Skip to main content

Advertisement

Log in

Intravenous glutathione prevents renal oxidative stress after coronary angiography more effectively than oral N-acetylcysteine

  • Original Article
  • Published:
Heart and Vessels Aims and scope Submit manuscript

Abstract

This study proposes the intravenous administration of glutathione (GSH) as a novel strategy to prevent contrast medium-induced renal oxidative stress. Renal oxidative stress is a critical cause of contrast-induced nephropathy (CIN). Recent reports have described that N-acetylcysteine (NAC) may prevent CIN by scavenging reactive oxygen species in the kidney. Twenty-one patients with reduced renal function who underwent coronary angiography (CAG) were equally assigned to the control, NAC and GSH (100 mg/min for 30 min before CAG) groups. CIN occurred in two patients, one in the control and the other in the NAC group. In the control group, the urinary lipid hydroperoxides (LOOHs) increased to 299.5 ± 94.4% of the baseline at 2 h after CAG (mean ± SE, p < 0.01). The increase in LOOHs was completely abolished in the GSH group (5.5 ± 8.8%, p = ns), but not in the NAC group (196.8 ± 81.3%, p < 0.05). In the control group, the serum GSH level fell by 9.4 ± 2.3% at 2 h after CAG (p < 0.01). The decrease was prevented in the GSH group (−1.8 ± 8.5%, p = ns), but not in the NAC group (−10.0 ± 3.3%, p < 0.05). The renal damage by contrast medium-induced oxidative stress occurs soon after CAG, and intravenous GSH is more effective in preventing the oxidative stress than oral NAC. This advantage may make GSH a potentially more effective therapeutic strategy against CIN.

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. Kimura T, Morimoto T, Furukawa Y, Kita T (2009) Incidence of and risk factors for contrast-induced nephropathy after cardiac catheterization in Japanese patients. Circ J 73:1518–1522

    Article  PubMed  Google Scholar 

  2. Freeman RV, O’Donnell M, Share D, Meengs WL, Kline-Rogers E, Clark VL, DeFranco AC, Eagle KA, McGinnity JG, Patel K, Maxwell-Eward A, Bondie D, Moscucci M (2002) Nephropathy requiring dialysis after percutaneous coronary intervention and the critical role of an adjusted contrast dose. Am J Cardiol 90:1068–1073

    Article  PubMed  Google Scholar 

  3. Murphy SW, Barrett BJ, Parfrey PS (2000) Contrast nephropathy. J Am Soc Nephrol 11:177–182

    PubMed  CAS  Google Scholar 

  4. Parfrey PS, Griffiths SM, Barrett BJ, Paul MD, Genge M, Withers J, Farid N, McManamon PJ (1989) Contrast material-induced renal failure in patients with diabetes mellitus, renal insufficiency, or both. A prospective controlled study. N Engl J Med 320:143–149

    Article  PubMed  CAS  Google Scholar 

  5. Rich MW, Crecelius CA (1990) Incidence, risk factors, and clinical course of acute renal insufficiency after cardiac catheterization in patients 70 years of age or older. A prospective study. Arch Intern Med 150:1237–1242

    Article  PubMed  CAS  Google Scholar 

  6. Tepel M, Aspelin P, Lameire N (2006) Contrast-induced nephropathy: a clinical and evidence-based approach. Circulation 113:1799–1806

    Article  PubMed  Google Scholar 

  7. Fishbane S, Durham JH, Marzo K, Rudnik M (2004) N-acetylcysteine in the prevention of radiocontrast-induced nephropathy. J Am Soc Nephrol 15:251–260

    Article  PubMed  CAS  Google Scholar 

  8. Gleeson TG, Bulugahapitiya S (2004) Contrast-induced nephropathy. Am J Roentgenol 183:1673–1689

    Google Scholar 

  9. Maeder M, Klein M, Fehr T, Rickli H (2004) Contrast nephropathy: review focusing on prevention. J Am Coll Cardiol 44:1763–1771

    Article  PubMed  Google Scholar 

  10. McCullough PA, Wolyn R, Rocher LL, Levin RN, O’Neill WW (1997) Acute renal failure after coronary intervention: incidence, risk factors, and relationship to mortality. Am J Med 103:368–375

    Article  PubMed  CAS  Google Scholar 

  11. Rihal CS, Textor SC, Grill DE, Berger PB, Ting HH, Best PJ, Singh M, Bell MR, Barsness GW, Mathew V, Garratt KN, Holmes DR Jr (2002) Incidence and prognostic importance of acute renal failure after percutaneous coronary intervention. Circulation 105:2259–2264

    Article  PubMed  Google Scholar 

  12. Bakris GL, Lass N, Gaber AO, Jones JD, Burnett JC Jr (1990) Radiocontrast medium-induced declines in renal function: a role for oxygen free radicals. Am J Physiol 258:F115–F120

    PubMed  CAS  Google Scholar 

  13. Yoshioka T, Fogo A, Beckman JK (1992) Reduced activity of antioxidant enzymes underlies contrast media-induced renal injury in volume depletion. Kidney Int 41:1008–1015

