Effects of uremic solutes on reactive oxygen species in vitro model systems as a possibility of support the renal function management

BMC Nephrology

Iguatemy L Brunetti¹  Amanda M Baviera¹  Olga MMF Oliveira²  Renata S Brotto¹  Carlos A Arcaro¹  Vânia O Gutierres¹  Juliana FA Castro²  Renata P Assis¹ 

[1] Department of Clinical Analysis, School of Pharmaceutical Sciences, São Paulo State University - UNESP, Rua Expedicionários do Brasil 1621, Araraquara CEP 14801-902, São Paulo, Brazil;Department of Biochemistry and Technological Chemistry, Institute of Chemistry, São Paulo State University - UNESP, Rua Prof. Francisco Degni 55, Araraquara CEP 14800-900, São Paulo, Brazil

关键词: IC50 as clinical chemistry tool;    Uremic solutes;    Oxidative stress;    Hemodialysis;    Chronic kidney disease;   

Others  :  1170983
DOI  :  10.1186/s12882-015-0029-1

 received in 2014-07-18, accepted in 2015-03-06,  发布年份 2015

【 摘 要 】

Background

In view of the prevalence of oxidative stress in chronic kidney disease (CKD) patients, the loss of low-molecular-weight biomolecules by hemodialysis and the antioxidant potential of some uremic solutes that accumulate in CKD, we used in vitro model systems to test the antioxidant potential of the following uremic solutes: uric acid, hippuric acid, p-cresol, phenol, methylguanidine, L-arginine, L-tyrosine, creatinine and urea.

Methods

The in vitro antioxidant efficiencies of the uremic solutes, isolated or in mixtures, were tested with the following assays: i) ABTS radical cation decolorization assay; ii) hypochlorous acid (HOCl/OCl⁻) scavenging activity; iii) superoxide anion radical (O₂^•-) scavenging activity; iv) crocin bleaching assay (capture of peroxyl radical, ROO^•); v) hydrogen peroxide (H₂O₂) scavenging activity.

Results

Four of the tested uremic solutes (p-cresol, phenol, L-tyrosine, uric acid) were effective antioxidants and their IC₅₀ were found in three model systems: ABTS^•+, HOCl/OCl⁻ and crocin bleaching assay. In the 4-solutes mixtures, each one of the solute captured 12.5% for the IC₅₀ of the mixture to ABTS^•+ or HOCl/OCl⁻, exhibiting a virtually exact additive effect. In the 2-solutes mixtures, for ROO^• capture, it was observed the need of more mass of uremic solutes to reach an IC₅₀ value that was higher than the projected IC₅₀, obtained from the IC₅₀ of single solutes (25% of each, in the binary mixtures) in the same assay. In model systems for O₂^•- and H₂O₂, none of the uremic solutes showed scavenging activity.

Conclusions

The use of the IC₅₀ as an analytical tool to prepare and analyze mixtures allows the determination of their scavenging capacities and may be useful for the assessment of the antioxidant status of biological samples under conditions of altered levels of the endogenous antioxidant network and/or in the employment and monitoring of exogenous antioxidant therapy.

