40] Crisponi, G., Nurchi, V. M., and Zoroddu, M. A. (2014). Iron chelating agents for Iron overload diseases. Thalassemia Reports, vol. 4, no. 2.
[41] Erdincler, D. S., Seven, A., Inci, F., et al. (1997). Lipid peroxidation and antioxidant status in experimental animals: effects of aging and hypercholesterolemic diet. Clinica Chimica Acta, vol. 265, no. 1, pp. 77–84.
[42] Reardon, T. F. and Allen, D. G. (2009). Iron injections in mice increase skeletal muscle iron content, induce oxidative stress and reduce exercise performance. Experimental Physiology, vol. 94, no. 6, pp. 720–730.
[43] Merono, T., Gomez, L., Sorroche, P., et al. (2011). High risk of cardiovascular disease in iron overload patients. European Journal of Clinical Investigation, vol. 41, no. 5, pp. 479–486.
[44] Özbolat, G. and Yegani, A. A. (2020). Synthesis, characterization, biological activity and electrochemistry studies of iron(III) complex with curcumin-oxime ligand. Clinical and Experimental Pharmacology and Physiology, vol. 47, no. 11, pp. 1834–1842.
[45] Wilkonson, J. (2006). Iron chelation in the biological activity of curcumin. Free Radical Biology and Medicine, vol. 40, no. 7, pp. 1152–1160.
[46] Hussain, M. A. (2015). Comparative study on hematological changes in adult and aged rats after curcumin administration. Bulletin of Egyptian Society for Physiological Sciences, vol. 34, no. 3, pp. 357–366.
[47] Yadav, R. and Jain, G. C. (2010). Post-coital contraceptive efficacy of aqueous extract of Curcuma longa rhizome in female albino rats. Pharmacologyonline, vol. 1, pp. 507–517.
[48] Zaribaf, F., Entezari, M. H., Hassanzadeh, A., et al. (2014). Association between dietary iron, iron stores, and serum lipid profile in reproductive age women. Journal of Education and Health Promotion, vol. 3, p. 15.
[49] Mohammadi, E., Tamaddoni, A., Qujeq, D., et al. (2018). An investigation of the effects of curcumin on iron overload, hepcidin level, and liver function in β-thalassemia major patients: A double-blind randomized controlled clinical trial. Phytotherapy Research, vol. 32, no. 9, pp. 1828–1835.
[50] Sadeek, E. A. and El Razek, H. A. (2010). The chemo-protective effect of turmeric, chili, cloves and cardamom on correcting iron overload-induced liver injury, oxidative stress and serum lipid profile in rat models. Journal of American Science, vol. 6, no. 10, pp. 702–712.
[51] Lebda, M. A. (2014). Acute iron overload and potential chemotherapeutic effect of turmeric in rats. Indian Journal of Pure & Applied Biosciences, vol. 2, no. 2, pp. 86–94.
[52] EL-Maraghy, S. A., Rizk, S. M., and El-Sawalhi, S. S. (2009). Hepatoprotective potential of crocin and curcumin against iron overload-induced biochemical alterations in rat. African Journal of Biochemistry Research, vol. 3, no. 5, pp. 215–221.
[2] Özbolat, G. and Yegani, A. A. (2019). In vitro effects of iron chelation of curcumin Fe (III) complex. Cukurova Medical Journal, vol. 4, p. 3.
[3] Paul, B. T., Manz, D. H., Torti, F. M., et al. (2017). Mitochondria and iron: current questions. Expert Review of Hematology, vol. 10, no. 1, pp. 65–79.
[4] Özbolat, G., Yegani, A. A., and Tuli, A. (2018). Synthesis, characterization and electrochemistry studies of iron (III) complex with curcumin ligand. Clinical and Experimental Pharmacology and Physiology, vol. 45, no. 11, pp. 1221–1226.
[5] Ludwig, H., Evstatiev, R., Kornek, G., et al. (2015). Iron metabolism and iron supplementation in cancer patients. Wiener Klinische Wochenschrift, vol. 127, no. 23–24, pp. 907–919.
[6] Winter, W. E., Bazydlo, L. A., and Harris, N. S. (2014). The molecular biology of human iron metabolism. Laboratory Medicine, vol. 45, no. 2, pp. 92–102.
[7] Özbolat, G. and Tuli, A. (2018). Iron chelating ligand for iron overload diseases. Bratislava Medical Journal, vol. 119, no. 5, pp. 308–311.
[8] Kaplan, J. and Ward, D. M. (2013). The essential nature of iron usage and regulation. Current Biology, vol. 23, no. 15, pp. R642–R646.
[9] Yiase, S. G., Adejo, S. O., Gbertyo, A. J., et al. (2014). Synthesis, characterization and antimicrobial studies of salicylic acid complexes of some transition metals. IOSR Journal of Applied Chemistry, vol. 7, no. 4, pp. 4–10.