    Article  PubMed  CAS  Google Scholar 

  14. Detrenis S, Meschi M, Musini S, Savazzi G (2005) Lights and shadows on the pathogenesis of contrast-induced nephropathy: state of the art. Nephrol Dial Transpl 20:1542–1550

    Article  Google Scholar 

  15. Persson PB, Hansell P, Lis P (2005) Pathophysiology of contrast medium-induced nephropathy. Kidney Int 68:14–22

    Article  PubMed  CAS  Google Scholar 

  16. Marenzi G, Assanelli E, Marana I, Lauri G, Campodonico J, Grazi M, De Metrio M, Galli S, Fabbiocchi F, Montorsi P, Veglia F, Bartorelli AL (2006) N-acetylcysteine and contrast-induced nephropathy in primary angioplasty. N Engl J Med 354:2773–2782

    Article  PubMed  CAS  Google Scholar 

  17. Abbott WA, Bridges RJ, Meister A (1984) Extracellular metabolism of glutathione accounts for its disappearance from the basolateral circulation of the kidneys. J Biol Chem 259:15393–15400

    PubMed  CAS  Google Scholar 

  18. Lash LH (2005) Role of glutathione transport processes in kidney function. Toxicol Appl Pharmacol 204:329–342

    Article  PubMed  CAS  Google Scholar 

  19. Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16:31–41

    Article  PubMed  CAS  Google Scholar 

  20. Aebi S, Assereto R, Lauterburg BH (1991) High-dose intravenous glutathione in man. Pharmacokinetics and effects on cyst(e)ine in plasma and urine. Eur J Clin Invest 21:103–110

    Article  PubMed  CAS  Google Scholar 

  21. Oriana S, Böhm S, Spatti G, Zunino F, Di Re F (1987) A preliminary clinical experience with reduced glutathione as protector against cisplatin-toxicity. Tumori 73:337–340

    PubMed  CAS  Google Scholar 

  22. Girotti AW (1998) Lipid hydroperoxide generation, turnover, and effector action in biological systems. J Lipid Res 39:1529–1542

    PubMed  CAS  Google Scholar 

  23. Kato K, Sato N, Yamamoto T, Iwasaki YK, Tanaka K, Mizuno K (2008) Valuable markers for contrast-induced nephropathy in patients undergoing cardiac catheterization. Circ J 72:1499–1505

    Article  PubMed  CAS  Google Scholar 

  24. Zhou H, Kato A, Miyaji T, Yasuda H, Fujigaki Y, Yamamoto T, Yonemura K, Takebayashi S, Mineta H, Hishida A (2006) Urinary marker for oxidative stress in kidneys in cisplatin-induced acute renal failure in rats. Nephrol Dial Transpl 21:616–623

    Article  CAS  Google Scholar 

  25. Yenicerioglu Y, Yilmaz O, Sarioglu S, Ormen M, Akan P, Celik A, Camsari T (2006) Effects of N-acetylcysteine on radiocontrast nephropathy in rats. Scand J Urol Nephrol 40:63–69

    Article  PubMed  CAS  Google Scholar 

  26. Trivedi HS, Moore H, Nasr S, Aggarwal K, Agrawal A, Goel P, Hewett J (2003) A randomized prospective trial to assess the role of saline hydration on the development of contrast nephrotoxicity. Nephron Clin Pract 93:29–34

    Article  Google Scholar 

  27. Solomon RJ, Natarajan MK, Doucet S, Sharma SK, Staniloae CS, Katholi RE, Gelormini JL, Labinaz M, Moreyra AE, Investigators of the CARE Study (2007) Cardiac Angiography in Renally Impaired Patients (CARE) study: a randomized double-blind trial of contrast-induced nephropathy in patients with chronic kidney disease. Circulation 115:3189–3196

    Article  PubMed  Google Scholar 

  28. Thomsen HS, Morcos SK, Erley CM, Grazioloi L, Bonomo L, Ni Z (2008) The ACTIVE Trial: comparison of the effects on renal function of iomeprol-400 and idoixanol-320 in patients with chronic kidney disease undergoing abdominal computed tomography. Invest Radiol 43:170–178

    Article  PubMed  CAS  Google Scholar 

  29. Murphy MB, Murray C, Shorten GD (2001) Fenoldopam: a selective peripheral dopamine-receptor agonist for the treatment of severe hypertension. N Engl J Med 345:1548–1557

    Article  PubMed  CAS  Google Scholar 

  30. Briguori C, Colombo A, Airoldi F, Violante A, Castelli A, Balestrieri P, Paolo Elia P, Golia B, Lepore S, Riviezzo G, Scarpato P, Librera M, Focaccio A, Ricciardelli B (2004) N-acetylcysteine versus fenoldopam mesylate to prevent contrast agent-associated nephrotoxicity. J Am Coll Cardiol 44:762–765

