Sickle Cell Disease Pain and Zinc, Any Link? A Case-Control Study among Patients With Sickle Cell Disease In Korle-Bu

Grace Ababio; Lawrence Ababio Boateng; Eugenia V. Asare; Robert Reeks; Anthony Dongdem

doi:10.18535/ijsrm/v12i08.mp01

Abstract

Background: Over some few decades, markers of pain have been studied, of which some trace elements are of no exception. Yet, there is paucity of data on trace elements in SCD pain. Here, zinc levels and its relation to SCD vaso-occlusive pain was shown.

Aim: To determine [zinc] and its relation to pain in sickle cell disease patients.

Methodology: The case-control study was located at the Ghana Institute of Clinical Genetics (sickle cell clinic). After obtaining ethical clearance from College of Health Sciences (CHS-Et/M.1-P5.12/2023-2024), a validated pain assessment questionnaires were used for data collection. Ten (10) mls of blood was collected, six (6) mL was placed in a serum separating tube (SST) for the determination of zinc and four (4) mL into EDTA tube for full blood count and Hemoglobinopathy on cellulose acetate electrophoresis. The data analysis was done using the Statistical Package for the Social Science (SPSS) version 21 and Microsoft Excel 2016.

Results: Average zinc levels for the entire SCD VOC, was 2.569±1.073(39) and this was relatively low during comparison. [Zn] in SCD subjects who consume alcohol yielded p – value of 0.0001 while in patients experiencing VOC had a p-value = 0.000. The odds ratio for zinc exposure seemed to have protective effect on sickle cell disease either in steady state or vaso-occlusive state. [Zn] stratifications also related statistically to blood pressure readings, SCD pain, hemoglobin, red blood cells, white blood cells, platelets and body mass index. Conclusion: The average [Zn] in SCD individuals experiencing VOC was relatively low (p-value = 0.000

