Influence of the Selected Antioxidants on the Stability of the Celsior Solution Used for Perfusion and Organ Preservation Purposes
- 182 Downloads
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.
Key wordsaccelerated stability test antioxidants ascorbic acid Celsior cysteine fumaric acid
This study was funded by the State Committee for Scientific Research, Warsaw, Poland (grant PBZ-KBN-048/PO5/2001).
- 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
- 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.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.Google Scholar
- 12.Włodek L. Oxygen reactive species in physiological and pathological conditions. Cellular antioxidant systems. Farm Pol 2004;9:404–18.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
- 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
- 22.Sroka Z, Gamian A, Cisowski W. Low molecular antioxidant compounds of natural origin. Post Hig Med Dosw 2005;59:34–41.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
- 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
- 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.
- 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.Google Scholar