Skip to main content
Log in

Influence of the Selected Antioxidants on the Stability of the Celsior Solution Used for Perfusion and Organ Preservation Purposes

  • Research Article
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

The purpose of the following research was to improve the original Celsior solution in order to obtain a higher degree of stability and effectiveness. The solution was modified by the addition of selected antioxidants such as vitamin C, cysteine, and fumaric acid in the following concentrations: 0.1, 0.3, and 0.5 mmol/l. The solution’s stability was estimated using an accelerated stability test based on changes in histidine concentrations in the solution using Pauly’s method for determining concentrations. Elevated temperatures, the factor accelerating substances’ decomposition reaction rate, were used in the tests. The research was conducted at four temperatures at intervals of 10°C: 60 ± 0.2°C, 70 ± 0.2°C, 80 ± 0.2°C, and 90 ± 0.2°C. It was stated that the studied substances’ decomposition occurred in accordance with the equation for first-order reactions. The function of the logarithmic concentration (log%C) over time was revealed to be rectilinear. This dependence was used to determine the kinetics of decomposition reaction rate parameters (the rate constant of decomposition k, activation energy E a, and frequency factor A). On the basis of these parameters, the stability of the modified solution was estimated at +5°C. The results obtained show that the proposed antioxidants have a significant effect on lengthening the Celsior solution’s stability. The best results were reached when combining two antioxidants: vitamin C and cysteine in 0.5 mmol/l concentrations. As a result, the Celsior solution’s stability was lengthened from 22 to 299 days, which is 13.5 times. Vitamin C at a concentration of 0.5 mmol/l increased the solution’s stability by 5.2 times (t 90 = 115 days), cysteine at a concentration of 0.5 mmol/l caused a 4.4 times stability increase (t 90 = 96 days), and fumaric acid at a concentration of 0.5 mmol/l extended the stability by 2.1 times (t 90 = 48 days) in relation to the original solution.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Budziński G, Cierpka L. Methods of storing organs for transplantation purposes. In: Smorg Z, Słomki R, Cierpka L, editors. Biotechnological and medical foundations of xenotransplantation. Poznan: Ośrodek Wydawnictw Naukowych; 2006. p. 279–90.

    Google Scholar 

  2. Kosieradzki M, Danielewicz R. Ischemic damage of organs and their storage. In: Rowiński W, Wałaszewski J, Pczka L, editors. Clinical transplantology. Warsaw: Wydawnictwo Lekarskie PZWL; 2004. p. 105–21.

    Google Scholar 

  3. Ryszka F, Dolińska B, Ostróżka-Cieślik A. Solutions for organs storage purposes and evaluation of their efficiency. In: Smorg Z, Słomski R, Cierpka L, editors. Biotechnological and medical foundations of xenotransplantation. Poznan: Ośrodek Wydawnictw Naukowych; 2006. p. 291–303.

    Google Scholar 

  4. Ryszka F, Ostróżka-Cieślik A, Dolińska B. Impact of solutions components for organs storage purposes on their stability and biochemical properties. Biotechnologia 2006;1(72):97–102.

    Google Scholar 

  5. Roberts RF, Nishanian GP, Carey JN, Sakamaki Y, Starnes VA, Barr ML. A comparison of the new preservation solution Celsior to EuroCollins and University of Wisconsin solutions in lung reperfusion injury. Transplantation 1999;67(1):152–5.

    Article  PubMed  CAS  Google Scholar 

  6. Xiong L, Legagneux J, Wassef M, Oubenaissa A, Detruit H, Mouas C, et al. Protective effects of Celsior in lung transplantation. J Heart Lung Transplant 1999;18:320–7.

    Article  PubMed  CAS  Google Scholar 

  7. Janßen H, Janßen PH, Broelsch CE. Celsior solution compared with University of Wisconsin solution (UW) and histidine–tryptophan–ketoglutarate solution (HTK) in the protection of human hepatocytes against ischemia–reperfusion injury. Transpl Int 2003;16:515–22.

    PubMed  Google Scholar 

  8. Howden BO, Jablonski P. Liver preservation: a comparison of Celsior to colloid-free University of Wisconsin solution. Transplantation 2000;70:1140–2.

    Article  PubMed  CAS  Google Scholar 

  9. Carrier M, Trudel S, Pelletier LC. Effect of Celsior and University of Wisconsin solutions on myocardial metabolism and function after warm ischemia. J Cardiovasc Surg (Torino). 1999;40(6):811–16.

    CAS  Google Scholar 

  10. Mohara J, Takahashi T, Oshima K, Aiba M, Yamagishi T, Takeyoshi I, et al. The effect of Celsior solution on 12-hour cardiac preservation in comparison with University of Wisconsin solution. J Cardiovasc Surg (Torino). 2001;42(2):187–92.

    CAS  Google Scholar 

  11. Abrahamse STL, Dinant S, Pfaffendorf M, Gulik TM. In vitro function of porcine carotid arteries preserved in UW, HTK and Celsior solutions. Fund Clin Pharmacol 2002;16(6):503–11.

    Article  CAS  Google Scholar 

  12. Włodek L. Oxygen reactive species in physiological and pathological conditions. Cellular antioxidant systems. Farm Pol 2004;9:404–18.

    Google Scholar 

  13. Southard JH, Den-Butter B, Marsh DC. The role of oxygen free radicals in organ preservation. Klin Wochenschr 1991;21:1073–6.

    Article  Google Scholar 

  14. Bilska A, Kryczyk A, Włodek L. The different aspects of the biological role of glutathione. Post Hig Med Dosw 2007;61:438–53.