【 授权许可】

   
2015 Assis et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】

• [1]Meenakshi Sundaram SP, Nagarajan S, Devi AJM: Chronic kidney disease—effect of oxidative stress. Chin J Biol 2014, 2014:1-6.
• [2]Small DM, Coombes JS, Bennett N, Johnson DW, Gobe GC: Oxidative stress, anti-oxidant therapies and chronic kidney disease. Nephrol 2012, 17:311-21.
• [3]Massy ZA, Stenvinkel P, Drueke TB: The role of oxidative stress in chronic kidney disease. Semin Dial 2009, 22:405-8.
• [4]Malyszko J: Mechanism of endothelial dysfunction in chronic kidney disease. Clin Chim Acta 2010, 411:1412-20.
• [5]Satoh M: Endothelial dysfunction as an underlying pathophysiological condition of chronic kidney disease. Clin Exp Nephrol 2012, 16:518-21.
• [6]Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY: Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 2004, 23:1296-305.
• [7]Schiffrin EL, Lipman ML, Mann JF: Chronic kidney disease: effects on the cardiovascular system. Circulation 2007, 116:85-97.
• [8]Vanholder R, Baurmeister U, Brunet P, Cohen G, Glorieux G, Jankowski J, et al.: A bench to beside view of uremic toxins. J Am Soc Nephrol 2008, 19:863-70.
• [9]Himmelfarb J, Ikizler TA: Hemodialysis. N Engl J Med 2010, 363:1833-45.
• [10]Kadkhodaee M, Hemmati M, Zahmatkesh M, Ghaznavi R, Mirershadi F, Mahdavi Mazde M, et al.: Assessment of plasma antioxidant status in hemodialysis patients. Ther Apher Dial 2008, 12:147-51.
• [11]Wratten ML, Galaris D, Tetta C, Sevanian A: Evolution of oxidative stress and inflammation during hemodialysis and their contribution to cardiovascular disease. Antioxid Redox Signal 2002, 4:935-44.
• [12]Glorieux G, Neirynck N, Veys N, Vanholder R: Dialysis water and fluid purity: more than endotoxin. Nephrol Dial Transplant 2012, 27:4010-21.
• [13]Chen MF, Chang CL, Liou SY: Increase in resting levels of superoxide anion in the whole blood of uremic patients on chronic hemodialysis. Blood Purif 1998, 16:290-300.
• [14]Ujhelyi L, Balla G, Jeney V, Varga Z, Nagy E, Vercellotti GM, et al.: Hemodialysis reduces inhibitory effect of plasma ultrafiltrate on LDL oxidation and subsequent endothelial reactions. Kidney Int 2006, 69:144-51.
• [15]Vanholder R, Van Laecke S, Glorieux G: What is new in uremic toxicity? Pediatr Nephrol 2008, 23:1211-21.
• [16]Mayer B, Zitta S, Greilberger J, Holzer H, Reibnegger G, Hermetter A, et al.: Effect of hemodialysis on the antioxidative properties of serum. Bioch Biophys Acta 2003, 1638:267-72.
• [17]Chen T, Liou S, Chang Y: Chemiluminescent analysis of plasma antioxidant capacity in uremic patients undergoing hemodialysis. Ren Fail 2008, 30:843-7.
• [18]Gerardi GM, Usberti M, Martini G, Albertini A, Sugherini L, Pompella A, et al.: Plasma total antioxidant capacity in hemodialyzed patients and its relationships to other biomarkers of oxidative stress and lipid peroxidation. Clin Chem 2002, 40:104-10.
• [19]Oowada S, Endo N, Kameya H, Shimmei M, Kotake Y: Multiple free-radical scavenging capacity in serum. J Clin Biochem Nutr 2012, 51:117-21.
• [20]Cao G, Prior RL: Comparison of different analytical methods for assessing total antioxidant capacity of human serum. Clin Chem 1998, 44:1309-15.
• [21]Halliwell B, Gutteridge JMC: The chemistry of free radicals and related ‘reactive species’. In Free radicals in biology and medicine. Edited by Halliwell B, Gutteridge JMC. Oxford, New York; 2010:30-78.
• [22]Re R, Pellegrini N, Proteggente A, Pannala A, Yang M, Rice-Evans C: Antioxidant activity applying improved ABTS radical cation decolorization assay. Free Rad Biol Med 1999, 26:1231-7.
• [23]Kakkar P, Das B, Viswanayhan PN: A modified spectrophotometric assay of superoxide dismutase. J Biochem Biophys 1984, 21:130-2.
• [24]Hazra B, Biswas S, Mandal N: Antioxidant and free radical scavenging activity of Spondias pinnata. BMC Complement Altern Med 2008, 8:1-10. BioMed Central Full Text