[10] Kontoghiorghe, C. N., Kolnagou, A., and Kontoghiorghes, G. J. (2015). Phytochelators intended for clinical use in iron overload, other diseases of iron imbalance and free radical pathology. Molecules, vol. 20, no. 11, pp. 20841–20872.
[11] Özbolat, G. and Yegani, A. A. (2020). Synthesis, characterization, biological activity and electrochemistry studies of iron(III) complex with curcumin-oxime ligand. CEPP – Clinical and Experimental Pharmacology and Physiology, vol. 47, no. 11, pp. 1834–1842.
[12] Potuckova, E., Hruskova, K., and Bures, J. (2014). Structure-activity relationships of novel salicylaldehyde isonicotinoyl hydrazone (SIH) analogs: iron chelation, anti-oxidant and cytotoxic properties. PLoS One, vol. 9, no. 11, p. e112059.
[13] Ehteram, H., Bavarsad, M. S., Mokhtari, M., et al. (2014). Prooxidant-antioxidant balance and hs-CRP in patients with beta-thalassemia major. Clinical Laboratory, vol. 60, no. 2, pp. 207–215.
[14] Kontoghiorghe, C. N. and Kontoghiorghes, G. J. (2016). New developments and controversies in iron metabolism and iron chelation therapy. World Journal of Methodology, vol. 6, no. 1, pp. 1–19.
[15] Liu, Z. D. and Hider, R. C. (2002). Design of clinically useful iron (III)-selective chelators. Medicinal Research Reviews, vol. 22, no. 1, pp. 26–64.
[16] Shander, A., Cappellini, M. D., and Goodnough, L. (2009). Iron overload and toxicity: the hidden risk of multiple blood transfusions. Vox Sanguinis, vol. 97, pp. 185–197.
[17] Porter, J. B. (2007). Concepts and goals in the management of transfusional iron overload. American Journal of Hematology, vol. 82, pp. 1136–1139.
[18] Buss, J. L., Torti, F. M., and Torti, S. V. (2003). The role of iron chelation in cancer therapy. Current Medicinal Chemistry, vol. 10, pp. 1021–1034.
[19] Tam, T. F., Leung-Toung, R., Li, W., et al. (2003). Iron chelator research: past, present and future. Current Medicinal Chemistry, vol. 10, no. 12, pp. 983–995.
[20] Liu, Z. D. and Hider, R. C. (2002). Design of clinically useful iron(III)-selective chelators. Medicinal Research Reviews, vol. 22, no. 1, pp. 26–64.
[21] Crisponi, G., Dean, A., Di Marco, V., et al. (2013). Different approaches to the study of chelating agents for iron and aluminium overload pathologies. Analytical and Bioanalytical Chemistry, vol. 405, no. 2–3, pp. 585–601.
[22] Ma, Y., Zhou, T., Kong, X., et al. (2012). Chelating agents for the treatment of systemic iron overload. Current Medicinal Chemistry, vol. 19, no. 17, p. 2816.
[23] Casu, C. and Rivella, S. (2014). Iron age: novel targets for iron overload. Hematology: the American Society of Hematology Education Program, vol. 2014, no. 1, pp. 216–221.
[24] Delea, T. E., Edelsberg, J., Sofrygin, O., et al. (2007). Consequences and costs of noncompliance with iron chelation therapy in patients with transfusion-dependent thalassemia: a literature review. Transfusion, vol. 47, no. 10, pp. 1919–1929.
[25] Mobarra, N., Shanaki, M., Ehteram, H., et al. (2016). A review on iron chelators in treatment of iron overload syndromes. International Journal of Hematology-Oncology and Stem Cell Research, vol. 10, no. 4, pp. 239–247.
[26] Porter, J. B. (2007). Concepts and goals in the management of transfusional iron overload. American Journal of Hematology, vol. 82, no. 12, pp. 1136–1139.
[27] Shah, N. R. (2017). Advances in iron chelation therapy: transitioning to a new oral formulation. Drugs in Context, vol. 6, p. 212502.
[28] Sheth, S. (2014). Iron chelation: an update. Current Opinion in Hematology, vol. 21, no. 3, pp. 179–185.
[29] Davis, B. A. and Porter, J. B. (2000). Long-term outcome of continuous 24-hour desferoxamine infusion via indwelling intravenous catheters in high-risk beta thalassemia. Blood, vol. 95, no. 4, pp. 1229–1236.
[30] Uygun, V. and Kurtoglu E. (2013). Iron-chelation therapy with oral chelators in patients with thalassemia major. Hematology, vol. 18, no. 1, pp. 50–55.
[31] Rockville, M. D. (2015). Ferriprox (deferiprone) Prescribing Information. Rockville, USA: ApoPharma USA Inc.
[32] Borgna-Pignatti, C., Cappellini, M. D., De Stefano, P., et al. (2006). Cardiac morbidity and mortality in deferoxamine- or deferiprone treated patients with thalassemia major. Blood, vol. 107, no. 9, pp. 3733–3737.
[33] Xia, S., Zhang, W., Huang, L., et al. (2013). Comparative efficacy and safety of deferoxamine, deferiprone and deferasirox on severe thalassemia: a meta-analysis of 16 randomized controlled trials. PLoS One, vol. 8, no. 12, p. e82662.