    Article  PubMed  CAS  Google Scholar 

  31. Sankar D, Navaneethan SD, Singh S, Appasamy S, Wing RE, Sehgal AR (2009) Sodium bicarbonate therapy for prevention of contrast-induced nephropathy: a systematic review and meta-analysis. Am J Kidney Dis 53:617–627

    Article  Google Scholar 

  32. Birck R, Krzossok S, Markowetz F, Schnülle P, van der Woude FJ, Braun C (2003) Acetylcysteine for prevention of contrast nephropathy: meta-analysis. Lancet 362:598–603

    Article  PubMed  CAS  Google Scholar 

  33. Gomes VO, Poli de Figueredo CE, Caramori P, Lasevitch R, Bodanese LC, Araújo A, Röedel AP, Caramori AP, Brito FS Jr, Bezerra HG, Nery P, Brizolara A (2005) N-acetylcysteine does not prevent contrast induced nephropathy after cardiac catheterisation with an ionic low osmolality contrast medium: a multicentre clinical trial. Heart 91:774–778

    Article  PubMed  CAS  Google Scholar 

  34. Oldemeyer JB, Biddle WP, Wurdeman RL, Mooss AN, Cichowski E, Hilleman DE (2003) Acetylcysteine in the prevention of contrast-induced nephropathy after coronary angiography. Am Heart J 146:E23

    Article  PubMed  Google Scholar 

  35. Harada D, Naito S, Kawauchi Y, Ishikawa K, Koshitani O, Hiraoka I, Otagiri M (2001) Determination of reduced, protein-unbound, and total concentrations of N-acetyl-l-cysteine and l-cysteine in rat plasma by postcolumn ligand substitution high-performance liquid chromatography. Anal Biochem 290:251–259

    Article  PubMed  CAS  Google Scholar 

  36. Olsson B, Johansson M, Gabrielsson J, Bolme P (1988) Pharmacokinetics and bioavailability of reduced and oxidized N-acetylcysteine. Eur J Clin Pharmacol 34:77–82

    Article  PubMed  CAS  Google Scholar 

  37. Scaduto RC Jr, Gattone VH 2nd, Martin LF, Yang HC (1991) Elevation of renal glutathione enhances ischemic injury. Ren Physiol Biochem 14:259–270

    PubMed  CAS  Google Scholar 

  38. Prasad A, Andrews NP, Padder FA, Husain M, Quyyumi AA (1999) Glutathione reverses endothelial dysfunction and improves nitric oxide bioavailability. J Am Coll Cardiol 34:507–514

    Article  PubMed  CAS  Google Scholar 

  39. Zunino F, Pratesi G, Micheloni A, Cavalletti E, Sala F, Tofanetti O (1989) Protective effect of reduced glutathione against cisplatin-induced renal and systemic toxicity and its influence on the therapeutic activity of the antitumor drug. Chem Biol Interact 70:89–101

    Article  PubMed  CAS  Google Scholar 

  40. Tofanetti O, Cavalletti E, Besati A, Pratesi G, Pezzoni G, Zunino F (1985) Prevention of cyclophosphamide-induced urotoxicity by reduced glutathione and its effect on acute toxicity and antitumor activity of the alkylating agent. Cancer Chemother Pharmacol 14:188–193

    Article  PubMed  CAS  Google Scholar 

  41. Zager RA, Johnson AC, Hanson SY (2003) Radiographic contrast media-induced tubular injury: evaluation of oxidant stress and plasma membrane integrity. Kidney Int 64:128–139

    Article  PubMed  CAS  Google Scholar 

  42. Bohm S, Oriana S, Spatti G, Di Re F, Breasciani G, Pirovano C, Grosso I, Martini C, Caraceni A, Pilotti S, Zunino F (1999) Dose intensification of platinum compounds with glutathione protection as induction chemotherapy for advanced ovarian carcinoma. Oncology 57:115–120

    Google Scholar 

  43. Patti G, Nusca A, Chello M, Pasceri V, D’Ambrosio A, Vetrovec GW, Di Sciascio G (2008) Usefulness of statin pretreatment to prevent contrast-induced nephropathy and to improve long-term outcome in patients undergoing percutaneous coronary intervention. Am J Cardiol 101:279–285

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hiroshi Satoh.

Appendix

Appendix

The molecular weights of NAC (C5H9NO3S) and GSH (C10H17N3O6S) are 163.2 and 307.4, respectively. The bioavailability of NAC has been shown to be 3.4–19.8%, implying that approximately 90% of NAC degenerates to cysteine, which can be synthesized to GSH in the liver [35, 36]. Since the total amount of NAC administered during this study was 2,820 mg (1,410 mg a day for 2 days), it is equivalent to 4,780 mg of GSH (2,820 mg/163.2 × 307.4 × 0.9).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Saitoh, T., Satoh, H., Nobuhara, M. et al. Intravenous glutathione prevents renal oxidative stress after coronary angiography more effectively than oral N-acetylcysteine. Heart Vessels 26, 465–472 (2011). https://doi.org/10.1007/s00380-010-0078-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00380-010-0078-0

Keywords

Navigation