• [25]Kettle AJ, Winterbourn CC: Assays for the chlorination activity of myeloperoxidase. Methods Enzymol 1994, 233:233:502-12.
• [26]Dypbukt JM, Bishop C, Brooks WM, Thong B, Eriksson H, Kettle AJ: A sensitive and selective assay for chloramine production by myeloperoxidase. Free Rad Biol Med 2005, 39:1468-77.
• [27]Zgliczynski JM, Stelmaszynska T, Domanska J, Ostrowski W: Chloramines as intermediates of oxidation reaction of amino acids by myeloperoxidase. Biochem Biophys Acta 1971, 235:419-24.
• [28]Tubaro F, Ghiselli A, Rapuzzi P, Maiorino M, Ursini F: Analysis of plasma antioxidant capacity by competition kinetics. Free Rad Biol Med 1998, 24:1228-34.
• [29]Thomas EL, Grisham MB, Jefferson MM: Preparation and characterization of chloramines. Methods Enzymol 1986, 132:569-85.
• [30]Ching T, Jong J, Bast A: A method for screening hypochlorous acid scavengers by inhibition of the oxidation of 5-thio-2-nitrobenzoic acid: application to antiasthmatic drugs. Anal Biochem 1994, 218:377-81.
• [31]Ellman GL: Tissue sulfhydryl groups. Arch Biochem Biophys 1959, 82:70-7.
• [32]Brestel EP: Co-oxidation of luminol and hydrogen peroxide. Implications for neutrophil chemiluminecence. Biochem Biophys Res Commun 1985, 126:482-8.
• [33]Vanholder R, Glorieux G, Lameire N: European Uremic Toxin Work Group. Uraemic toxins and cardiovascular disease. Nephrol Dial Transplant 2003, 18:463-6.
• [34]Nieto FJ, Iribarren C, Gross MD, Comstock GW, Cutler RG: Uric acid and serum antioxidant capacity: a reaction to atherosclerosis? Atherosclerosis 2000, 148:131-9.
• [35]Miyamoto Y, Iwao Y, Tasaki Y, Sato K, Ishima Y, Watanabe H, et al.: The uremic solute indoxyl sulfate acts as an antioxidant against superoxide anion radicals under normal-physiological conditions. FEBS Lett 2010, 584:2816-20.
• [36]Budavari S, O’Neil MJ, Smith A, Heckelman PE: The Merck Index (an encyclopedia of chemicals, drugs, and biologicals). 14th edition. Merck, New Jersey; 2006.
• [37]Lussignoli S, Fraccaroli M, Andrioli G, Brocco G, Bellavite P: A microplate based colorimetric assay of the total peroxyl radical trapping capability of human plasma. Anal Biochem 1999, 269:38-44.
• [38]Mello LD, Kubota LT: Biosensors as a tool for the antioxidant status evaluation. Talanta 2007, 72:335-48.
• [39]Vellosa JCR, Khalil NM, Gutierres VO, Santos VAFFM, Furlan M, Brunetti IL, et al.: Salacia campestris root bark extract: peroxidase inhibition, antioxidant and antiradical profile. Braz J Pharm Sci 2009, 45:99-107.
• [40]Gülçin I: Comparison of in vitro antioxidant and antiradical activities of L- tyrosine and L-Dopa. Amino Acids 2007, 32:431-8.
• [41]Chung Y, Wang H, El-Shazly M, Leu YL, Cheng MC, Lee CL, et al.: Antioxidant and tyrosinase inhibitory constituents from a desugared sugar cane extract, a byproduct of sugar production. J Agric Food Chem 2011, 59:9219-25.
• [42]Bianchi PD, Barp J, Thomé FS, Belló-Klein A: Efeito de uma sessão de hemodiálise sobre o estresse oxidativo sistêmico de pacientes renais crônicos terminais. J Bras Nefrol 2009, 31:175-82.
• [43]Rutgers A, Heeringa P, Kooman JP, Van der Sande FM, Tervaert WC: Peripheral blood myeloperoxidase activity increases during hemodialysis. Kidney Int 2003, 64:760-2.
• [44]Capeillere-Blandin C, Gausson V, Nguyen AT, Descamps-Latscha B, Drueke T, Witko-Sarsat V: Respective role of uraemic toxins and myeloperoxidase in the uraemic state. Nephrol Dial Transplant 2006, 21:1555-63.
• [45]Marsche G, Frank S, Hrzenjak A, Holzer M, Dirnberger S, Wadsack C, et al.: Plasma-advanced oxidation protein products are potent high-density lipoprotein receptor antagonists in vivo. Circ Res 2009, 104:750-7.
• [46]Kitabayashi C, Naruko T, Sugioka K, Yunoki K, Nakagawa M, Inaba M, et al.: Positive association between plasma levels of oxidized low-density lipoprotein and myeloperoxidase after hemodialysis in patients with diabetic end-stage renal disease. Hemodial Int 2013, 17:557-67.