Keywords

zinctrace elementsSickle cell diseaseatomic absorption spectroscopy

References

Ballas SK, Darbari DS. Review/overview of pain in sickle cell disease. Complementary Therapies in Medicine. 2020;49:102327.Google Scholar ↗
Saraf SL, Molokie RE, Nouraie M, Sable CA, Luchtman-Jones L, Ensing GJ, Campbell AD, Rana SR, Niu XM, Machado RF, Gladwin MT. Differences in the clinical and genotypic presentation of sickle cell disease around the world. Paediatric respiratory reviews. 2014;15(1):4-12.Google Scholar ↗
Asare EV, Wilson I, Benneh-Akwasi Kuma AA, Dei-Adomakoh Y, Sey F, Olayemi E. Burden of sickle cell disease in Ghana: The Korle‐Bu experience. Advances in hematology. 2018;2018(1):6161270.Google Scholar ↗
Ampomah MA, Drake JA, Anum A, Amponsah B, Dei‐Adomakoh Y, Anie K, Mate‐Kole CC, Jonassaint CR, Kirkham FJ. A case‐control and seven‐year longitudinal neurocognitive study of adults with sickle cell disease in Ghana. British Journal of Haematology. 2022;199(3):411-26.Google Scholar ↗
de Oliveira Fernandes Miranda CT, Vermeulen-Serpa KM, Cabanas Pedro AC, Brandao-Neto J, de Lima Vale SH, Figueiredo MS. Zinc in sickle cell disease: A narrative review. Journal Of Trace Elements In Medicine And Biology. 2022;72:126980Google Scholar ↗
Swe KM, Abas AB, Bhardwaj A, Barua A, Nair NS. Zinc supplements for treating thalassaemia and sickle cell disease. Cochrane Database of Systematic Reviews. 2013(6).Google Scholar ↗
Prasad AS. Impact of the discovery of human zinc deficiency on health. Journal of trace elements in medicine and biology. 2014;28(4):357-63.Google Scholar ↗
Prasad AS. Discovery of zinc for human health and biomarkers of zinc deficiency. In Molecular, genetic, and nutritional aspects of major and trace minerals. 2017 (pp. 241-260). Academic Press.Google Scholar ↗
Temiye EO, Duke ES, Owolabi MA, Renner JK. Relationship between painful crisis and serum zinc level in children with sickle cell anaemia. Anemia. 2011;2011(1):698586.Google Scholar ↗
Abrams SA. Zinc deficiency and supplementation in children. Motil KJ, editor. 2020. https://medilib.ir/uptodate/show/5354Google Scholar ↗
Sharaf BK, Atrushi AM. Role of sickling crisis with serum zinc in children with sickle cell anemia. AMJ (Advanced Medical Journal). 2022;6(2):51-9.Google Scholar ↗
Namazzi R, Opoka R, Conroy AL, Datta D, Tagoola A, Bond C, Goings MJ, Ryu MS, Cusick SE, Krebs NF, Jang JH. Zinc for infection prevention in children with sickle cell anemia: a randomized double-blind placebo-controlled trial. Blood Advances. 2023 ;7(13):3023-31.Google Scholar ↗
Ugwu NI, Okike C, Ugwu CN, Ezeonu CT, Iyare FE, Alo C. Assessment of zinc level and its relationship with some hematological parameters among patients with sickle cell anemia in Abakaliki, Nigeria. Nigerian Journal of Medicine. 2021;30(1):55-9.Google Scholar ↗
Liu E, Pimpin L, Shulkin M, Kranz S, Duggan CP, Mozaffarian D, Fawzi WW. Effect of zinc supplementation on growth outcomes in children under 5 years of age. Nutrients. 2018;10(3):377.Google Scholar ↗
Ballas SK. More definitions in sickle cell disease: steady state v base line data. American journal of hematology. 2012;87(3):338.Google Scholar ↗
Nozaki C, Vergnano AM, Filliol D, Ouagazzal AM, Le Goff A, Carvalho S, Reiss D, Gaveriaux-Ruff C, Neyton J, Paoletti P, Kieffer BL. Zinc alleviates pain through high-affinity binding to the NMDA receptor NR2A subunit. Nature neuroscience. 2011;14(8):1017-22.Google Scholar ↗
Lima CK, Sisnande T, Silva RV, Silva VD, Amaral JJ, Ochs SM, Santos BL, Miranda AL, Lima LM. Zinc deficiency disrupts pain signaling promoting nociceptive but not inflammatory pain in mice. Anais da Academia Brasileira de Ciências. 2023;95(suppl 1):e20220914.Google Scholar ↗
