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Gender differences in oxidative and nitrosative stress parameters in kidney transplant patients on tacrolimus-based immunosuppression

  • Nephrology - Original Paper
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Abstract

Background

Cardiovascular (CV) morbidity and mortality rates are still higher after kidney transplantation than in general population. It is known that oxidative and nitrosative stress may contribute to the progress of CV disease in a post-transplant period, but still gender aspect has not been elucidated completely. The aim of this study was to analyze the gender differences in the oxidative and nitrosative stress parameters, as well as asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) levels among kidney transplant patients on tacrolimus-based immunosuppression.

Methods

Our research included 35 patients (20 men and 15 women) with renal transplant and 25 healthy volunteers. Patients were on chronic immunosuppressive regimen, which included tacrolimus, mycophenolate mofetil and prednisone. In order to estimate oxidative and nitrosative stress, we determined plasma levels of thiobarbituric acid-reactive substances (TBARS), activity of catalase (CAT), levels of total (protein and non-protein) sulfhydryl (SH) groups, advanced oxidation protein products (AOPP), ADMA and SDMA, as well as nitrite/nitrate (NOx) ratio.

Results

TBARS, CAT and SH in plasma were significantly higher in male patients than in female patients (p < 0.05, p < 0.01 and p < 0.05, respectively). There were no gender-dependent differences in AOPP, ADMA, SDMA and NOx in kidney transplant patients. Correlation analysis, Pearson and Spearman, showed significant correlations between tested oxidative and nitrosative stress parameters in male kidney transplant patients. Alternatively, in female patients, there were no significant correlations between tested parameters.

Conclusion

Our findings show that men might be more prone to oxidative damage than women. ADMA, the proven marker of CV morbidity and mortality, may be more significant in male kidney transplant patients concerning oxidative stress control of its level and function.

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References

  1. Bestard O, Cruzado JM, la Franquesa M et al (2010) Biomarkers in renal transplantation. Curr Opin Organ Transplant 15:467–473

    Article  PubMed  Google Scholar 

  2. Nafar M, Sahraei Z, Salamzadeh J et al (2011) Oxidative stress in kidney transplantation: causes, consequences, and potential treatment. Iran J Kidney Dis 5:357–372

    PubMed  Google Scholar 

  3. Ueda S, Yamagishi S, Matsumoto Y et al (2007) Asymmetric dimethylarginine (ADMA) is a novel emerging risk factor for cardiovascular disease and the development of renal injury in chronic kidney disease. Clin Exp Nephrol 11:115–121

    Article  CAS  PubMed  Google Scholar 

  4. Ignjatovic AM, Cvetkovic TP, Pavlovic RM et al (2013) Endothelial dysfunction, inflammation and malnutrition markers as predictors of mortality in dialysis patients: multimarker approach. Int Urol Nephrol doi:10.1007/s11255-013-0439-6

  5. Ji H, Zheng W, Menini S et al (2007) Female protection in progressive renal disease is associated with estradiol attenuation of superoxide production. Gend Med 4:56–71

    Article  PubMed  Google Scholar 

  6. Kielstein JT, Zoccali C (2005) Asymmetric dimethylarginine: a cardiovascular risk factor and a uremic toxin coming of age? Am J Kidney Dis 46:186–202

    Article  CAS  PubMed  Google Scholar 

  7. Kielstein JT, Impraim B, Simmel S et al (2004) Cardiovascular effects of systemic nitric oxide synthase inhibition with asymmetrical dimethylarginine in humans. Circulation 109:172–177

    Article  CAS  PubMed  Google Scholar 

  8. Beckman JS, Koppenol WH (1996) Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol 271:C1424–C1437

    CAS  PubMed  Google Scholar 

  9. Silbiger S, Neugarten J (2008) Gender and human chronic renal disease. Gend Med 5 Suppl A: S3–S10

    Google Scholar 

  10. Andreeva IL, Kožemjakin AL, Kiškun AA (1988) Modification of the method of measurement of lipid peroxides in test with thiobarbituric acid (in Russian). Lab Delo 11:41–43

    PubMed  Google Scholar 

  11. Goth L (1991) Serum catalase: reversibly formed charge isoform of erythrocyte catalase. Clin Chem 37:2043–2204

    CAS  PubMed  Google Scholar 

  12. Hu ML (1994) Measurement of protein thiol groups and glutathione in plasma. In: Abelson J, Simon MI (eds) Methods in enzymology. Academic Press, California, pp 380–382

    Google Scholar 

  13. Sedlak J, Lindsday R (1968) Estimation of total protein bound and non-protein sulphydryl groups in tissue with Ellman’s reagent. Anal Biochem 25:192–205

