Effect of Polyhemoglobin and Synthetic Enzymes on Ischemic Cardiomyocytes
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Abstract
We studied the effect of a novel solution consisting of polyhemoglobin together with three synthetic enzymes (neocatalase, neosuperoxide dismutase, and neocarbonic anhydrase) on ischemic human cardiomyocytes. Polyhemoglobin alone showed minimal protective effects. The addition of the three synthetic enzymes to polyhemoglobin provided antioxidant protection, reduced Reactive Oxygen Species (ROS) levels, and improved cellular recovery. ROS production and mitochondrial function assays confirmed significant reductions in oxidative damage with the combined treatment. Apoptosis and necrosis detection showed improved cell survival, while cardiac troponin assays indicated reduced myocardial injury. The novel solution of polyhemoglobin with all three synthetic enzymes provided the best protection compared to polyhemoglobin alone or polyhemoglobin combined with only two neoenzymes (neoCatalase and neoSuperoxide Dismutase). This study highlights the potential of polyhemoglobin with the three synthetic enzymes for the next generation blood substitutes and organ preservation as it offers a novel approach to improving the outcomes of ischemic cardiomyocytes.
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1. Chang TMS, Bülow L, Jahr JS, Sakai H, Yang C. Nanobiotherapeutic based blood substitutes. Singapore: World Scientific Publishing Co. Pte. Ltd.; 2022;1042. Available from: https://www.worldscientific.com/worldscibooks/10.1142/12054#t=aboutBook
2. Chang TMS. Semipermeable microcapsules. Science. 1964;146:524–525. Available from: https://doi.org/10.1126/science.146.3643.524
3. Chang TMS. Therapeutic applications of polymeric artificial cells. Nat Rev Drug Discov. 2005;4:221–235. Available from: https://doi.org/10.1038/nrd1659
4. Chang TMS. ARTIFICIAL CELL evolves into nanomedicine, biotherapeutics, blood substitutes, and more. Artif Cells Nanomed Biotechnol. 2019;47(1):997–1013. Available from: https://doi.org/10.1080/21691401.2019.1577885
5. Chang TMS. Monograph on ‘ARTIFICIAL CELLS: biotechnology, nanotechnology, blood substitutes, regenerative medicine, bioencapsulation, cell/stem cell therapy’. Singapore/London: World Scientific Publisher/Imperial College Press. 2023;435. Available from: https://doi.org/10.3389/fmedt.2023.1306419
6. Chang TMS. Stabilization of enzyme by microencapsulation with a concentrated protein solution or by crosslinking with glutaraldehyde. Biochem Biophys Res Commun. 1971;44:1531–1533. Available from: https://doi.org/10.1016/s0006-291x(71)80260-7
7. Jahr J, Tseng K, Brown AP, Dubé GP. Hemoglobin-glutamer 250 (Bovine) [HBOC-201, Hemopure®] Clinical Use in South Africa and Comprehensive Review of Cardiac Outcomes and Risk/Benefit in Peer-Reviewed, Indexed Studies in Humans and Animal Models. In: Chang TMS, editor. Nanobiotherapeutic based blood substitutes. Singapore: World Scientific Publishing Co. Pte. Ltd.; 2022;207–247. Available from: http://dx.doi.org/10.1142/9789811228698_0008
8. Moore EE, Moore FA, Fabian TC, Bernard AC, Fulda GJ, Hoyt DB, et al. Human polymerized hemoglobin for the treatment of hemorrhagic shock when blood is unavailable: The USA multicenter trial. J Am Coll Surg. 2009;208(1):1–13. Available from: https://doi.org/10.1016/j.jamcollsurg.2008.09.023
9. Natanson C, Kern SJ, Lurie P, Banks SM, Wolfe SM. Cell-free hemoglobin-based blood substitutes and risk of myocardial infarction and death: a meta-analysis. JAMA. 2008;299(19):2304–2312. Available from: https://doi.org/10.1001/jama.299.19.jrv80007
10. Bian Y, Chang TMS. A novel nanobiotherapeutic poly-[hemoglobin-superoxide dismutase-catalase-carbonic anhydrase] with no cardiac toxicity for the resuscitation of a rat model with 90 minutes of sustained severe hemorrhagic shock with loss of 2/3 blood volume. Artif Cells Nanomed Biotechnol. 2015;43(1):1–9. Available from: https://doi.org/10.3109/21691401.2014.964554
11. Bian Y, Chang TMS. Nanobiotechnological basis of an oxygen carrier with enhanced carbonic anhydrase for CO2 transport and enhanced catalase and superoxide dismutase for antioxidant function. Front Bioeng Biotechnol. 2023;11:1188399. Available from: https://doi.org/10.3389/fbioe.2023.1188399
12. Hoq M, Chang TMS. Preliminary feasibility study using a solution of synthetic enzymes to replace the natural enzymes in polyhemoglobin-catalase-superoxide dismutase-carbonic anhydrase: effect on warm ischemic hepatocyte cell culture. Front Bioeng Biotechnol. 2023;11:1231384. Available from: https://doi.org/10.3389/fbioe.2023.1231384
13. Hoq M, Chang TMS. Next-generation preservation solution using synthetic enzymes. Sci Rep. 2024;14:23104. Available from: https://www.nature.com/articles/s41598-024-73862-2
14. Tronstad C, Pischke SE, Holhjem L, Tønnessen TI, Martinsen OG, Grimnes S. Early detection of cardiac ischemia using a conductometric PCO2 sensor: Real-time drift correction and parameterization. Physiol Meas. 2010;31:1241–1255. Available from: https://doi.org/10.1088/0967-3334/31/9/013
15. Liu J. Zinc-based deep eutectic solvent – an efficient carbonic anhydrase mimic for CO2 hydration and conversion. Nat Commun. 2021;12(1):1–11.
16. Chen G, Chang TMS. Dual effects include antioxidant and pro-oxidation of ascorbic acid on the redox properties of bovine hemoglobin. Artif Cells Nanomed Biotechnol. 2018;46(sup2):983–992. Available from: https://doi.org/10.1080/21691401.2018.1476374