Darbari DS, Ballas SK, Clauw DJ. Thinking beyond sickling to better understand pain in sickle cell disease. European journal of haematology. 2014;93(2):89-95.Google Scholar ↗
Tuerk MJ, Fazel N. Zinc deficiency. Current opinion in gastroenterology. 2009;25(2):136-43.Google Scholar ↗
Kloubert V, Wessels I, Wolf J, Blaabjerg K, Janssens V, Hapala J, Wagner W, Rink L. Zinc deficiency leads to reduced interleukin-2 production by active gene silencing due to enhanced CREMα expression in T cells. Clinical nutrition. 2021;40(5):3263-78.Google Scholar ↗
Yokokawa H, Fukuda H, Saita M, Miyagami T, Takahashi Y, Hisaoka T, Naito T. Serum zinc concentrations and characteristics of zinc deficiency/marginal deficiency among Japanese subjects. Journal of General and Family Medicine. 2020;21(6):248-55Google Scholar ↗
Nader E, Romana M, Connes P. The red blood cell—inflammation vicious circle in sickle cell disease. Frontiers in immunology. 2020;11:454.Google Scholar ↗
Gladwin MT, Kanias T, Kim-Shapiro DB. Hemolysis and cell-free hemoglobin drive an intrinsic mechanism for human disease. The Journal of clinical investigation. 2012;122(4):1205-8.Google Scholar ↗
Alayash AI. Hemoglobin-based blood substitutes and the treatment of sickle cell disease: more harm than help? Biomolecules. 2017;7(1):2.Google Scholar ↗
Ansari J, Gavins FN. Ischemia-reperfusion injury in sickle cell disease: from basics to therapeutics. The American Journal of Pathology. 2019;189(4):706-18.Google Scholar ↗
Zhang D, Xu C, Manwani D, Frenette PS. Neutrophils, platelets, and inflammatory pathways at the nexus of sickle cell disease pathophysiology. Blood, The Journal of the American Society of Hematology. 2016;127(7):801-9.Google Scholar ↗
Falih Neamah N, Naaeem Khudair AR, Al-Jadaan SA. In Vitro and in Vivo Measurements of ROS Scavenging Activity and White Blood Cells Activity by Chemiluminescence of a New Selena-Diazole Derivative Compare to Dipyrone Activity. In Journal of Physics Conference Series 2021;1818(1):012060.Google Scholar ↗
Bandeira IC, Rocha LB, Barbosa MC, Elias DB, Querioz JA, Freitas MV, Gonçalves RP. Chronic inflammatory state in sickle cell anemia patients is associated with HBB* S haplotype. Cytokine. 2014;65(2):217-21.Google Scholar ↗
Biswal S, Rizwan H, Pal S, Sabnam S, Parida P, Pal A. Oxidative stress, antioxidant capacity, biomolecule damage, and inflammation symptoms of sickle cell disease in children. Hematology. 2019;24(1):1-9.Google Scholar ↗
Xu Y, Li A, Li X, Deng X, Gao XJ. Zinc deficiency induces inflammation and apoptosis via oxidative stress in the kidneys of mice. Biological Trace Element Research. 2023;201(2):739-50.Google Scholar ↗
Prasad AS, Bao B. Molecular mechanisms of zinc as a pro-antioxidant mediator: clinical therapeutic implications. Antioxidants. 2019;8(6):164.Google Scholar ↗
Del Favero G, Hohenbichler J, Mayer RM, Rychlik M, Marko D. Mycotoxin altertoxin II induces lipid peroxidation connecting mitochondrial stress response to NF-κB inhibition in THP-1 macrophages. Chemical Research in Toxicology. 2020;33(2):492-504.Google Scholar ↗
Marreiro DD, Cruz KJ, Morais JB, Beserra JB, Severo JS, De Oliveira AR. Zinc and oxidative stress: current mechanisms. Antioxidants. 2017;6(2):24.Google Scholar ↗
Overbeck S, Rink L, Haase H. Modulating the immune response by oral zinc supplementation: a single approach for multiple diseases. Archivum immunologiae et therapiae experimentalis. 2008;56:15-30.Google Scholar ↗
Moheeb H, Wali YA, El‐Sayed MS. Physical fitness indices and anthropometrics profiles in schoolchildren with sickle cell trait/disease. American journal of hematology. 2007;82(2):91-7.Google Scholar ↗