• [47]Cadenas E, Davies KJ: Mitochondrial free radical generation, oxidative stress, and aging. Free Rad Biol Med 2000, 29:222-30.
• [48]Schmidt RJ, Yokota S, Tracy TS, Sorkin MI, Baylis C: Nitric oxide production is low in end-stage renal disease patients on peritoneal dialysis. Am J Physiol 1999, 276:794-7.
• [49]Baylis C: Arginine, arginine analogs and nitric oxide production in chronic kidney disease. Nat Clin Pract Nephrol 2006, 2:209-20.
• [50]Barreiros ALBS, David JM, David JP: Estresse oxidativo: relação entre geração de espécies reativas e defesa do organismo. Quim Nova 2006, 29:113-23.
• [51]Ak T, Gülçin I: Antioxidant and radical scavenging properties of curcumin. Chem Biol Interact 2008, 174:27-37.
• [52]Ujhelyi L, Balla G, Jeney V, Varga Z, Nagy E, Vercellotti GM, et al.: Response to p-Cresol for better or worse: But what are we measuring? Kidney Int 2006, 70:232-3.
• [53]Sautin YY, Johnson RJ: Uric acid: the oxidant – antioxidant paradox. Nucleos Nucleot Nucl 2008, 27:608-19.
• [54]Praschberger M, Hermann M, Wanner J, Jirovetz L, Exner M, Kapiotis S, et al.: The uremic toxin indoxyl sulfate acts as a pro- or antioxidant on LDL oxidation. Free Radic Res 2014, 6:641-8.
• [55]Llesuy SF, Milei J, Flecha BSG, Boveris A: Myocardial damage induced by doxorubicins: hydroperoxide-initiated chemiluminescence and morphology. Free Radic Biol Med 1990, 8:259-64.
• [56]Gonzalez Flecha B, Llesuy S, Boveris A: Hydroperoxide-initiated chemiluminescence: an assay for oxidative stress in biopsies of heart, liver, and muscle. Free Radic Biol Med 1991, 10:93-100.
• [57]Noguer M, Cerezo AB, Moyá ML, Troncoso AM, García-Parrilla MC: Synergism effect between phenolic metabolites and endogenous antioxidants in terms of antioxidant activity. ACES 2014, 4:258-65.
• [58]Ordoudi SA, Tsimidou MZ: Crocin Bleaching Assay (CBA) in structure-radical scavenging activity studies of selected phenolic compounds. J Agric Food Chem 2006, 54:9347-56.
• [59]MacNnamara PJ, Lalka D, Gibaldi M: Endogenous accumulation products and serum protein binding in uremia. J Lab Clin Med 1981, 98:730-40.
• [60]Simenhoff ML, Asatoor AM, Milne MD, Zilva JF: Retention of aliphatic amines in uraemia. Clin Sci 1963, 25:65-77.
• [61]Vanholder RC, Desmet RV, Ringoir SM: Assessment of urea and other uremic markers for quantification of dialysis efficacy. Clin Chem 1992, 38:1429-36.
• [62]Roberts WL, McMillin GA, Burtis CA, Bruns DE. Appendix. In: Burtis CA, Ashwood ER, Bruns DE, editors. Tietz textbook of clinical chemistry and molecular diagnostics. St. Louis, Missouri: Elsevier; 2006.p. 2252-2302.
• [63]Niwa T, Maeda K, Ohki T, Saito A, Kobayashi K: Gas chromatographic-mass spectrometric analysis for phenolin uremis serum. Clin Chim Acta 1981, 110:51-7.
• [64]Matsumoto M, Kishikawa H, Mori A: Guanidino compounds in the sera of uremic patients and in the sera and brain of experimental uremic rabbits. Biochem Med 1976, 16:1-8.
• [65]Farrel PC, Gotch FA, Peters JH, Berridge BJ Jr, Lam M: Binding of hippurate in normal plasma and in uremic plasma pre - and post-dialysis. Nephron 1978, 20:40.
• [66]Eksborg S, Persson BA, Allgen LG, Bergström J, Zimmerman L, Fürst P: A seletive method for determination of methil-guanidine in biological fluids. Its application in normal subjects and uremic patients. Clin Chim Acta 1978, 82:141-50.
• [67]Wengle B, Hellstrom K: Volatile phenols in serum of uremic patients. Clin Sci 1972, 43:493-8.
• [68]Schoots AC, Peeters JAG, Gerlag PGG: Effect of hemodialysis on serum concentration of HPLC-analyzed accumulating solutes in uremia. Nephron 1989, 53:208-17.
• [69]Salisbury PF, Dunn MS, Murphy EA: Apparent free aminoacids in deproteinized plasma of normal and uremic persons. J Clin Invest 1957, 36:1227-32.
• [70]Vanholder R, Hoenich N, Ringoir S: Adequacy studies of fistula single-needle dialysis. Am J Kidney Dis 1987, 10:417-26.