    Article  CAS  PubMed  Google Scholar 

  14. Witko-Sarsat V, Friedlander M, Capeillere-Blandin C et al (1996) Advanced oxidation protein products as a novel marker of oxidative stress in uremia. Kid Int 49:1304–1305

    Article  CAS  Google Scholar 

  15. Navaro-Gonzalvez JA, Garcia-Benayas C, Arenas J (1998) Semiautomated measurement of nitrate in biological fluids. Clin Chem 44:679–681

    Google Scholar 

  16. Paroni R, Fermo I, Fiorina P et al (2005) Determination of asymmetric and symmetric dimethylarginines in plasma of hyperhomocysteinemic subjects. Amino Acid 28:389–394

    Article  CAS  Google Scholar 

  17. Ruiz MC, Medina A, Moreno JM et al (2005) Relationship between oxidative stress parameters and atherosclerotic signs in the carotid artery of stable renal transplant patients. Transplant Proc 37:3796–3798

    Article  CAS  PubMed  Google Scholar 

  18. Neugarten J, Acharya A, Silbiger SR (2000) Effect of gender on the progression of nondiabetic renal disease: a meta-analysis. J Am Soc Nephrol 11:319–329

    CAS  PubMed  Google Scholar 

  19. Vural A, Yilmaz MI, Caglar K et al (2005) Assessment of oxidative stress in the early posttransplant period: comparison of cyclosporine a and tacrolimus-based regimens. Am J Nephrol 25:250–255

    Article  CAS  PubMed  Google Scholar 

  20. Chrzanowska M, Kamińska J, Głyda M et al (2010) Antioxidant capacity in renal transplant patients. Pharmazie 65:363–366

    CAS  PubMed  Google Scholar 

  21. Perrea DN, Moulakakis KG, Poulakou MV et al (2006) Correlation between oxidative stress and immunosuppressive therapy in renal transplant recipients with an uneventful postoperative course and stable renal function. Int Urol Nephrol 38:343–348

    Article  CAS  PubMed  Google Scholar 

  22. Zadrazil J, Strebl P, Krejcí K et al (2010) Effect of different calcineurin inhibitors on AOPP and TAS after kidney transplantation. Clin Biochem 43:559–565

    Article  CAS  PubMed  Google Scholar 

  23. Viña J, Sastre J, Pallardó FV et al (2006) Role of mitochondrial oxidative stress to explain the different longevity between genders: protective effect of estrogens. Free Radic Res 40:1359–1365

    Article  PubMed  Google Scholar 

  24. Actis-Goretta L, Carrasquedo F, Fraga CG (2004) The regular supplementation with an antioxidant mixture decreases oxidative stress in healthy humans gender effect. Clin Chim Acta 349:97–103

    Article  CAS  PubMed  Google Scholar 

  25. Roehrs M, Valentini J, Paniz C et al (2011) The relationships between exogenous and endogenous antioxidants with the lipid profile and oxidative damage in hemodialysis patients. BMC Nephrol 12:59

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Perianayagam MC, Liangos O, Kolyada AY et al (2007) NADPH oxidase p22phox and catalase gene variants are associated with biomarkers of oxidative stress and adverse outcomes in acute renal failure. J Am Soc Nephrol 18:255–263

    Article  CAS  PubMed  Google Scholar 

  27. Himmelfarb J, McMonagle E, McMenamin E (2000) Plasma protein thiol oxidation and carbonyl formation in chronic renal failure. Kidney Int 58:2571–2578

    Article  CAS  PubMed  Google Scholar 

  28. Cvetkovic T, Pavlovic R, Djordjevic VB et al (2012) Dimethylarginine—biomarkers in progression of kidney disease. J Med Biochem 31:301–309

    Article  CAS  Google Scholar 

  29. Böger RH (2004) Asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, explains the “l-arginine paradox” and acts as a novel cardiovascular risk factor. J Nutr 134(Suppl 10):2842S–2847S

    PubMed  Google Scholar 

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Acknowledgments

This study was supported by grant of Ministry of Science and Technological Development of Serbia—Project Number 41018.

Conflict of interest

The results presented in this paper have not been published previously in whole or part, except in abstract form. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

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Correspondence to Tatjana P. Cvetkovic.

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Cvetkovic, T.P., Stefanovic, N.Z., Velickovic-Radovanovic, R.M. et al. Gender differences in oxidative and nitrosative stress parameters in kidney transplant patients on tacrolimus-based immunosuppression. Int Urol Nephrol 46, 1217–1224 (2014). https://doi.org/10.1007/s11255-013-0577-x

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  • DOI: https://doi.org/10.1007/s11255-013-0577-x

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