[refR-1] Ballas SK, Darbari DS. Review/overview of pain in sickle cell disease. Complementary Therapies in Medicine. 2020;49:102327.Google Scholar ↗

[refR-2] Saraf SL, Molokie RE, Nouraie M, Sable CA, Luchtman-Jones L, Ensing GJ, Campbell AD, Rana SR, Niu XM, Machado RF, Gladwin MT. Differences in the clinical and genotypic presentation of sickle cell disease around the world. Paediatric respiratory reviews. 2014;15(1):4-12.Google Scholar ↗

[refR-3] Asare EV, Wilson I, Benneh-Akwasi Kuma AA, Dei-Adomakoh Y, Sey F, Olayemi E. Burden of sickle cell disease in Ghana: The Korle‐Bu experience. Advances in hematology. 2018;2018(1):6161270.Google Scholar ↗

[refR-4] Ampomah MA, Drake JA, Anum A, Amponsah B, Dei‐Adomakoh Y, Anie K, Mate‐Kole CC, Jonassaint CR, Kirkham FJ. A case‐control and seven‐year longitudinal neurocognitive study of adults with sickle cell disease in Ghana. British Journal of Haematology. 2022;199(3):411-26.Google Scholar ↗

[refR-5] de Oliveira Fernandes Miranda CT, Vermeulen-Serpa KM, Cabanas Pedro AC, Brandao-Neto J, de Lima Vale SH, Figueiredo MS. Zinc in sickle cell disease: A narrative review. Journal Of Trace Elements In Medicine And Biology. 2022;72:126980Google Scholar ↗

[refR-6] Swe KM, Abas AB, Bhardwaj A, Barua A, Nair NS. Zinc supplements for treating thalassaemia and sickle cell disease. Cochrane Database of Systematic Reviews. 2013(6).Google Scholar ↗

[refR-7] Prasad AS. Impact of the discovery of human zinc deficiency on health. Journal of trace elements in medicine and biology. 2014;28(4):357-63.Google Scholar ↗

[refR-8] Prasad AS. Discovery of zinc for human health and biomarkers of zinc deficiency. In Molecular, genetic, and nutritional aspects of major and trace minerals. 2017 (pp. 241-260). Academic Press.Google Scholar ↗

[refR-9] Temiye EO, Duke ES, Owolabi MA, Renner JK. Relationship between painful crisis and serum zinc level in children with sickle cell anaemia. Anemia. 2011;2011(1):698586.Google Scholar ↗

[refR-10] Abrams SA. Zinc deficiency and supplementation in children. Motil KJ, editor. 2020. https://medilib.ir/uptodate/show/5354Google Scholar ↗

[refR-11] Sharaf BK, Atrushi AM. Role of sickling crisis with serum zinc in children with sickle cell anemia. AMJ (Advanced Medical Journal). 2022;6(2):51-9.Google Scholar ↗

[refR-12] Namazzi R, Opoka R, Conroy AL, Datta D, Tagoola A, Bond C, Goings MJ, Ryu MS, Cusick SE, Krebs NF, Jang JH. Zinc for infection prevention in children with sickle cell anemia: a randomized double-blind placebo-controlled trial. Blood Advances. 2023 ;7(13):3023-31.Google Scholar ↗

[refR-13] Ugwu NI, Okike C, Ugwu CN, Ezeonu CT, Iyare FE, Alo C. Assessment of zinc level and its relationship with some hematological parameters among patients with sickle cell anemia in Abakaliki, Nigeria. Nigerian Journal of Medicine. 2021;30(1):55-9.Google Scholar ↗

[refR-14] Liu E, Pimpin L, Shulkin M, Kranz S, Duggan CP, Mozaffarian D, Fawzi WW. Effect of zinc supplementation on growth outcomes in children under 5 years of age. Nutrients. 2018;10(3):377.Google Scholar ↗

[refR-15] Ballas SK. More definitions in sickle cell disease: steady state v base line data. American journal of hematology. 2012;87(3):338.Google Scholar ↗

[refR-16] Nozaki C, Vergnano AM, Filliol D, Ouagazzal AM, Le Goff A, Carvalho S, Reiss D, Gaveriaux-Ruff C, Neyton J, Paoletti P, Kieffer BL. Zinc alleviates pain through high-affinity binding to the NMDA receptor NR2A subunit. Nature neuroscience. 2011;14(8):1017-22.Google Scholar ↗

[refR-17] Lima CK, Sisnande T, Silva RV, Silva VD, Amaral JJ, Ochs SM, Santos BL, Miranda AL, Lima LM. Zinc deficiency disrupts pain signaling promoting nociceptive but not inflammatory pain in mice. Anais da Academia Brasileira de Ciências. 2023;95(suppl 1):e20220914.Google Scholar ↗

[refR-18] Darbari DS, Ballas SK, Clauw DJ. Thinking beyond sickling to better understand pain in sickle cell disease. European journal of haematology. 2014;93(2):89-95.Google Scholar ↗

[refR-19] Tuerk MJ, Fazel N. Zinc deficiency. Current opinion in gastroenterology. 2009;25(2):136-43.Google Scholar ↗

[refR-20] Kloubert V, Wessels I, Wolf J, Blaabjerg K, Janssens V, Hapala J, Wagner W, Rink L. Zinc deficiency leads to reduced interleukin-2 production by active gene silencing due to enhanced CREMα expression in T cells. Clinical nutrition. 2021;40(5):3263-78.Google Scholar ↗