    Google Scholar 

  15. Wu G, Fang YZ, Yang S, Pluton JR. Glutathione metabolism and its implications for health. J Nutr. 2004;134:489–92.

    PubMed  CAS  Google Scholar 

  16. Markuszewski L, Okoński P, Banach M, Wierzbiński P, Pietruszyński R. Role of oxidative stress and reactive oxygen species in pathogenesis of stunning myocardium. Glutathione as a substance which prevents stunning. Folia Cardiol. 2006;13(1):9–18.

    Google Scholar 

  17. Włodek L. Biothols in physiological and pathological conditions and in therapy. Krakow: Wydawnictwo Uniwersytetu Jagiellońskiego; 2003. p. 7–15.

    Google Scholar 

  18. Guz J, Dziaman T, Szpila A. Do antioxidant vitamins influence carcinogenesis process? Post Hig Med Dosw. 2007;61:185–98.

    Google Scholar 

  19. Konopacka M. Function of vitamin C in oxidant damages of DNA. Post Hig Med Dosw. 2004;58:343–8.

    Google Scholar 

  20. Sies H, Stahl W, Sundquist AR. Antioxidant functions of vitamins. Vitamins E and C, beta-carotene, and other carotenoids. Ann NY Acad Sci. 1992;669:7–20.

    Article  PubMed  CAS  Google Scholar 

  21. Padayatty SJ, Katz A, Wang Y, Eck P, Kwon O, Lee J, et al. Vitamin C as an antioxidant: evaluation of its role in disease prevention. J Am Coll Nutr. 2003;22:18–35.

    PubMed  CAS  Google Scholar 

  22. Sroka Z, Gamian A, Cisowski W. Low molecular antioxidant compounds of natural origin. Post Hig Med Dosw 2005;59:34–41.

    Google Scholar 

  23. Lloberas N, Torras J, Herrero-Fresneda I, Cruzado JM, Riera M, Hurtado I, Grinyo JM. Postischemic renal oxidative stress induces inflammatory response through PAF and oxidized phospholipids. Prevention by antioxidant treatment. FASEB J 2002;16:908–10.

    PubMed  CAS  Google Scholar 

  24. Deutsch JC. Ascorbic acid oxidation by hydrogen peroxide. Anal Biochem 1998;255:1–7.

    Article  PubMed  CAS  Google Scholar 

  25. Kulikowska-Karpińska E, Moniuszko-Jakoniuk J. The antioxidative barrier in the organism. Pol J Environ Stud 2004;13(1):5–13.

    Google Scholar 

  26. Ziemlański Ś, Wartanowicz M. Function of nutritional antioxidants in health and disease. Pediatr Współcz Gastroenterol Hepatol Żywienie Dziecka 1999;1:97–105.

    Google Scholar 

  27. Piekutowski K, Roszkowski K. Free oxygen radicals. Protective function of antioxidant vitamins in tumors prevention and treatment. Współcz Onkol 1999;4:143–4.

    Google Scholar 

  28. Laplante A, Vincent G, Poirier M, Rosiers C. Effects and metabolism of fumarate in the perfused rat heart; A 13C mass isotopomer study. Am J Physiol 1997;272:E74–82.

    PubMed  CAS  Google Scholar 

  29. Pearl JM, et al. Fumarate enriched blood cardioplegia results in complete functional recovery of immature myocardium. Ann Thorac Surg 1993;57:1636–41.

    Article  Google Scholar 

  30. Sangstat Medical Corporation; 1999. http://www.sangstat.com/docs/celsior_pl.pdf. Accessed June 22, 2004.

  31. Alexander RJ. A laboratory manual of analytical methods of protein chemistry. New York: Pergamon; 1970. p. 234–56.

    Google Scholar 

  32. Shi L, Schofield T. Pharmaceutical stability testing conference. Expert Opin Drug Saf 2004;3:153–8.

    Article  PubMed  Google Scholar 

  33. International Conference on Harmonization (ICH). Guidance for Industry. Q2B. Validation of Analytical Procedures: Methodology. 1996. Available at http://www.fda.gov/cder/guidance/index.htm. Accessed June 25, 2003.

  34. Truhlar DG, Kohen A. Convex Arrhenius plots and their interpretation. PNAS. 2001;98(3):848–51.

    Article  PubMed  CAS  Google Scholar 

  35. Joule JA, Smith GF. Chemistry of heterocyclic compounds. Warsaw: PWN; 1984. p. 43.

    Google Scholar 

  36. Stanosz M, Mach-Szczypiński J, Stanosz S. Biochemical and pharmacological aspects of histamine. Gin Prakt. 2005;86(5):37–42.

    Google Scholar 

  37. Tomasik P. Mechanism of organic reactions. Warsaw: PWN; 1998. p. 26.

    Google Scholar 

  38. Bartosz G. Second nature of oxygen. Warsaw: PWN; 1995. p. 27.

    Google Scholar 

  39. Ciszewska-Jędrasik M, Pertkiewicz M. Mixtures for perentenal nutrition purposes. Warsaw: PZWL; 2004. p. 12–27.

    Google Scholar 

  40. Dolińska B, Ryszka F, Ostróżka-Cieślik A. The effect of selected antioxidants on the kinetics of changes in the stability of an HTK Solution. A technical note. AAPS PharmSciTech 2006;7(2) Article 51.

Download references

Acknowledgments

This study was funded by the State Committee for Scientific Research, Warsaw, Poland (grant PBZ-KBN-048/PO5/2001).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Barbara Dolińska.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ostróżka-Cieślik, A., Dolińska, B. & Ryszka, F. Influence of the Selected Antioxidants on the Stability of the Celsior Solution Used for Perfusion and Organ Preservation Purposes. AAPS PharmSciTech 10, 468–475 (2009). https://doi.org/10.1208/s12249-009-9232-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1208/s12249-009-9232-3

Key words

Navigation