[34] Hejazi, S., Safari, O., Arjmand, R., et al. (2016). Effect of combined versus monotherapy with deferoxamine and deferiprone in iron overloaded thalassemia patients: a randomized clinical trial. International Journal of Pediatrics, vol. 4, no. 30, pp. 1959–1965.
[35] Caro J., Huybrechts, K. F., and Green, T. C. (2002). Estimates of the effect on hepatic iron of oral deferiprone compared with subcutaneous desferrioxamine for treatment of iron overload in thalassemia major: a systematic review. BMC Blood Disorders, vol. 2, no. 1, p. 4.
[36] Ejaz, M. S., Baloch, S., and Arif, F. (2015). Efficacy and adverse effects of oral chelating therapy (deferasirox) in multi-transfused Pakistani children with β-thalassemia major. Pakistan Journal of Medical Sciences, vol. 31, no. 3, pp. 621–625.
[37] Senol, S. F., Tiftik, E. C., Unal, S., et al. (2016). Quality of life, clinical effectiveness, and satisfaction in patients with beta thalassemia major and sickle cell anemia receiving deferasirox chelation therapy. Journal of Basic and Clinical Pharmacy, vol. 7, no. 2, pp. 49–59.
[38] Du, X.-X., Xu, H.-M., Jiang, H., et al. (2012). Curcumin protects nigral dopaminergic neurons by iron-chelation in the 6-hydroxydopamine rat model of Parkinson’s disease. Neuroscience Bulletin, vol. 28, no. 3, pp. 253–258.
[39] Messne, D. J., Sivam, G., and Kowdley, K. V. (2009). Curcumin reduces the toxic effects of iron loading in rat liver. Liver International, vol. 29, no. 1, pp. 63–72.
[40] Crisponi, G., Nurchi, V. M., and Zoroddu, M. A. (2014). Iron chelating agents for Iron overload diseases. Thalassemia Reports, vol. 4, no. 2.
[41] Erdincler, D. S., Seven, A., Inci, F., et al. (1997). Lipid peroxidation and antioxidant status in experimental animals: effects of aging and hypercholesterolemic diet. Clinica Chimica Acta, vol. 265, no. 1, pp. 77–84.
[42] Reardon, T. F. and Allen, D. G. (2009). Iron injections in mice increase skeletal muscle iron content, induce oxidative stress and reduce exercise performance. Experimental Physiology, vol. 94, no. 6, pp. 720–730.
[43] Merono, T., Gomez, L., Sorroche, P., et al. (2011). High risk of cardiovascular disease in iron overload patients. European Journal of Clinical Investigation, vol. 41, no. 5, pp. 479–486.
[44] Özbolat, G. and Yegani, A. A. (2020). Synthesis, characterization, biological activity and electrochemistry studies of iron(III) complex with curcumin-oxime ligand. Clinical and Experimental Pharmacology and Physiology, vol. 47, no. 11, pp. 1834–1842.
[45] Wilkonson, J. (2006). Iron chelation in the biological activity of curcumin. Free Radical Biology and Medicine, vol. 40, no. 7, pp. 1152–1160.
[46] Hussain, M. A. (2015). Comparative study on hematological changes in adult and aged rats after curcumin administration. Bulletin of Egyptian Society for Physiological Sciences, vol. 34, no. 3, pp. 357–366.
[47] Yadav, R. and Jain, G. C. (2010). Post-coital contraceptive efficacy of aqueous extract of Curcuma longa rhizome in female albino rats. Pharmacologyonline, vol. 1, pp. 507–517.
[48] Zaribaf, F., Entezari, M. H., Hassanzadeh, A., et al. (2014). Association between dietary iron, iron stores, and serum lipid profile in reproductive age women. Journal of Education and Health Promotion, vol. 3, p. 15.
[49] Mohammadi, E., Tamaddoni, A., Qujeq, D., et al. (2018). An investigation of the effects of curcumin on iron overload, hepcidin level, and liver function in β-thalassemia major patients: A double-blind randomized controlled clinical trial. Phytotherapy Research, vol. 32, no. 9, pp. 1828–1835.
[50] Sadeek, E. A. and El Razek, H. A. (2010). The chemo-protective effect of turmeric, chili, cloves and cardamom on correcting iron overload-induced liver injury, oxidative stress and serum lipid profile in rat models. Journal of American Science, vol. 6, no. 10, pp. 702–712.
[51] Lebda, M. A. (2014). Acute iron overload and potential chemotherapeutic effect of turmeric in rats. Indian Journal of Pure & Applied Biosciences, vol. 2, no. 2, pp. 86–94.
[52] EL-Maraghy, S. A., Rizk, S. M., and El-Sawalhi, S. S. (2009). Hepatoprotective potential of crocin and curcumin against iron overload-induced biochemical alterations in rat. African Journal of Biochemistry Research, vol. 3, no. 5, pp. 215–221.