[refR-21] Yokokawa H, Fukuda H, Saita M, Miyagami T, Takahashi Y, Hisaoka T, Naito T. Serum zinc concentrations and characteristics of zinc deficiency/marginal deficiency among Japanese subjects. Journal of General and Family Medicine. 2020;21(6):248-55Google Scholar ↗

[refR-22] Nader E, Romana M, Connes P. The red blood cell—inflammation vicious circle in sickle cell disease. Frontiers in immunology. 2020;11:454.Google Scholar ↗

[refR-23] Gladwin MT, Kanias T, Kim-Shapiro DB. Hemolysis and cell-free hemoglobin drive an intrinsic mechanism for human disease. The Journal of clinical investigation. 2012;122(4):1205-8.Google Scholar ↗

[refR-24] Alayash AI. Hemoglobin-based blood substitutes and the treatment of sickle cell disease: more harm than help? Biomolecules. 2017;7(1):2.Google Scholar ↗

[refR-25] Ansari J, Gavins FN. Ischemia-reperfusion injury in sickle cell disease: from basics to therapeutics. The American Journal of Pathology. 2019;189(4):706-18.Google Scholar ↗

[refR-26] Zhang D, Xu C, Manwani D, Frenette PS. Neutrophils, platelets, and inflammatory pathways at the nexus of sickle cell disease pathophysiology. Blood, The Journal of the American Society of Hematology. 2016;127(7):801-9.Google Scholar ↗

[refR-27] Falih Neamah N, Naaeem Khudair AR, Al-Jadaan SA. In Vitro and in Vivo Measurements of ROS Scavenging Activity and White Blood Cells Activity by Chemiluminescence of a New Selena-Diazole Derivative Compare to Dipyrone Activity. In Journal of Physics Conference Series 2021;1818(1):012060.Google Scholar ↗

[refR-28] Bandeira IC, Rocha LB, Barbosa MC, Elias DB, Querioz JA, Freitas MV, Gonçalves RP. Chronic inflammatory state in sickle cell anemia patients is associated with HBB* S haplotype. Cytokine. 2014;65(2):217-21.Google Scholar ↗

[refR-29] Biswal S, Rizwan H, Pal S, Sabnam S, Parida P, Pal A. Oxidative stress, antioxidant capacity, biomolecule damage, and inflammation symptoms of sickle cell disease in children. Hematology. 2019;24(1):1-9.Google Scholar ↗

[refR-30] Xu Y, Li A, Li X, Deng X, Gao XJ. Zinc deficiency induces inflammation and apoptosis via oxidative stress in the kidneys of mice. Biological Trace Element Research. 2023;201(2):739-50.Google Scholar ↗

[refR-31] Prasad AS, Bao B. Molecular mechanisms of zinc as a pro-antioxidant mediator: clinical therapeutic implications. Antioxidants. 2019;8(6):164.Google Scholar ↗

[refR-32] Del Favero G, Hohenbichler J, Mayer RM, Rychlik M, Marko D. Mycotoxin altertoxin II induces lipid peroxidation connecting mitochondrial stress response to NF-κB inhibition in THP-1 macrophages. Chemical Research in Toxicology. 2020;33(2):492-504.Google Scholar ↗

[refR-33] Marreiro DD, Cruz KJ, Morais JB, Beserra JB, Severo JS, De Oliveira AR. Zinc and oxidative stress: current mechanisms. Antioxidants. 2017;6(2):24.Google Scholar ↗

[refR-34] Overbeck S, Rink L, Haase H. Modulating the immune response by oral zinc supplementation: a single approach for multiple diseases. Archivum immunologiae et therapiae experimentalis. 2008;56:15-30.Google Scholar ↗

[refR-35] Moheeb H, Wali YA, El‐Sayed MS. Physical fitness indices and anthropometrics profiles in schoolchildren with sickle cell trait/disease. American journal of hematology. 2007;82(2):91-7.Google Scholar ↗